{"id":1111,"date":"2017-03-02T21:31:22","date_gmt":"2017-03-02T21:31:22","guid":{"rendered":"https:\/\/www.progeriaresearch.org\/?page_id=1111"},"modified":"2025-05-13T12:35:59","modified_gmt":"2025-05-13T16:35:59","slug":"grants-funded","status":"publish","type":"page","link":"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/","title":{"rendered":"Subventions financ\u00e9es"},"content":{"rendered":"<p>[et_pb_section fb_built=\u201d1\u2033 fullwidth=\u201don\u201d disabled_on=\u201doff|off|off\u201d _builder_version=\u201d4.16\u2033 border_width_bottom=\u201d55px\u201d border_color_bottom=\u201d#29327a\u201d locked=\u201doff\u201d global_colors_info=\u201d{}\u201d][et_pb_fullwidth_header _builder_version=\u201d4.16\u2033 title_font_size=\u201d55\u2033 background_color=\u201d#29327a\u201d background_image=\u201dhttps:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2020\/12\/Alexandra_1920x687.jpg\u201d background_position=\u201dcenter_left\u201d custom_padding=\u201d11.5vw||11.5vw|\u201d custom_padding_tablet=\u201d\u201d custom_padding_phone=\u201d|56px||\u201d custom_padding_last_edited=\u201dsur|bureau\u201d title_font_size_tablet=\u201d45px\u201d title_font_size_phone=\u201d40px\u201d title_font_size_last_edited=\u201dsur|t\u00e9l\u00e9phone\u201d z_index_tablet=\u201d500\u2033 custom_css_main_element=\u201dbackground-position: center 18% !important;\u201d global_colors_info=\u201d{}\u201d]<\/p>\n<h1>Subventions financ\u00e9es<\/h1>\n<p>&nbsp;<br \/>\n[\/et_pb_fullwidth_header][\/et_pb_section][et_pb_section fb_built=&#8221;1&#8243; use_custom_gutter=&#8221;on&#8221; gutter_width=&#8221;1&#8243; specialty=&#8221;on&#8221; padding_left_1=&#8221;35px&#8221; padding_left_2=&#8221;35px&#8221; padding_2_tablet=&#8221;|||0px&#8221; padding_2_phone=&#8221;|||0px&#8221; padding_2_last_edited=&#8221;on|desktop&#8221; module_class_1=&#8221;sidebar-secondary-nav&#8221; module_class=&#8221;handprint-bg&#8221; _builder_version=&#8221;4.16&#8243; background_image=&#8221;https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2019\/04\/blue-handprint-only.png&#8221; parallax=&#8221;on&#8221; parallax_method=&#8221;off&#8221; inner_width=&#8221;100%&#8221; inner_max_width=&#8221;100%&#8221; custom_padding=&#8221;0|0px|54px|0px|false|false&#8221; z_index_tablet=&#8221;500&#8243; border_width_top=&#8221;10px&#8221; border_color_top=&#8221;#8fd2ed&#8221; use_custom_width=&#8221;on&#8221; width_unit=&#8221;off&#8221; custom_width_percent=&#8221;100%&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_column type=&#8221;1_4&#8243; _builder_version=&#8221;4.16&#8243; custom_padding=&#8221;|||&#8221; global_colors_info=&#8221;{}&#8221; custom_padding__hover=&#8221;|||&#8221;][et_pb_sidebar area=&#8221;et_pb_widget_area_15&#8243; disabled_on=&#8221;on|on|off&#8221; module_class=&#8221;subpage-sidebars&#8221; _builder_version=&#8221;4.16&#8243; animation_style=&#8221;fade&#8221; z_index_tablet=&#8221;500&#8243; border_width_right=&#8221;5px&#8221; locked=&#8221;off&#8221; global_colors_info=&#8221;{}&#8221;][\/et_pb_sidebar][\/et_pb_column][et_pb_column type=&#8221;3_4&#8243; specialty_columns=&#8221;3&#8243; _builder_version=&#8221;4.16&#8243; custom_padding=&#8221;|||&#8221; global_colors_info=&#8221;{}&#8221; custom_padding__hover=&#8221;|||&#8221;][et_pb_row_inner custom_padding_last_edited=&#8221;on|phone&#8221; _builder_version=&#8221;4.16&#8243; custom_padding=&#8221;39.4375px|35px|35px||false|false&#8221; custom_padding_tablet=&#8221;|35px||35px||true&#8221; custom_padding_phone=&#8221;&#8221; animation_direction=&#8221;top&#8221; global_colors_info=&#8221;{}&#8221;][et_pb_column_inner saved_specialty_column_type=&#8221;3_4&#8243; _builder_version=&#8221;4.16&#8243; custom_padding=&#8221;|||&#8221; global_colors_info=&#8221;{}&#8221; custom_padding__hover=&#8221;|||&#8221;][et_pb_text admin_label=&#8221;anchor list&#8221; _builder_version=&#8221;4.27.0&#8243; background_size=&#8221;initial&#8221; background_position=&#8221;top_left&#8221; background_repeat=&#8221;repeat&#8221; z_index_tablet=&#8221;500&#8243; border_width_bottom=&#8221;10px&#8221; border_color_bottom=&#8221;#8fd2ed&#8221; global_colors_info=&#8221;{}&#8221;]<\/p>\n<p><span>Depuis sa cr\u00e9ation en 1999, le PRF a fourni plus de 14,9 millions de livres sterling pour financer 85 subventions pour des projets de recherche li\u00e9s \u00e0 la prog\u00e9ria men\u00e9s dans 18 \u00c9tats et 14 autres pays !<\/span><\/p>\n<p><strong>Les subventions que nous avons financ\u00e9es et les croquis biologiques des chercheurs<\/strong><strong><\/strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2022-LA\"><\/a><\/p>\n<p><strong><\/strong><\/p>\n<ul>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2023-RVB\"><b><span>Mars 2023<\/span><\/b><\/a><span><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2022-RVB\">:<\/a> <\/span><\/strong>\u00e0 <span lang=\"ES\">Ricardo<\/span> Villa-Bellosta, Saint-Jacques-de-Compostelle, Espagne. \u00ab Progeria et calcification vasculaire : r\u00e9gime et traitements. \u00bb<strong><\/strong><\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2022-LA\"><\/a><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2022-SOG\"><strong>Novembre 2022 : <\/strong><\/a>\u00e0 Silvia Ortega Gutierrez, Universit\u00e9 Complutense, Madrid Espagne<br \/>\u00ab La r\u00e9duction des niveaux de prog\u00e9rine par de petites mol\u00e9cules comme nouvelle approche pour le traitement de la prog\u00e9ria \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2022-LA\"><strong>Octobre 2022 : <\/strong><\/a>\u00e0 Laurence Arbibe, Institut Necker-Enfants Malades (INEM), Paris, France<br \/>\u00ab D\u00e9crypter le vieillissement intestinal acc\u00e9l\u00e9r\u00e9 dans la physiopathologie du syndrome de Guillain-Barr\u00e9 : une approche int\u00e9grative \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2022-1KD\"><strong>Janvier 2022 :<\/strong><\/a> \u00e0 Karima Djabali, Universit\u00e9 technique de Munich, Munich, Allemagne.<br \/>\u00ab Traitement du syndrome de Hutchinson-Gilford Progeria avec deux m\u00e9dicaments approuv\u00e9s par la FDA combin\u00e9s \u2014 Lonafarnib et Baricitinib, inhibiteurs sp\u00e9cifiques de la farn\u00e9syltransf\u00e9rase et de la kinase JAK1\/2 respectivement \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2021-7\"><strong>Juillet 2021 :<\/strong><\/a> \u00e0 Chiara Lanzuolo, Instituto Nazionale Genetica Molecolare, Milan, Italie.<br \/>\u00ab Suivi de la r\u00e9cup\u00e9ration de la structure et de la fonction du g\u00e9nome suite \u00e0 des traitements pharmacologiques dans le syndrome de Hutchinson Gilford Progeria \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2021-7MC\"><strong>Juillet 2021 :<\/strong><\/a> \u00e0 Mario Cordero, Institut de recherche et d&#039;innovation biom\u00e9dicale de Cadix (INIBICA), Cadix, Espagne. \u00ab Inhibition de l&#039;inflammasome et strat\u00e9gie des polypills dans le traitement du syndrome de Guillain-Barr\u00e9 \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2020-7\"><strong>Juillet 2020 (date de d\u00e9but ao\u00fbt 2020) <\/strong><\/a>\u00e0 Elsa Logarinho, Groupe Vieillissement et Aneuplo\u00efdie, IBMC \u2013 Instituto de Biologia Molecular e Celular, Porto, Portugal, <strong>\u00ab Am\u00e9lioration de la stabilit\u00e9 chromosomique par de petites mol\u00e9cules comme strat\u00e9gie s\u00e9noth\u00e9rapeutique pour le syndrome de Heidegger-Schmidt \u00bb <\/strong><\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2020-1\"><strong>Janvier 2020 (date de d\u00e9but f\u00e9vrier 2020) :<\/strong><\/a> au Dr Vicente Andr\u00e9s, PhD, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Espagne. \u00ab\u00a0G\u00e9n\u00e9ration de miniporcs transg\u00e9niques Lamin C-Stop (LCS) et CAG-Cre Yucatan pour \u00e9lever des miniporcs HGPS Yucatan pour des essais pr\u00e9cliniques\u00a0\u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2020-2\"><strong>Janvier 2020 (<b>date de d\u00e9but ao\u00fbt 2020<\/b>):<\/strong><\/a> au Dr Giovanna Lattanzi, PhD, Unit\u00e9 de l&#039;Institut de g\u00e9n\u00e9tique mol\u00e9culaire du CNR de Bologne, Italie. \u00ab Am\u00e9liorer la qualit\u00e9 de vie des personnes atteintes de prog\u00e9ria : un premier essai sur le mod\u00e8le murin LmnaG609G\/G609G \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2020-3\"><strong>Janvier 2020 (date de d\u00e9but f\u00e9vrier 2020) :<\/strong><\/a> au Dr Bum-Joon Park, PhD, Universit\u00e9 nationale de Pusan, R\u00e9publique de Cor\u00e9e. \u00ab Effet de la prog\u00e9rinine (SLC-D011) et du lonafarnib sur le HGPS : une \u00e9tude combin\u00e9e in vitro et in vivo \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2020-4\"><strong>Janvier 2020 (date de d\u00e9but janvier 2020) :<\/strong><\/a> \u00e0 David R. Liu, PhD, professeur Richard Merkin et directeur du Merkin Institute of Transformative Technologies in Healthcare, directeur du programme de biologie chimique et de sciences th\u00e9rapeutiques, membre principal de l&#039;Institut et vice-pr\u00e9sident de la facult\u00e9, Broad Institute, chercheur, Howard Hughes Medical Institute, professeur Thomas Dudley Cabot de sciences naturelles et professeur de chimie et de biologie chimique, Universit\u00e9 de Harvard. <strong>\u00ab Traitements d\u2019\u00e9dition de base pour HGPS \u00bb.<\/strong><\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2019-3\" target=\"_blank\" rel=\"noopener noreferrer\"><b>D\u00e9cembre 2019 (date de d\u00e9but d\u00e9cembre 2019) :<\/b><\/a> Au Dr Abigail Buchwalter, PhD, Universit\u00e9 de Californie \u00e0 San Francisco. \u00ab D\u00e9finition de la faisabilit\u00e9 de l\u2019\u00e9limination de la prog\u00e9rine comme traitement du syndrome de Heidegger-Schmidt \u00bb.<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2017-1\" target=\"_blank\" rel=\"noopener noreferrer\"><b>Octobre 2019 (date de d\u00e9but novembre 2019) :<\/b><\/a> Au Dr Colin Stewart, PhD, Institut de biologie m\u00e9dicale, Immunos, Singapour. \u00ab Briser le LINC pour supprimer la prog\u00e9ria. \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2017-1\" target=\"_blank\" rel=\"noopener noreferrer\"><b>Juin 2019 (date de d\u00e9but octobre 2019) :<\/b><\/a> Au Dr Martin Berg\u00f6, PhD, professeur, Karolinska Institutet, Huddinge. \u00abD\u00e9veloppement et tests pr\u00e9cliniques d&#039;inhibiteurs ICMT pour la th\u00e9rapie HGPS.\u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2017-1\" target=\"_blank\" rel=\"noopener noreferrer\"><b>Novembre 2017 (date de d\u00e9but novembre 2017) :<\/b><\/a> Au Dr Richard K. Assoian, PhD, professeur, Universit\u00e9 de Pennsylvanie, Philadelphie, PA. \u00ab Analyse et att\u00e9nuation de la rigidit\u00e9 art\u00e9rielle dans le syndrome de Heidegger-Schmidt : implications pour la dur\u00e9e de vie. \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2017-2\" target=\"_blank\" rel=\"noopener noreferrer\"><b>Septembre 2017 (date de d\u00e9but octobre 2017) :<\/b><\/a> Au Dr Toren Finkel, MD\/PhD, directeur de l&#039;Aging Institute, Pittsburgh, PA. \u00ab Autophagie vasculaire et progression du syndrome de Guillain-Barr\u00e9 \u00bb.<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2016-1\" target=\"_blank\" rel=\"noopener noreferrer\"><b>D\u00e9cembre 2016 (date de d\u00e9but 1er f\u00e9vrier 2017) :<\/b><\/a> \u00c0 Juan Carlos Belmonte Izpisua, Ph. D., professeur, Laboratoires d&#039;expression g\u00e9n\u00e9tique \u00e0 l&#039; <a title=\"Institut Salk d&#039;\u00e9tudes biologiques\" href=\"https:\/\/en.wikipedia.org\/wiki\/Salk_Institute_for_Biological_Studies\" target=\"_blank\" rel=\"noopener noreferrer\">Institut Salk d&#039;\u00e9tudes biologiques<\/a>, La Jolla, CA, USA. Il est l&#039;ancien directeur et a aid\u00e9 \u00e0 \u00e9tablir le <a title=\"es:Centro de Medicina Regenerativa de Barcelone\" href=\"https:\/\/es.wikipedia.org\/wiki\/Centro_de_Medicina_Regenerativa_de_Barcelona\" target=\"_blank\" rel=\"noopener noreferrer\">Centre de M\u00e9decine R\u00e9g\u00e9n\u00e9rative de Barcelone<\/a>Il est titulaire d&#039;un doctorat en biochimie et pharmacologie de l&#039;Universit\u00e9 de Bologne, en Italie, et de l&#039;Universit\u00e9 de Valence, en Espagne. Il est chercheur postdoctoral au Laboratoire europ\u00e9en de biologie mol\u00e9culaire (EMBL) de l&#039;Universit\u00e9 de Marbourg, \u00e0 Heidelberg, en Allemagne, et \u00e0 l&#039;UCLA, aux \u00c9tats-Unis. \u00ab Am\u00e9lioration des ph\u00e9notypes de vieillissement pr\u00e9matur\u00e9 dans le syndrome de Hutchinson-Gilford Progeria. \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2016-2\" target=\"_blank\" rel=\"noopener noreferrer\"><b>D\u00e9cembre 2016 (date de d\u00e9but 1er f\u00e9vrier 2017) :<\/b><\/a> \u00c0 Ricardo Villa-Bellosta, Ph. D., chef d\u2019\u00e9quipe, Institut de recherche en sant\u00e9 de l\u2019h\u00f4pital universitaire de la Fondation Jim\u00e9nez D\u00edaz (FIIS-FJD, Espagne). \u00ab Strat\u00e9gies th\u00e9rapeutiques pour r\u00e9tablir l\u2019hom\u00e9ostasie normale des pyrophosphates dans les HGPS. \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2016-3\" target=\"_blank\" rel=\"noopener noreferrer\"><b>D\u00e9cembre 2016 (date de d\u00e9but 1er f\u00e9vrier 2017) :<\/b><\/a> \u00c0 Isabella Saggio, PhD, professeure agr\u00e9g\u00e9e de g\u00e9n\u00e9tique et de th\u00e9rapie g\u00e9nique, Universit\u00e9 Sapienza (Rome, Italie). \u00ab La prot\u00e9ine t\u00e9lom\u00e9rique interagissant avec la lamine AKTIP dans le HGPS. \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2016-4\" target=\"_blank\" rel=\"noopener noreferrer\"><b>D\u00e9cembre 2016 (date de d\u00e9but 1er mars 2017) :<\/b><\/a> \u00c0 Tom Misteli, PhD, chercheur \u00e9m\u00e9rite du NIH et directeur du Centre de recherche sur le cancer du National Cancer Institute, NIH. \u00ab Tests in vivo de candidats traitements HGPS. \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2016-5\" target=\"_blank\" rel=\"noopener noreferrer\"><strong>Ao\u00fbt 2016 (date de d\u00e9but 1er janvier 2017) :<\/strong><\/a>\u00a0\u00c0 Silvia Ortega-Guti\u00e9rrez, Universidad Complutense de Madrid, Espagne : professeure associ\u00e9e depuis 2013 ; boursi\u00e8re Ram\u00f3n y Cajal, d\u00e9partement de chimie organique, 2008-2012 ; doctorat, 2004 ; a travaill\u00e9 sous la supervision de la professeure Mar\u00eda Luz L\u00f3pez-Rodr\u00edguez, d\u00e9partement de chimie m\u00e9dicinale, boursi\u00e8re Fulbright, laboratoire du professeur Ben Cravatt, biologie chimique et prot\u00e9omique, Institut de recherche Scripps en Californie, \u00c9tats-Unis ; \u00ab Nouveaux inhibiteurs de l&#039;isopr\u00e9nylcyst\u00e9ine carboxym\u00e9thyltransf\u00e9rase (ICMT) pour le traitement de la prog\u00e9ria.<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2016-6\" target=\"_blank\" rel=\"noopener noreferrer\"><strong>Juillet 2016 (date de d\u00e9but 1er octobre 2016) :<\/strong><\/a> \u00a0\u00c0 Roland Foisner, PhD, professeur de biochimie \u00e0 l&#039;universit\u00e9 m\u00e9dicale de Vienne et directeur adjoint des laboratoires Max F. Perutz, Vienne, Autriche. Coordinateur scientifique de l&#039;ancien projet de r\u00e9seau europ\u00e9en EURO-Laminopathies et r\u00e9dacteur en chef de la revue Nucleus ; \u00ab Contribution du dysfonctionnement des cellules endoth\u00e9liales aux maladies cardiovasculaires dans la prog\u00e9ria et implications pour les cibles diagnostiques et th\u00e9rapeutiques. \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2015-1\" target=\"_blank\" rel=\"noopener noreferrer\"><b>D\u00e9cembre 2015 (date de d\u00e9but 1er janvier 2016) :<\/b><\/a> \u00c0 Juan Carlos Belmonte Izpisua, PhD, professeur, Gene Expression Laboratories, The Salk Institute for Biological Studies, La Jolla, CA, USA. \u00ab L&#039;utilisation de nouvelles technologies pour identifier et valider des compos\u00e9s th\u00e9rapeutiques potentiels pour le traitement du syndrome de Hutchinson-Gilford-Progeria. \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2015-2\" target=\"_blank\" rel=\"noopener noreferrer\"><b>D\u00e9cembre 2015 (date de d\u00e9but 1er mars 2016) : <\/b><\/a><b>\u00a0<\/b>\u00c0 Jed William Fahey, Sc.D., directeur du Cullman Chemoprotection Center, <i>Professeur adjoint, <\/i>Universit\u00e9 Johns Hopkins, \u00c9cole de m\u00e9decine, D\u00e9partement de m\u00e9decine, Division de pharmacologie clinique, D\u00e9partement de pharmacologie et de sciences mol\u00e9culaires ; \u00c9cole de sant\u00e9 publique Bloomberg, D\u00e9partement de sant\u00e9 internationale, Centre de nutrition humaine ; \u00ab La capacit\u00e9 des isothiocyanates d&#039;origine v\u00e9g\u00e9tale \u00e0 surpasser l&#039;efficacit\u00e9 du sulforaphane, avec une toxicit\u00e9 r\u00e9duite pour les lign\u00e9es cellulaires de Progeria. \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2015-3\" target=\"_blank\" rel=\"noopener noreferrer\"><strong>Juin 2015 (date de d\u00e9but 1er juillet 2015) : <\/strong><\/a>\u00c0 Bum-Joon Park, Ph. D., pr\u00e9sident et professeur du d\u00e9partement de biologie mol\u00e9culaire, Universit\u00e9 nationale de Pusan, R\u00e9publique de Cor\u00e9e ; \u00ab Am\u00e9lioration de l&#039;effet th\u00e9rapeutique de JH4, inhibiteur de la liaison prog\u00e9rine-lamine A\/C, contre le syndrome de prog\u00e9ria. \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2015-4\" target=\"_blank\" rel=\"noopener noreferrer\"><strong>Juin 2015 (date de d\u00e9but 1er septembre 2015) : <\/strong><\/a>\u00c0 John P. Cooke, MD, PhD, Joseph C. \u00ab Rusty \u00bb Walter et Carole Walter Looke, titulaire de la chaire distingu\u00e9e pr\u00e9sidentielle de recherche sur les maladies cardiovasculaires, pr\u00e9sidente et membre \u00e0 part enti\u00e8re du d\u00e9partement des sciences cardiovasculaires du Houston Methodist Research Institute, directrice du Center for Cardiovascular Regeneration du Houston Methodist DeBakey Heart<b> <\/b>et le Centre vasculaire, Houston, TX ; \u00ab Th\u00e9rapie par t\u00e9lom\u00e9rase pour la prog\u00e9ria \u00bb.<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2015-5\" target=\"_blank\" rel=\"noopener noreferrer\"><strong>Juin 2015 (date de d\u00e9but 1er septembre 2015) : <\/strong><\/a>\u00c0 Francis Collins, MD, PhD, directeur des National Institutes of Health (NIH\/NHGRI), Bethesda, MD ; \u00ab Financement des candidats postdoctoraux pour la recherche HGPS. \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2015-6\" target=\"_blank\" rel=\"noopener noreferrer\"><strong>Juin 2015 (date de d\u00e9but 1er septembre 2015) : <\/strong><\/a>Dudley Lamming, PhD, professeur adjoint au d\u00e9partement de m\u00e9decine de l&#039;universit\u00e9 du Wisconsin-Madison, codirecteur de la plateforme de ph\u00e9notypage m\u00e9tabolique de la souris du d\u00e9partement de m\u00e9decine de l&#039;universit\u00e9 du Wisconsin-Madison, Madison, Wisconsin ; \u00ab Intervention dans la prog\u00e9ria par restriction d&#039;acides amin\u00e9s alimentaires sp\u00e9cifiques \u00bb.<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2015-7\" target=\"_blank\" rel=\"noopener noreferrer\"><strong>Juin 2015 (date de d\u00e9but 1er septembre 2015) :<\/strong>\u00a0<\/a>\u00c0 Cl\u00e1udia Cavadas, PhD, Centre de neurosciences et de biologie cellulaire (CNC), Universit\u00e9 de Coimbra, Coimbra Portugal ; \u00ab\u00a0Le NPY p\u00e9riph\u00e9rique inverse le ph\u00e9notype HGPS\u00a0: une \u00e9tude sur des fibroblastes humains et un mod\u00e8le de souris\u00a0\u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2014-1\" target=\"_blank\" rel=\"noopener noreferrer\"><strong><b>D\u00e9cembre 2014 (date de d\u00e9but 1er avril 2015) :\u00a0<\/b><\/strong><\/a>\u00c0 C\u00e9lia Alexandra Ferreira de Oliveira Aveleira, PhD, Centre de neurosciences et de biologie cellulaire (CNC) et Institut de recherche interdisciplinaire (IIIUC), Universit\u00e9 de Coimbra Portugal ; &quot;Ghr\u00e9line\u00a0: une nouvelle intervention th\u00e9rapeutique pour sauver le ph\u00e9notype du syndrome de Hutchinson\u2010Gilford Progeria&quot;<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2014-2\" target=\"_blank\" rel=\"noopener noreferrer\"><b>D\u00e9cembre 2014 (date de d\u00e9but 1er f\u00e9vrier 2015) :<\/b><\/a><b>\u00a0<\/b><\/strong>\u00c0 Jes\u00fas V\u00e1zquez Cobos, PhD, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Espagne ; \u00ab Quantification de la prog\u00e9rine farn\u00e9syl\u00e9e dans les tissus de souris prog\u00e9ro\u00efdes et les leucocytes circulants des patients atteints de prog\u00e9ria Hutchinson-Gilford \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2014-3\" target=\"_blank\" rel=\"noopener noreferrer\"><strong><b>D\u00e9cembre 2014 (date de d\u00e9but 1er f\u00e9vrier 2015) : <\/b><\/strong><\/a>\u00c0 Marsha Moses, PhD, Boston Children&#039;s Hospital, Boston, MA ; \u00ab D\u00e9couverte de nouveaux biomarqueurs non invasifs pour le syndrome de Hutchinson-Gilford prog\u00e9ria \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants_funded.html\/#JRabinowitz\" target=\"_blank\" rel=\"noopener noreferrer\"><strong><b>D\u00e9cembre 2014 (date de d\u00e9but 1er mars 2015) : <\/b><\/strong><\/a>\u00c0 Joseph Rabinowitz, PhD, Temple University School of Medicine, Philadelphie, PA ; \u00ab Co-administration m\u00e9di\u00e9e par un virus ad\u00e9no-associ\u00e9 de lamine A de type sauvage et de microARN contre la prog\u00e9rine \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2014-5\"><strong>Juillet 2014 (date de d\u00e9but 1er novembre 2014) :<\/strong><\/a> \u00c0 Vicente Andr\u00e9s Garc\u00eda, PhD, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Espagne ; \u00abG\u00e9n\u00e9ration d&#039;un mod\u00e8le porcin knock-in HGPS pour acc\u00e9l\u00e9rer le d\u00e9veloppement d&#039;applications cliniques efficaces\u00bb.<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2013-1\"><strong>Juin 2013 (date de d\u00e9but 1er septembre 2013) : <\/strong><\/a>Au Dr Brian Snyder, PhD, : Beth Israel Deaconess Medical Center, Boston, MA. ; \u00ab Caract\u00e9risation des ph\u00e9notypes musculo-squelettiques, craniofaciaux et cutan\u00e9s du mod\u00e8le murin de prog\u00e9ria G608G \u00bb.<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2013-2\"><strong>Juin 2013 (date de d\u00e9but 1er septembre 2013) : <\/strong><\/a>Au Dr Robert Goldman, PhD, : Northwestern University ; \u00ab Nouvelles perspectives sur le r\u00f4le de la prog\u00e9rine en pathologie cellulaire \u00bb.<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2013-3\"><strong>Juin 2013 (date de d\u00e9but 1er septembre 2013) : <\/strong><\/a>Au Dr Christopher Carroll, PhD, : Universit\u00e9 Yale, New Haven, CT ; \u00ab R\u00e9gulation de l&#039;abondance de la prog\u00e9rine par la prot\u00e9ine de la membrane nucl\u00e9aire interne Man1 \u00bb.<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2013-4\"><strong>Juin 2013 (date de d\u00e9but 1er septembre 2013) : <\/strong><\/a>Au Dr Katharine Ullman : Universit\u00e9 de l\u2019Utah, Salt Lake City, UT ; \u00ab \u00c9lucider l\u2019impact de la prog\u00e9rine sur le r\u00f4le de Nup153 dans la r\u00e9ponse aux dommages \u00e0 l\u2019ADN \u00bb.<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2013-5\"><strong>Juin 2013 (date de d\u00e9but 1er septembre 2013) : <\/strong><\/a>Au Dr Katherine Wilson : Johns Hopkins School of Medicine, Baltimore, MD ; \u00ab Expression naturelle de la prog\u00e9rine et cons\u00e9quences de la r\u00e9duction de l&#039;O-GlcNAcylation de la queue de la lamine A \u00bb.<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2013-6\"><strong>Juin 2013 (date de d\u00e9but 1er septembre 2013) :<\/strong><\/a> Au Dr Brian Kennedy, Buck Institute for Research on Aging, Novato, CA ; \u00ab Intervention contre le vieillissement par petites mol\u00e9cules dans la prog\u00e9ria \u00bb.<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2012-1\">D\u00e9cembre 2012 (date de d\u00e9but ao\u00fbt 2013) :<\/a> <\/strong>\u00a0Au Dr Gerardo Ferbeyre, Ph. D., Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Canada : \u00ab Contr\u00f4le de la clairance de la prog\u00e9rine par d\u00e9farn\u00e9sylation et phosphorylation de la s\u00e9rine 22 \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2012-2\"><strong>D\u00e9cembre 2012 (date de d\u00e9but f\u00e9vrier 2013) :<\/strong><\/a> Au Dr Thomas Misteli, PhD, National Cancer Institute NIH, Bethesda, MD : \u00ab D\u00e9couverte de petites mol\u00e9cules dans le HGPS \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2012-3\"><strong>D\u00e9cembre 2012 (date de d\u00e9but avril ou mai 2013) :<\/strong> <\/a>\u00c0 Karima Djabali, PhD, Universit\u00e9 technique de Munich, Munich, Allemagne : \u00ab Dynamique de la prog\u00e9rine au cours de la progression du cycle cellulaire \u00bb<strong><br \/><\/strong><\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2012-4\">Septembre 2012 :<\/a> <\/strong>\u00c0 Tom Misteli, Ph. D., National Cancer Institute, NIH, Bethesda, MD; Prix du technicien<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2012-5\">Juillet 2012 (date de d\u00e9but 1er septembre 2012) :<\/a> <\/strong>\u00c0 Vicente Andr\u00e9s Garc\u00eda, PhD, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Espagne ; &quot;Quantification de la prog\u00e9rine farn\u00e9syl\u00e9e et identification des g\u00e8nes qui activent les aberrants <em>LMNA<\/em> \u00e9pissage dans le syndrome de Hutchinson-Gilford Progeria\u201d<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2012-6\">Juillet 2012 (date de d\u00e9but 1er septembre 2012) :<\/a> <\/strong>Au Dr Samuel Benchimol, Universit\u00e9 York, Toronto, Canada : \u00ab Implication de p53 dans la s\u00e9nescence pr\u00e9matur\u00e9e du HGPS \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2012-7\"><strong>Juillet 2012 :<\/strong> <\/a>\u00c0 Tom Misteli, Ph. D., National Cancer Institute, NIH, Bethesda, MD ; Modification de la bourse de sp\u00e9cialit\u00e9<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2011-1\">D\u00e9cembre 2011 (date de d\u00e9but 1er mars 2012) :<\/a> <\/strong>Au Dr Thomas Dechat, PhD, Universit\u00e9 de m\u00e9decine de Vienne, Autriche ; \u00ab Association membranaire stable de la prog\u00e9rine et implications pour la signalisation pRb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2011-2\"><strong>D\u00e9cembre 2011 (date de d\u00e9but 1er mars 2012) : <\/strong><\/a>\u00c0 Maria Eriksson, Ph.D., Institut Karolinska, Su\u00e8de ; Analyse de la possibilit\u00e9 d&#039;inversion de la maladie de la prog\u00e9ria<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2011-3\">D\u00e9cembre 2011 (date de d\u00e9but 1er mars 2012) :<\/a> <\/strong>\u00c0 Colin L. Stewart D.Phil, Institut de biologie m\u00e9dicale, Singapour ; \u00ab D\u00e9finition de la base mol\u00e9culaire de la d\u00e9t\u00e9rioration du muscle lisse vasculaire dans la prog\u00e9ria<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2011-4\"><strong>Septembre 2011 (date de d\u00e9but 1er janvier 2012) :<\/strong><\/a> Au Dr Dylan Taatjes, Universit\u00e9 du Colorado, Boulder, CO : Profil m\u00e9tabolique comparatif des cellules HGPS et \u00e9valuation des changements ph\u00e9notypiques lors de la modulation des m\u00e9tabolites cl\u00e9s<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2011-5\"><strong>Juin 2011 (date de d\u00e9but 1er janvier 2012) :<\/strong><\/a> \u00e0 Jan Lammerding, PhD, Institut Weill de biologie cellulaire et mol\u00e9culaire de l&#039;Universit\u00e9 Cornell, Ithaca, NY ; Dysfonctionnement des cellules musculaires lisses vasculaires dans le syndrome de Hutchinson-Gilford-Progeria<strong>\u00a0<\/strong><\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2010-1\">D\u00e9cembre 2010 (date de d\u00e9but 1er avril 2011) :<\/a> <\/strong>\u00c0 Robert D. Goldman, PhD, Northwestern University Medical School, Chicago, IL ; Un r\u00f4le pour les lamines de type B dans la prog\u00e9ria<strong>\u00a0<\/strong><\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2010-2\">D\u00e9cembre 2010 :<\/a> <\/strong>\u00c0 John Graziotto, PhD, Massachusetts General Hospital, Boston, MA ; \u00c9limination de la prot\u00e9ine prog\u00e9rine comme cible th\u00e9rapeutique dans le syndrome de Hutchinson-Gilford de la prog\u00e9ria<strong><br \/><\/strong><\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2010-3\"><strong>D\u00e9cembre 2010 (Date de d\u00e9but 1er avril 2011) :<\/strong><\/a> \u00c0 Tom Glover, PhD, U Michigan, Ann Arbor, MI ; \u00ab Identification des g\u00e8nes responsables de la prog\u00e9ria et du vieillissement pr\u00e9matur\u00e9 par s\u00e9quen\u00e7age de l&#039;exome \u00bb<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2010-4\">D\u00e9cembre 2010 (date de d\u00e9but 1er mars 2011) :<\/a> <\/strong>\u00c0 Yue Zou, PhD, East Tennessee State University, Johnson City, TN ; M\u00e9canismes mol\u00e9culaires de l&#039;instabilit\u00e9 du g\u00e9nome dans le HGPS<strong>\u00a0<\/strong><\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2010-5\">D\u00e9cembre 2010 (date de d\u00e9but 1er janvier 2011) :<\/a> <\/strong>\u00c0 Kan Cao, PhD, Universit\u00e9 du Maryland, College Park, MD ; La rapamycine inverse le ph\u00e9notype cellulaire et am\u00e9liore la clairance des prot\u00e9ines mutantes dans le syndrome de Hutchinson Gilford Progeria<strong>\u00a0<\/strong><\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2010-6\">Juin 2010 (date de d\u00e9but 1er octobre 2010) :<\/a> <\/strong>\u00c0 Evgeny Makarov, PhD, Universit\u00e9 Brunel, Uxbridge, Royaume-Uni ; Identification des r\u00e9gulateurs d&#039;\u00e9pissage LMNA par prot\u00e9omique comparative des complexes spliceosomal.<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2009-1\">Octobre 2009 :<\/a><\/strong>\u00a0 \u00e0 Jason D. Lieb, PhD, Universit\u00e9 de Caroline du Nord, Chapel Hill NC ; Interactions entre les g\u00e8nes et la lamine A\/prog\u00e9rine : une fen\u00eatre sur la compr\u00e9hension de la pathologie et du traitement de la prog\u00e9ria<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2009-2\">Octobre 2009 :<\/a><\/strong> \u00c0 Tom Misteli, PhD, National Cancer Institute, NIH, Bethesda, MD ; Identification de petites mol\u00e9cules modulatrices de l&#039;\u00e9pissage LMNA<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2009-3\">Ao\u00fbt 2009 :<\/a><\/strong> \u00e0 William L. Stanford, Ph. D., Universit\u00e9 de Toronto, Canada<br \/>Cellules souches pluripotentes induites (iPSC) issues de fibroblastes de patients atteints de HGPS pour \u00e9lucider le m\u00e9canisme mol\u00e9culaire associ\u00e9 \u00e0 la diminution de la fonction vasculaire<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2009-4\">Juillet 2009 :<\/a><\/strong> \u00e0 Jakub Tolar, Universit\u00e9 du Minnesota, Minneapolis, MN ;<br \/>Correction des cellules pluripotentes induites par la prog\u00e9ria humaine par recombinaison homologue<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2008-1\">Septembre 2008 (date de d\u00e9but janvier 2009) :<\/a><\/strong> \u00c0 Kris Noel Dahl, PhD, Universit\u00e9 Carnegie Mellon, Pittsburgh, PA\u00a0;<br \/>\u00ab Quantification du recrutement de la prog\u00e9rine dans les membranes \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2007-1\"><strong>Octobre 2007<\/strong>:<\/a> \u00c0 Michael A. Gimbrone, Jr., MD, Brigham and Women&#039;s Hospital et Harvard Medical School, Boston, MA Dysfonctionnement endoth\u00e9lial et pathobiologie de l&#039;ath\u00e9roscl\u00e9rose acc\u00e9l\u00e9r\u00e9e dans le syndrome de Hutchinson-Gilford-Progeria<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2007-2\"><strong>Septembre 2007 (Date de d\u00e9but janvier 2008) :<\/strong><\/a> \u00c0 Bryce M. Paschal, PhD, Facult\u00e9 de m\u00e9decine de l&#039;Universit\u00e9 de Virginie, Charlottesville, Virginie ; Transport nucl\u00e9aire dans le syndrome de prog\u00e9ria de Hutchinson-Guilford<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2007-3\">Mai 2007 :<\/a><\/strong> \u00c0 Thomas N. Wight, PhD, Benaroya Research Institute, Seattle, WA ; L&#039;utilisation d&#039;un mod\u00e8le murin de HGPS pour d\u00e9finir l&#039;influence de l&#039;expression de Lamin AD50 sur la production de matrice extracellulaire vasculaire et le d\u00e9veloppement de maladies vasculaires.<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2007-4\">Mars 2007 :<\/a><\/strong> \u00c0 Jemima Barrowman, PhD, Johns Hopkins School of Medicine, Baltimore, MD ; M\u00e9canisme fondamental du traitement de la lamine A : pertinence pour le trouble du vieillissement HGPS<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2006-1\">Ao\u00fbt 2006 :<\/a><\/strong> \u00c0 Zhongjun Zhou, PhD, Universit\u00e9 de Hong Kong, Chine. Th\u00e9rapie par cellules souches pour le vieillissement pr\u00e9matur\u00e9 li\u00e9 \u00e0 la laminopathie<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2006-2\">Ao\u00fbt 2006 :<\/a><\/strong> \u00c0 Michael Sinensky, PhD, Universit\u00e9 d&#039;\u00c9tat de l&#039;Est du Tennessee, Johnson City, TN\u00a0;<br \/>Effet des FTI sur la structure et l&#039;activit\u00e9 de la prog\u00e9rine<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2006-3\">Juin 2006 :<\/a><\/strong> \u00c0 Jan Lammerding, PhD, Brigham and Women&#039;s Hospital, Cambridge, MA ; Le r\u00f4le de la m\u00e9canique nucl\u00e9aire et de la m\u00e9canotransduction dans le syndrome de Hutchinson-Gilford Progeria et l&#039;effet du traitement par inhibiteur de la farn\u00e9syltransf\u00e9rase<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2006-4\">Juin 2006 :<\/a><\/strong>\u00c0 Tom Misteli, Ph. D., National Cancer Institute, NIH, Bethesda, MD\u00a0;<br \/>Approches th\u00e9rapeutiques mol\u00e9culaires pour le syndrome de Heidegger par correction de l&#039;\u00e9pissage du pr\u00e9-ARNm<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2005-1\">Juin 2005 :<\/a> <\/strong>\u00c0 Lucio Comai, PhD, Universit\u00e9 de Californie du Sud, Los Angeles, CA ; Analyse fonctionnelle du syndrome de Hutchinson-Gilford de la prog\u00e9ria<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2005-2\">Juin 2005 :<\/a> <\/strong>\u00c0 Loren G. Fong, PhD, Universit\u00e9 de Californie, Los Angeles, CA\u00a0;<br \/>De nouveaux mod\u00e8les de souris pour \u00e9tudier la cause du syndrome de Hutchinson-Gilford<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2005-3\">Janvier 2005 : <\/a><\/strong>Au Dr Karima Djabali, PhD, Universit\u00e9 de Columbia, New York, NY ; D\u00e9finition des effets n\u00e9gatifs dominants de la prog\u00e9rine sur les fonctions nucl\u00e9aires dans les cellules HGPS<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2004-1\">D\u00e9cembre 2004 : <\/a><\/strong>\u00c0 Robert D. Goldman, PhD et Dale Shumaker, PhD, \u00c9cole de m\u00e9decine de l&#039;Universit\u00e9 Northwestern, Chicago, Illinois<br \/>Les effets de la mutation majeure sur la fonction de la lamine A humaine dans la r\u00e9plication de l&#039;ADN<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2004-2\"><strong>Ao\u00fbt 2004 (Date de d\u00e9but janvier 2005) : <\/strong><\/a>\u00c0 Stephen Young, PhD, UCLA, Los Angeles, CA ; pour son projet intitul\u00e9 \u00ab Exp\u00e9riences g\u00e9n\u00e9tiques sur des souris pour comprendre la prog\u00e9ria \u00bb.<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2004-3\"><strong>Avril 2004 :<\/strong><\/a> \u00c0 Monica Mallampalli, Ph. D., et Susan Michaelis, Ph. D., \u00c9cole de m\u00e9decine Johns Hopkins, Baltimore, MD ; \u00ab Structure, localisation et analyse ph\u00e9notypique de la prog\u00e9rine, la forme mutante de la pr\u00e9lamine A dans le HGPS \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2003-1\"><strong>D\u00e9cembre 2003 :<\/strong><\/a> \u00c0 Joan Lemire, Ph. D., Tufts University School of Medicine, Boston, MA ; \u00ab D\u00e9veloppement d\u2019un mod\u00e8le de cellules musculaires lisses pour l\u2019\u00e9tude du syndrome de Hutchinson-Gilford Progeria : l\u2019aggr\u00e9cane est-il un \u00e9l\u00e9ment important du ph\u00e9notype ? \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2003-2\"><strong>D\u00e9cembre 2003 :<\/strong><\/a> \u00c0 W. Ted Brown, MD, PhD, FACMG, Institut de recherche fondamentale sur les troubles du d\u00e9veloppement, Staten Island, NY : \u00ab Effets de mutation n\u00e9gatifs dominants de la prog\u00e9rine \u00bb<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2003-3\">Septembre 2003 :<\/a><\/strong> \u00c0 Thomas W. Glover, Ph.D., Universit\u00e9 du Michigan, \u00ab<br \/>R\u00f4le des mutations de la lamine A dans le syndrome de Hutchinson-Gilford progeria<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2002-1\">Mai 2002 :<\/a><\/strong>\u00a0Au professeur associ\u00e9 Anthony Weiss de l&#039;Universit\u00e9 de Sydney, Australie, Titre du projet : Marqueurs mol\u00e9culaires candidats pour le syndrome de Hutchinson-Gilford-Progeria<\/li>\n<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2001-1\">Janvier 2001 (Date de d\u00e9but juillet 2001) :<\/a><\/strong> \u00c0 John M. Sedivy, PhD, Brown University, Providence, RI ; et Junko Oshima, MD, PhD, University of Washington, Seattle, WA, \u00ab Clonage du g\u00e8ne du syndrome de Hutchinson-Gilford Progeria par compl\u00e9mentation de cellules somatiques \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2001-2\"><strong>D\u00e9cembre 2001 (<\/strong><strong>Date de d\u00e9but<\/strong><strong> f\u00e9vrier 2002) :<\/strong><\/a> \u00c0 Thomas W. Glover, Ph.D., Universit\u00e9 du Michigan, \u00ab Maintenance du g\u00e9nome dans le syndrome de Hutchinson-Gilford-Progeria \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#2000-1\"><strong>Janvier 2000 :<\/strong><\/a>\u00a0\u00c0 Leslie B. Gordon, MD, PhD, Tufts University School of Medicine, Boston, MA ; \u00ab Le r\u00f4le de l&#039;acide hyaluronique dans le syndrome de Hutchinson-Gilford prog\u00e9ria \u00bb<\/li>\n<li><a href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/#1999-1\"><strong>Ao\u00fbt 1999 :<\/strong><\/a> \u00c0 Leslie B. Gordon, MD, PhD, Tufts University School of Medicine, Boston, MA ; \u00ab La physiopathologie de l&#039;art\u00e9rioscl\u00e9rose est li\u00e9e au syndrome de Hutchinson-Gilford-Progeria \u00bb<\/li>\n<\/ul>\n<p>[\/et_pb_text][et_pb_text admin_label=\u201d2023-RVB\u201d module_id=\u201d2023-RVB\u201d _builder_version=\u201d4.19.5\u2033 global_colors_info=\u201d{}\u201d]<\/p>\n<p style=\"font-weight: 400;\"><strong>Mars 2023 :<\/strong> \u00e0 Ricardo Villa-Bellosta, Saint-Jacques-de-Compostelle, Espagne. \u00ab Progeria et calcification vasculaire : r\u00e9gime et traitements. \u00bb<\/p>\n<p style=\"font-weight: 400;\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2023\/02\/RVilla-225x300.png\" width=\"147\" height=\"196\" alt=\"\" class=\"wp-image-16446 alignright size-medium\" srcset=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2023\/02\/RVilla-225x300.png 225w, https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2023\/02\/RVilla.png 265w\" sizes=\"(max-width: 147px) 100vw, 147px\" \/>Un domaine cl\u00e9 de recherche dans le laboratoire du Dr Villa-Bellosta est la calcification excessive du syst\u00e8me cardiovasculaire, y compris l&#039;aorte, l&#039;art\u00e8re coronaire et les valves aortiques, qui d\u00e9termine en grande partie la mortalit\u00e9 pr\u00e9coce chez les enfants atteints de HGPS. Le m\u00e9canisme mol\u00e9culaire de la calcification vasculaire dans le HGPS a d\u00e9j\u00e0 \u00e9t\u00e9 analys\u00e9 chez des souris knock-in LmnaG609G\/+, qui pr\u00e9sentent une d\u00e9ficience profonde en pyrophosphate extracellulaire, un inhibiteur endog\u00e8ne cl\u00e9 de la calcification. Dans ce projet, nous cherchons \u00e0 d\u00e9terminer les m\u00e9canismes mol\u00e9culaires qui favorisent ou r\u00e9duisent la calcification vasculaire et la long\u00e9vit\u00e9 dans le HGPS, en nous concentrant sur l&#039;importance de nutriments sp\u00e9cifiques consomm\u00e9s quotidiennement. De plus, nous pr\u00e9voyons d&#039;analyser l&#039;efficacit\u00e9 de deux nouvelles approches th\u00e9rapeutiques potentielles (qui r\u00e9tablissent l&#039;hom\u00e9ostasie du pyrophosphate) qui pourraient am\u00e9liorer la qualit\u00e9 de vie et la long\u00e9vit\u00e9 des souris et des enfants atteints de HGPS. Nous pr\u00e9voyons d&#039;utiliser des souris knock-in LmnaG609G\/+ et des cellules musculaires lisses vasculaires de l&#039;aorte pour analyser l&#039;effet de ces nutriments\/traitements sur la calcification vasculaire et la long\u00e9vit\u00e9 in vivo, seuls et associ\u00e9s au FTI-lonafarnib.<\/p>\n<p>[\/et_pb_text][et_pb_text admin_label=\u201d2022-1KD\u201d module_id=\u201d2022-SOG\u201d _builder_version=\u201d4.18.1\u2033 global_colors_info=\u201d{}\u201d]<\/p>\n<p style=\"text-align: left;\">\n<p style=\"font-weight: 400;\"><strong>Novembre 2022 : <\/strong>\u00e0 Silvia Ortega Gutierrez, Universit\u00e9 Complutense, Madrid Espagne<img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2022\/12\/S-Ortega-Picture-e1670424989123-150x150.jpg\" width=\"150\" height=\"150\" alt=\"\" class=\"wp-image-16080 alignright size-thumbnail\" \/><br \/>\u00ab La r\u00e9duction des niveaux de prog\u00e9rine par de petites mol\u00e9cules comme nouvelle approche pour le traitement de la prog\u00e9ria \u00bb<\/p>\n<p style=\"font-weight: 400;\">Des donn\u00e9es r\u00e9centes sugg\u00e8rent que le facteur le plus important dans l&#039;issue fatale du syndrome de prog\u00e9ria de Hutchinson-Gilford (HGPS ou prog\u00e9ria) est l&#039;accumulation de prog\u00e9rine, la forme mut\u00e9e de la lamine A qui cause la prog\u00e9ria. Les approches g\u00e9n\u00e9tiques visant \u00e0 diminuer les niveaux de prog\u00e9rine soit en interagissant avec son ARN soit en effectuant une correction g\u00e9nique induisent des am\u00e9liorations significatives du ph\u00e9notype de la maladie. Dans ce projet, nous aborderons la r\u00e9duction directe de la prog\u00e9rine par la conception et la synth\u00e8se de petites mol\u00e9cules appel\u00e9es chim\u00e8res ciblant la prot\u00e9olyse (PROTAC). Cette classe de compos\u00e9s, d\u00e9velopp\u00e9e pour d&#039;autres maladies principalement au cours de la derni\u00e8re d\u00e9cennie, est capable de se lier sp\u00e9cifiquement \u00e0 une prot\u00e9ine et de la marquer pour la d\u00e9gradation prot\u00e9osomale, r\u00e9duisant ainsi ses niveaux. \u00c0 partir d&#039;un hit pr\u00e9c\u00e9demment identifi\u00e9 dans notre laboratoire, nous r\u00e9aliserons un programme de chimie m\u00e9dicinale visant \u00e0 obtenir des compos\u00e9s am\u00e9lior\u00e9s en termes d&#039;activit\u00e9 biologique et de param\u00e8tres pharmacocin\u00e9tiques. Le ou les compos\u00e9s optimaux seront \u00e9valu\u00e9s pour leur efficacit\u00e9 dans un mod\u00e8le in vivo de prog\u00e9ria.<\/p>\n<p style=\"font-weight: 400;\">[\/et_pb_text][et_pb_text admin_label=\u201d2022-1KD\u201d module_id=\u201d2022-LA\u201d _builder_version=\u201d4.18.1\u2033 global_colors_info=\u201d{}\u201d]<\/p>\n<p style=\"font-weight: 400;\"><strong><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2022\/12\/L.Arbibepicture-150x150.jpg\" width=\"150\" height=\"150\" alt=\"\" class=\"wp-image-16079 alignright size-thumbnail\" srcset=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2022\/12\/L.Arbibepicture-150x150.jpg 150w, https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2022\/12\/L.Arbibepicture-300x300.jpg 300w, https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2022\/12\/L.Arbibepicture.jpg 358w\" sizes=\"(max-width: 150px) 100vw, 150px\" \/>Octobre 2022 :<\/strong> \u00e0 Laurence Arbibe, Institut Necker-Enfants Malades (INEM), Paris, France<br \/>\u00ab D\u00e9crypter le vieillissement intestinal acc\u00e9l\u00e9r\u00e9 dans la physiopathologie du syndrome de Guillain-Barr\u00e9 : une approche int\u00e9grative \u00bb<\/p>\n<p style=\"font-weight: 400;\"><span>Le laboratoire du Dr Arbibe a r\u00e9cemment montr\u00e9 que l&#039;inflammation chronique modifie consid\u00e9rablement<\/span><span>contr\u00f4le de la qualit\u00e9 de l&#039;\u00e9pissage du pr\u00e9-ARNm dans l&#039;intestin, l&#039;une des cons\u00e9quences \u00e9tant la production de la prot\u00e9ine prog\u00e9rine. Dans le cadre du pr\u00e9sent projet, elle explorera l&#039;impact de la toxicit\u00e9 de la prog\u00e9rine sur l&#039;\u00e9pith\u00e9lium intestinal,<\/span><span> <\/span><span>suivi des effets sur le renouvellement des cellules souches et l&#039;int\u00e9grit\u00e9 de la barri\u00e8re muqueuse. Elle visera \u00e9galement \u00e0 identifier les signaux environnementaux pro-vieillissement affectant l&#039;\u00e9pissage de l&#039;ARN dans le HGPS en mettant en \u0153uvre un mod\u00e8le de souris rapporteur permettant <i>in vivo<\/i> suivi de l&#039;\u00e9v\u00e9nement d&#039;\u00e9pissage sp\u00e9cifique de la prog\u00e9rine<i>.<\/i> Dans l\u2019ensemble, ce projet abordera les cons\u00e9quences de la maladie prog\u00e9ria sur l\u2019int\u00e9grit\u00e9 de l\u2019intestin, tout en fournissant \u00e0 la communaut\u00e9 scientifique de nouvelles ressources pour \u00e9tudier les facteurs sp\u00e9cifiques aux tissus et aux cellules du vieillissement acc\u00e9l\u00e9r\u00e9 dans le HGPS.<\/span><\/p>\n<p style=\"font-weight: 400;\">[\/et_pb_text][et_pb_text admin_label=\u201d2022-1KD\u201d module_id=\u201d2022-1KD\u201d _builder_version=\u201d4.16\u2033 global_colors_info=\u201d{}\u201d]<\/p>\n<p style=\"text-align: left;\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-14651 size-full alignright\" src=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2022\/03\/Karima-Djabali.jpeg\" alt=\"\" width=\"115\" height=\"169\" \/><\/p>\n<p style=\"font-weight: 400;\"><strong>Janvier 2022 :<\/strong>\u00a0au Dr Karima Djabali, PhD, Universit\u00e9 technique de Munich, Munich, Allemagne : \u00ab Traitement du syndrome de Hutchinson-Gilford-Progeria avec deux m\u00e9dicaments approuv\u00e9s par la FDA combin\u00e9s \u2014\u00a0<em>Lonafarnib<\/em>\u00a0et\u00a0<em>Baricitinib<\/em>, des inhibiteurs sp\u00e9cifiques de la farn\u00e9syltransf\u00e9rase et de la kinase JAK1\/2 respectivement. \u00bb<\/p>\n<p style=\"font-weight: 400;\">Le projet du Dr Djabali permettra de tester sur un mod\u00e8le murin de HGPS si le traitement avec la combinaison de\u00a0<em>Lonafarnib<\/em>\u00a0et\u00a0<em>Baricitinib,<\/em>\u00a0Un m\u00e9dicament anti-inflammatoire retardera le d\u00e9veloppement des pathologies typiques du HGPS, \u00e0 savoir les maladies vasculaires, l&#039;atrophie cutan\u00e9e, l&#039;alop\u00e9cie et la lipodystrophie. Ses d\u00e9couvertes pr\u00e9c\u00e9dentes lient la voie JAK-STAT aux caract\u00e9ristiques de l&#039;inflammation et des maladies cellulaires du HGPS. L&#039;exposition cellulaire du HGPS au baricitinib a am\u00e9lior\u00e9 la croissance cellulaire et la fonction mitochondriale, r\u00e9duit les facteurs pro-inflammatoires, r\u00e9duit les taux de prog\u00e9rine et am\u00e9lior\u00e9 l&#039;adipogen\u00e8se. De plus, l&#039;administration de baricitinib avec le lonafarnib a am\u00e9lior\u00e9 certains ph\u00e9notypes cellulaires par rapport au lonafarnib seul.<\/p>\n<p style=\"font-weight: 400;\">[\/et_pb_text][et_pb_text admin_label=\u201d2021-7\u2033 module_id=\u201d2021-7\u2033 _builder_version=\u201d4.16\u2033 global_colors_info=\u201d{}\u201d]<\/p>\n<p style=\"text-align: left;\"><strong><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2021\/07\/Lanzuolo-Photo-150x150.png\" width=\"150\" height=\"150\" alt=\"\" class=\"wp-image-13256 alignright size-thumbnail\" \/><\/strong><\/p>\n<p><strong>Juillet 2021 :<\/strong>\u00a0\u00e0 Chiara Lanzuolo, Instituto Nazionale Genetica Molecolare, Milan, Italie.<br \/>\u00ab Suivi de la r\u00e9cup\u00e9ration de la structure et de la fonction du g\u00e9nome suite \u00e0 des traitements pharmacologiques dans le syndrome de Hutchinson Gilford Progeria \u00bb<strong>\u00a0<\/strong><\/p>\n<p>Le Dr Lanzuolo est une experte dans le domaine de la structure 3D de l&#039;ADN. Son groupe a r\u00e9cemment rapport\u00e9 que la structure tridimensionnelle sp\u00e9cifique \u00e0 la cellule du g\u00e9nome est maintenue par l&#039;assemblage correct de la lame nucl\u00e9aire et est rapidement perdue dans la pathogen\u00e8se de la prog\u00e9ria. Dans ce projet, elle utilisera des technologies de pointe sur un mod\u00e8le de souris prog\u00e9rique pour aborder sp\u00e9cifiquement les m\u00e9canismes mol\u00e9culaires qui se produisent pendant les premi\u00e8res phases de la maladie et qui permettent ou acc\u00e9l\u00e8rent l&#039;apparition de la pathologie. De plus, elle analysera la r\u00e9cup\u00e9ration fonctionnelle du g\u00e9nome apr\u00e8s des traitements pharmacologiques.<strong><\/strong><\/p>\n<p>&nbsp;<\/p>\n<p>[\/et_pb_text][et_pb_text admin_label=\u201d2021-7MC\u201d module_id=\u201d2021-7MC\u201d _builder_version=\u201d4.16\u2033 global_colors_info=\u201d{}\u201d]<\/p>\n<p><strong><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2021\/07\/CorderoPhoto-150x150.png\" width=\"150\" height=\"150\" alt=\"\" class=\"wp-image-13257 alignright size-thumbnail\" \/>Juillet 2021 :<\/strong> \u00e0 Mario Cordero, Institut de recherche et d&#039;innovation biom\u00e9dicale de Cadix (INIBICA), Cadix, Espagne.<br \/>\u00ab Inhibition de l&#039;inflammasome et strat\u00e9gie des polypills dans le traitement du HGPS \u00bb<\/p>\n<p>Le projet du Dr Cordero explorera les implications mol\u00e9culaires du complexe NLRP3-inflammasome dans la physiopathologie de la Progeria et \u00e9tudiera les effets d&#039;un inhibiteur sp\u00e9cifique de NLRP3-inflammasome avec le lonafarnib. Ses pr\u00e9c\u00e9dentes d\u00e9couvertes montrent un r\u00f4le possible du NLRP3 et un effet potentiel de son inhibition sur la survie d&#039;un mod\u00e8le murin de Progeria. Il va maintenant comparer un traitement m\u00e9dicamenteux unique \u00e0 base de lonafarnib avec un inhibiteur sp\u00e9cifique de NLRP3 et un traitement combin\u00e9 des deux pour d\u00e9terminer lequel est le plus efficace. Les r\u00e9sultats de ce projet contribueront, esp\u00e9rons-le, \u00e0 acc\u00e9l\u00e9rer un essai clinique sur la Progeria utilisant deux compos\u00e9s test\u00e9s dans des essais de phase 2a sur l&#039;homme avec un bon effet et une bonne tol\u00e9rance.<\/p>\n<p>[\/et_pb_text][et_pb_text admin_label=\u201d2020-7\u2033 module_id=\u201d2020-7\u2033 _builder_version=\u201d4.16\u2033 global_colors_info=\u201d{}\u201d]<\/p>\n<p style=\"text-align: left;\"><strong><\/strong><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2020\/09\/Logarinho-150x150.jpg\" width=\"150\" height=\"150\" alt=\"\" class=\"wp-image-11072 aligncenter size-thumbnail\" style=\"float: right;\" \/><\/p>\n<p style=\"text-align: left;\"><strong>Juillet 2020 :<\/strong>\u00a0(date de d\u00e9but ao\u00fbt 2020) \u00e0 Elsa Logarinho, Aging and Aneuplo\u00efdy Group, IBMC \u2013 Instituto de Biologia Molecular e Celular, Porto, Portugal, <strong>\u00ab Am\u00e9lioration de la stabilit\u00e9 chromosomique par de petites mol\u00e9cules comme strat\u00e9gie s\u00e9noth\u00e9rapeutique pour le syndrome de Heidegger-Schmidt \u00bb <\/strong><\/p>\n<p>Le projet du Dr Logarinho vise \u00e0 explorer les effets d&#039;un agoniste \u00e0 petite mol\u00e9cule de la kin\u00e9sine 13 d\u00e9polym\u00e9risante des microtubules (MT) Kif2C\/MCAK (UMK57), pour contrer les caract\u00e9ristiques cellulaires et physiologiques du HGPS. Ses pr\u00e9c\u00e9dentes d\u00e9couvertes classent Kif2C comme un acteur cl\u00e9 de l&#039;instabilit\u00e9 g\u00e9nomique et chromosomique, qui sont li\u00e9es de mani\u00e8re causale et sont \u00e9galement \u00e9tablies comme les principales causes des syndromes prog\u00e9ro\u00efdes. La stabilisation des chromosomes de la Progeria au niveau cellulaire vise \u00e0 am\u00e9liorer la maladie dans tout le corps.<\/p>\n<p><strong>\u00a0<\/strong><\/p>\n<p>[\/et_pb_text][et_pb_text admin_label=\u201d2020-1\u2033 module_id=\u201d2020-1\u2033 _builder_version=\u201d4.16\u2033 global_colors_info=\u201d{}\u201d]<\/p>\n<p style=\"text-align: left;\"><strong><img loading=\"lazy\" decoding=\"async\" class=\"alignright wp-image-9344\" src=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2020\/01\/Andres.jpg\" alt=\"\" width=\"144\" height=\"144\" srcset=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2020\/01\/Andres.jpg 200w, https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2020\/01\/Andres-150x150.jpg 150w\" sizes=\"(max-width: 144px) 100vw, 144px\" \/>Janvier 2020 :<\/strong> au Dr Vicente Andr\u00e9s, PhD, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Espagne. \u00ab\u00a0G\u00e9n\u00e9ration de miniporcs transg\u00e9niques Lamin C-Stop (LCS) et CAG-Cre Yucatan pour \u00e9lever des miniporcs HGPS Yucatan pour des essais pr\u00e9cliniques\u00a0\u00bb<\/p>\n<p>L&#039;un des principaux domaines de recherche du laboratoire du Dr Andr\u00e9s est la cr\u00e9ation de nouveaux mod\u00e8les animaux de la prog\u00e9ria. Les grands mod\u00e8les animaux reproduisent les principales caract\u00e9ristiques de la maladie humaine bien mieux que les mod\u00e8les murins, ce qui nous permet d&#039;\u00e9tudier les maladies cardiovasculaires et de tester des th\u00e9rapies. Le mod\u00e8le du Dr Andr\u00e9s am\u00e9liorera un nouveau mod\u00e8le de miniporc de la prog\u00e9ria qui \u00e9tait auparavant financ\u00e9 par le PRF.\u00a0<\/p>\n<p><strong>\u00a0<\/strong><\/p>\n<p>[\/et_pb_text][et_pb_text admin_label=\u201d2020-2\u2033 module_id=\u201d2020-2\u2033 _builder_version=\u201d4.16\u2033 custom_padding=\u201d||51px|||\u201d global_colors_info=\u201d{}\u201d]<\/p>\n<p style=\"text-align: left;\"><strong><img loading=\"lazy\" decoding=\"async\" class=\"alignright wp-image-9351\" src=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2020\/01\/Lattanzi-200x200-1.jpg\" alt=\"\" width=\"144\" height=\"144\" srcset=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2020\/01\/Lattanzi-200x200-1.jpg 200w, https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2020\/01\/Lattanzi-200x200-1-150x150.jpg 150w\" sizes=\"(max-width: 144px) 100vw, 144px\" \/>Janvier 2020 :<\/strong> au Dr Giovanna Lattanzi, PhD, Unit\u00e9 de l&#039;Institut de g\u00e9n\u00e9tique mol\u00e9culaire du CNR de Bologne, Italie. \u00ab Am\u00e9liorer la qualit\u00e9 de vie des personnes atteintes de prog\u00e9ria : un premier essai sur le mod\u00e8le murin LmnaG609G\/G609G \u00bb<\/p>\n<p>Le Dr Lattanzi abordera la question de la qualit\u00e9 de vie des patients atteints de prog\u00e9ria, une maladie li\u00e9e \u00e0 un \u00e9tat inflammatoire chronique. La normalisation de l\u2019\u00e9tat inflammatoire peut aider les patients \u00e0 faire face aux traitements pharmacologiques ; si leur \u00e9tat de sant\u00e9 s\u2019am\u00e9liore, ils peuvent atteindre une meilleure efficacit\u00e9 et prolonger leur dur\u00e9e de vie. Le Dr Lattanzi testera des strat\u00e9gies de r\u00e9duction de l\u2019inflammation chronique dans un mod\u00e8le murin de prog\u00e9ria, dans le but de transf\u00e9rer les r\u00e9sultats aux patients.<\/p>\n<p>[\/et_pb_text][et_pb_text admin_label=\u201d2020-3\u2033 module_id=\u201d2020-3\u2033 _builder_version=\u201d4.16\u2033 min_height=\u201d244px\u201d custom_margin=\u201d||-51px|||\u201d global_colors_info=\u201d{}\u201d]<\/p>\n<p style=\"text-align: left;\"><strong><img loading=\"lazy\" decoding=\"async\" class=\"alignright wp-image-9509\" src=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2020\/01\/Park200x200.jpg\" alt=\"\" width=\"144\" height=\"144\" srcset=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2020\/01\/Park200x200.jpg 200w, https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2020\/01\/Park200x200-150x150.jpg 150w\" sizes=\"(max-width: 144px) 100vw, 144px\" \/>Janvier 2020 :<\/strong> au Dr Bum-Joon Park, PhD, Universit\u00e9 nationale de Pusan, R\u00e9publique de Cor\u00e9e. \u00ab Effet de la prog\u00e9rinine (SLC-D011) et du lonafarnib sur le HGPS : une \u00e9tude combin\u00e9e in vitro et in vivo \u00bb<\/p>\n<p>Le Dr Park a mis au point un m\u00e9dicament appel\u00e9 prog\u00e9rinine qui inhibe la prog\u00e9rinine et inhibe la maladie dans les cellules prog\u00e9ria chez la souris. Le Dr Park va maintenant \u00e9tudier les effets synerg\u00e9tiques de la prog\u00e9rinine et du lonafarnib. Il comparera un traitement \u00e0 m\u00e9dicament unique (lonafarnib) et un traitement combin\u00e9 (prog\u00e9rinine et lonafarnib) pour d\u00e9terminer lequel est le plus efficace. Si la combinaison de m\u00e9dicaments pr\u00e9sente une faible toxicit\u00e9, un essai clinique combin\u00e9 de prog\u00e9rinine et de lonafarnib pourrait \u00eatre \u00e0 l&#039;horizon !<\/p>\n<p>[\/et_pb_text][et_pb_text admin_label=\u201d2020-4\u2033 module_id=\u201d2020-4\u2033 _builder_version=\u201d4.16\u2033 min_height=\u201d244px\u201d global_colors_info=\u201d{}\u201d]<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2021\/02\/Dr.-Liu-Photo-1.jpg\" width=\"144\" height=\"144\" alt=\"\" class=\"wp-image-12150 aligncenter size-full\" style=\"float: right;\" \/><strong>Janvier 2020 : <\/strong>\u00c0 David R. Liu, PhD, professeur Richard Merkin et directeur du Merkin Institute of Transformative Technologies in Healthcare, directeur du programme de biologie chimique et de sciences th\u00e9rapeutiques, membre principal de l&#039;Institut et vice-pr\u00e9sident de la facult\u00e9, Broad Institute, chercheur, Howard Hughes Medical Institute, professeur Thomas Dudley Cabot de sciences naturelles et professeur de chimie et de biologie chimique, Universit\u00e9 de Harvard. \u00ab Traitements d&#039;\u00e9dition de base pour HGPS \u00bb.<\/p>\n<p>Le laboratoire du Dr Liu effectuera des tests et la validation de nouvelles variantes d&#039;\u00e9diteur de base pour corriger l&#039;all\u00e8le pathog\u00e8ne G608G en LMNA de type sauvage, le d\u00e9veloppement et la production de virus pour d\u00e9livrer cet \u00e9diteur et l&#039;ARN guide appropri\u00e9 dans les cellules d\u00e9riv\u00e9es des patients, le d\u00e9veloppement et la production des virus pour d\u00e9livrer cet \u00e9diteur et l&#039;ARN guide appropri\u00e9 in vivo, les analyses d&#039;ADN hors cible et d&#039;ARN hors cible, les analyses d&#039;ARN et de prot\u00e9ines des cellules d\u00e9riv\u00e9es des patients trait\u00e9es, et le soutien aux exp\u00e9riences et analyses suppl\u00e9mentaires n\u00e9cessaires<strong><br \/> <\/strong><\/p>\n<p>[\/et_pb_text][et_pb_text admin_label=\u201d2019-3\u2033 module_id=\u201d2019-3\u2033 _builder_version=\u201d4.16\u2033 custom_padding=\u201d||37px|||\u201d global_colors_info=\u201d{}\u201d]<strong><img loading=\"lazy\" decoding=\"async\" class=\"alignright wp-image-8084\" src=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2019\/08\/Abby-Buchwalter_1000x1000.jpg\" alt=\"\" width=\"144\" height=\"144\" srcset=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2019\/08\/Abby-Buchwalter_1000x1000.jpg 300w, https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2019\/08\/Abby-Buchwalter_1000x1000-150x150.jpg 150w\" sizes=\"(max-width: 144px) 100vw, 144px\" \/>D\u00e9cembre 2019 : <\/strong>Le Dr Abigail Buchwalter est professeure adjointe \u00e0 l&#039;Institut de recherche cardiovasculaire et au D\u00e9partement de physiologie de l&#039;Universit\u00e9 de Californie \u00e0 San Francisco. Les projets du laboratoire Buchwalter s&#039;articulent autour de la d\u00e9finition des m\u00e9canismes qui r\u00e9gissent l&#039;\u00e9tablissement, la sp\u00e9cialisation et le maintien de l&#039;organisation nucl\u00e9aire dans les diff\u00e9rents types de cellules. Le r\u00f4le de la lame nucl\u00e9aire dans l&#039;organisation du g\u00e9nome au sein du noyau et la d\u00e9finition de la fa\u00e7on dont cet ordre est perturb\u00e9 par les mutations li\u00e9es \u00e0 la maladie sont particuli\u00e8rement int\u00e9ressants.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2019-2\u2033 module_id=\u201d2017-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<\/p>\n<p><strong><img loading=\"lazy\" decoding=\"async\" class=\"alignright wp-image-8085\" src=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2019\/08\/CLS-915x1024.jpg\" alt=\"\" width=\"144\" height=\"161\" srcset=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2019\/08\/CLS-915x1024.jpg 915w, https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2019\/08\/CLS-268x300.jpg 268w, https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2019\/08\/CLS-768x859.jpg 768w, https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2019\/08\/CLS-1080x1209.jpg 1080w\" sizes=\"(max-width: 144px) 100vw, 144px\" \/>Octobre 2019 : <\/strong>Le Dr Stewart est un chercheur tr\u00e8s exp\u00e9riment\u00e9 dans le domaine de la recherche sur la prog\u00e9ria. Au cours de la derni\u00e8re d\u00e9cennie, ses recherches se sont concentr\u00e9es sur les laminopathies, un ensemble h\u00e9t\u00e9rog\u00e8ne de maladies r\u00e9sultant toutes de mutations du g\u00e8ne LaminA qui affectent le vieillissement, la fonction cardiovasculaire et la dystrophie musculaire. Lui et ses coll\u00e8gues ont montr\u00e9 que la suppression d&#039;une prot\u00e9ine appel\u00e9e SUN1 inverse la perte de poids et augmente la survie chez les souris atteintes de la prog\u00e9ria. Il va maintenant effectuer un d\u00e9pistage de m\u00e9dicaments bas\u00e9 sur cette d\u00e9couverte, en examinant des milliers de produits chimiques pour tout ce qui pourrait perturber SUN1 et pourrait potentiellement servir de nouveau m\u00e9dicament pour traiter les enfants atteints de prog\u00e9ria.\u00a0\u00a0<\/p>\n<p>[\/et_pb_text][et_pb_text admin_label=\u201d2019-1\u2033 module_id=\u201d2017-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-8160 alignright\" src=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2019\/08\/Bergo2x2.jpg\" alt=\"\" width=\"144\" height=\"144\" \/>Novembre 2017 :\u00a0<\/strong>au Dr Martin Berg\u00f6, PhD, professeur de biosciences, Institut Karolinska, Stockholm. \u00ab D\u00e9veloppement et tests pr\u00e9cliniques d&#039;inhibiteurs de l&#039;ICMT pour la th\u00e9rapie HGPS. \u00bb Les recherches du Dr Berg\u00f6 sont bas\u00e9es sur la d\u00e9couverte que la r\u00e9duction de l&#039;ICMT, une enzyme n\u00e9cessaire au traitement de la prog\u00e9rine, inverse de nombreuses caract\u00e9ristiques pathologiques chez les souris d\u00e9ficientes en Zmpste24, de type prog\u00e9ria. Ses \u00e9tudes pr\u00e9liminaires montrent que les cellules Progeria cultiv\u00e9es en laboratoire se d\u00e9veloppent plus rapidement et plus longtemps lorsqu&#039;elles sont trait\u00e9es avec des inhibiteurs de l&#039;ICMT. Le Dr Berg\u00f6 testera des m\u00e9dicaments qui bloquent cette enzyme, et donc potentiellement la production de prog\u00e9rine, en cherchant \u00e0 savoir si les mod\u00e8les de souris Progeria deviennent plus sains et vivent plus longtemps lorsqu&#039;ils sont trait\u00e9s avec ce type de m\u00e9dicament.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2017-1\u2033 module_id=\u201d2017-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Novembre 2017 :\u00a0<\/strong>au Dr Richard K. Assoian, PhD, professeur, Universit\u00e9 de Pennsylvanie, Philadelphie, PA. \u00ab Analyse et att\u00e9nuation de\u00a0<img loading=\"lazy\" decoding=\"async\" class=\"alignright wp-image-3637\" src=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2017\/03\/Assoian.jpg\" sizes=\"(max-width: 150px) 100vw, 150px\" srcset=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2017\/03\/Assoian.jpg 200w, https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2017\/03\/Assoian-78x100.jpg 78w\" alt=\"\" width=\"150\" height=\"192\" \/>Le Dr Assoian pense que leurs recherches permettront de d\u00e9terminer pourquoi les art\u00e8res atteintes de HGPS se raidissent pr\u00e9matur\u00e9ment et si ce raidissement art\u00e9riel pr\u00e9matur\u00e9 peut \u00eatre \u00e9vit\u00e9, soit par un traitement pharmacologique, soit par une modification g\u00e9n\u00e9tique des souris. Le Dr Richard Assoian a re\u00e7u sa formation \u00e0 l&#039;Universit\u00e9 Johns Hopkins (BA), \u00e0 l&#039;Universit\u00e9 de Chicago (PhD) et aux National Institutes of Health (post-doctorat). Il a fait partie des facult\u00e9s de l&#039;Universit\u00e9 Columbia et de l&#039;Universit\u00e9 de Miami avant de rejoindre l&#039;Universit\u00e9 de Pennsylvanie en 1998. Il est actuellement professeur de pharmacologie au D\u00e9partement de pharmacologie des syst\u00e8mes et de th\u00e9rapeutique translationnelle de la Facult\u00e9 de m\u00e9decine. Le laboratoire du Dr Assoian \u00e9tudie comment les changements dans la rigidit\u00e9 de la matrice extracellulaire art\u00e9rielle affectent la fonction des cellules musculaires lisses art\u00e9rielles. Dans cette \u00e9tude actuelle, son laboratoire utilisera un mod\u00e8le de souris Progeria pour \u00e9tudier la base et les cons\u00e9quences du raidissement art\u00e9riel pr\u00e9matur\u00e9 dans le HGPS.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2017-2\u2033 module_id=\u201d2017-2\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Septembre 2017 (date de d\u00e9but octobre 2017) :\u00a0<\/strong>Au Dr Toren Finkel, MD\/PhD, directeur de l&#039;Aging Institute, Pittsburgh, PA. \u00ab Autophagie vasculaire et progression du syndrome de Guillain-Barr\u00e9 \u00bb.<strong><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-3028 alignright\" src=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2017\/03\/T_Finkel-2a.jpg\" sizes=\"(max-width: 125px) 100vw, 125px\" srcset=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2017\/03\/T_Finkel-2a.jpg 125w, https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2017\/03\/T_Finkel-2a-69x100.jpg 69w\" alt=\"\" width=\"125\" height=\"181\" \/><\/strong><\/p>\n<p>Le Dr Finkel tente de comprendre pourquoi le syndrome de Horton-Hypertrophie vasculaire (HGPS) est une prog\u00e9ria segmentaire, c&#039;est-\u00e0-dire pourquoi il semble affecter certains tissus plus que d&#039;autres. Il s&#039;int\u00e9resse particuli\u00e8rement aux causes des probl\u00e8mes vasculaires. On pense que cette nature segmentaire de la maladie pourrait \u00eatre due au fait que la cellule qui contribue \u00e0 la formation des vaisseaux sanguins, la cellule musculaire lisse vasculaire, pourrait r\u00e9agir l\u00e9g\u00e8rement diff\u00e9remment \u00e0 l&#039;expression de la prog\u00e9rine par rapport aux autres types de cellules. Cette diff\u00e9rence est li\u00e9e \u00e0 une autre prot\u00e9ine appel\u00e9e p62, qui intervient dans le processus cellulaire d&#039;autophagie. Il pense que la prot\u00e9ine p62 se comporte diff\u00e9remment dans les cellules musculaires lisses par rapport aux autres cellules (dans les cellules musculaires lisses, elle semble se localiser dans le noyau cellulaire) et que ces diff\u00e9rences pourraient expliquer pourquoi les vaisseaux sanguins pr\u00e9sentent tant de probl\u00e8mes dans le syndrome de Horton-Hypertrophie vasculaire. Il pense \u00e9galement qu&#039;il est possible de d\u00e9velopper des m\u00e9dicaments qui agissent sur la prot\u00e9ine p62 et que ces m\u00e9dicaments pourraient \u00eatre utiles pour traiter les patients atteints de syndrome de Horton-Hypertrophie vasculaire.<\/p>\n<p>Toren Finkel est directeur de l&#039;Aging Institute de l&#039;Universit\u00e9 de Pittsburgh\/UPMC et titulaire de la chaire G. Nicholas Beckwith III et Dorothy B. Beckwith en m\u00e9decine translationnelle au d\u00e9partement de m\u00e9decine de l&#039;Universit\u00e9 de Pittsburgh. Il a obtenu son dipl\u00f4me de premier cycle en physique et son doctorat en m\u00e9decine et en cardiologie \u00e0 la Harvard Medical School en 1986. Apr\u00e8s une r\u00e9sidence en m\u00e9decine interne au Massachusetts General Hospital, il a effectu\u00e9 une bourse de recherche en cardiologie \u00e0 la Johns Hopkins Medical School. En 1992, il est arriv\u00e9 au NIH en tant que chercheur au sein du programme de recherche intramuros du National Heart, Lung and Blood Institute (NHLBI). Au cours de son s\u00e9jour au NIH, il a occup\u00e9 divers postes, notamment celui de chef de la branche de cardiologie et de chef du centre de m\u00e9decine mol\u00e9culaire au sein du NHLBI. Il est membre de l&#039;American Society for Clinical Research (ASCR), de l&#039;Association of American Physicians (AAP) et membre de l&#039;American Association for the Advancement of Science (AAAS). Il si\u00e8ge \u00e0 de nombreux comit\u00e9s de r\u00e9daction, notamment au comit\u00e9 de r\u00e9daction de\u00a0<em>Science<\/em>Bien que les fonds intramuros du NIH aient principalement soutenu son travail, son laboratoire a re\u00e7u le soutien de la Fondation m\u00e9dicale Ellison en tant que chercheur principal et de la Fondation Leducq, o\u00f9 il est actuellement coordinateur am\u00e9ricain d&#039;un r\u00e9seau transatlantique \u00e9tudiant la r\u00e9g\u00e9n\u00e9ration cardiaque. Ses recherches actuelles portent sur le r\u00f4le de l&#039;autophagie, des esp\u00e8ces r\u00e9actives de l&#039;oxyg\u00e8ne et de la fonction mitochondriale dans le vieillissement et les maladies li\u00e9es \u00e0 l&#039;\u00e2ge.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2016-1\u2033 module_id=\u201d2016-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2016 (date de d\u00e9but 1er f\u00e9vrier 2017) :<\/strong>\u00a0\u00c0 Juan Carlos Belmonte Izpisua, Ph. D., professeur, Laboratoires d&#039;expression g\u00e9n\u00e9tique \u00e0 l&#039;\u00a0<a title=\"Institut Salk d&#039;\u00e9tudes biologiques\" href=\"https:\/\/en.wikipedia.org\/wiki\/Salk_Institute_for_Biological_Studies\">Institut Salk d&#039;\u00e9tudes biologiques<\/a>, La Jolla, CA, USA. Il est l&#039;ancien directeur et a aid\u00e9 \u00e0 \u00e9tablir le\u00a0<a title=\"es:Centro de Medicina Regenerativa de Barcelone\" href=\"https:\/\/es.wikipedia.org\/wiki\/Centro_de_Medicina_Regenerativa_de_Barcelona\">Centre de M\u00e9decine R\u00e9g\u00e9n\u00e9rative de Barcelone<\/a>Il est titulaire d&#039;un doctorat en biochimie et pharmacologie de l&#039;Universit\u00e9 de Bologne, en Italie, et de l&#039;Universit\u00e9 de Valence, en Espagne. Il est chercheur postdoctoral au Laboratoire europ\u00e9en de biologie mol\u00e9culaire (EMBL) de l&#039;Universit\u00e9 de Marbourg, \u00e0 Heidelberg, en Allemagne, et \u00e0 l&#039;UCLA, aux \u00c9tats-Unis. \u00ab Am\u00e9lioration des ph\u00e9notypes de vieillissement pr\u00e9matur\u00e9 dans le syndrome de Hutchinson-Gilford Progeria. \u00bb<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/JuanCarlosIzpisuaBelmonte1.jpg\" width=\"125\" height=\"165\" \/>Les alt\u00e9rations cardiovasculaires sont la principale cause de d\u00e9c\u00e8s chez les patients atteints de Progeria. Le laboratoire du Dr Izpisua Belmonte a d\u00e9montr\u00e9 que la reprogrammation cellulaire peut rajeunir les cellules de Progeria. Son laboratoire utilise d\u00e9sormais la reprogrammation cellulaire pour am\u00e9liorer les ph\u00e9notypes de vieillissement dans des mod\u00e8les murins de Progeria, en mettant l&#039;accent sur le syst\u00e8me cardiovasculaire. Ces d\u00e9couvertes pourraient conduire au d\u00e9veloppement de nouveaux traitements pour les patients atteints de Progeria.<\/p>\n<p>Le domaine de recherche du Dr Izpisua Belmonte est ax\u00e9 sur la compr\u00e9hension de la biologie des cellules souches, du d\u00e9veloppement et de la r\u00e9g\u00e9n\u00e9ration des organes et des tissus. Il a publi\u00e9 plus de 350 articles dans des revues \u00e0 comit\u00e9 de lecture et des chapitres de livres de grande envergure, reconnus \u00e0 l&#039;\u00e9chelle internationale. Il a re\u00e7u plusieurs distinctions et prix notables, notamment le William Clinton Presidential Award, le Pew Scholar Award, le National Science Foundation Creativity Award, le American Heart Association Established Investigator Award et la chaire Nobel Roger Guillemin pour ses efforts dans ces domaines. Au fil des ans, ses travaux ont contribu\u00e9 \u00e0 d\u00e9couvrir le r\u00f4le de certains g\u00e8nes hom\u00e9obox dans la structuration et la sp\u00e9cification des organes et des tissus, ainsi qu&#039;\u00e0 l&#039;identification des m\u00e9canismes mol\u00e9culaires qui d\u00e9terminent la mani\u00e8re dont les diff\u00e9rents pr\u00e9curseurs de types cellulaires des organes internes sont organis\u00e9s spatialement le long de l&#039;axe gauche-droit embryonnaire. Ses travaux contribuent \u00e0 nous donner un aper\u00e7u des bases mol\u00e9culaires impliqu\u00e9es dans la r\u00e9g\u00e9n\u00e9ration des organes chez les vert\u00e9br\u00e9s sup\u00e9rieurs, la diff\u00e9renciation des cellules souches humaines en divers tissus ainsi que le vieillissement et les maladies li\u00e9es au vieillissement. Le but ultime de ses recherches est le d\u00e9veloppement de nouvelles mol\u00e9cules et de traitements sp\u00e9cifiques \u00e0 base de g\u00e8nes et de cellules pour gu\u00e9rir les maladies affectant l\u2019humanit\u00e9.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2016-2\u2033 module_id=\u201d2016-2\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<\/p>\n<p class=\"justifyleft\"><strong>D\u00e9cembre 2016 (date de d\u00e9but 1er f\u00e9vrier 2017) :\u00a0<\/strong>\u00c0 Ricardo Villa-Bellosta, Ph. D., chef d\u2019\u00e9quipe, Institut de recherche en sant\u00e9 de l\u2019h\u00f4pital universitaire de la Fondation Jim\u00e9nez D\u00edaz (FIIS-FJD, Espagne). \u00ab Strat\u00e9gies th\u00e9rapeutiques pour r\u00e9tablir l\u2019hom\u00e9ostasie normale des pyrophosphates dans les HGPS. \u00bb<\/p>\n<p><b><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/RicardoVillaBellosta.jpg\" width=\"125\" height=\"180\" \/><\/b>Comme les patients HGPS, Lmna<sup>G609G\/+<\/sup>\u00a0Les souris pr\u00e9sentent une calcification vasculaire excessive due \u00e0 une capacit\u00e9 alt\u00e9r\u00e9e du corps \u00e0 synth\u00e9tiser du pyrophosphate extracellulaire (PPi). \u00c9tant donn\u00e9 qu&#039;un d\u00e9s\u00e9quilibre entre la d\u00e9gradation et la synth\u00e8se du PPi extracellulaire peut \u00e9galement entra\u00eener une calcification pathologique du cartilage articulaire et d&#039;autres tissus mous, la diminution syst\u00e9mique du PPi circulant associ\u00e9e \u00e0 l&#039;expression de la prog\u00e9rine pourrait expliquer plusieurs manifestations cliniques du HGPS, notamment la calcification vasculaire et les anomalies osseuses et articulaires. Le traitement par PPi exog\u00e8ne a r\u00e9duit la calcification vasculaire mais n&#039;a pas augment\u00e9 la dur\u00e9e de vie des Lmna<sup>G609G\/G609G<\/sup>\u00a0souris. Cela est d\u00fb \u00e0 l&#039;hydrolyse rapide du PPi exog\u00e8ne au niveau s\u00e9rique basal, ce qui r\u00e9duit le temps d&#039;action du PPi pour emp\u00eacher la calcification ectopique dans d&#039;autres tissus mous tels que les articulations. R\u00e9tablissement de l&#039;hom\u00e9ostasie correcte du PPi dans Lmna<sup>G609G\/+<\/sup>L&#039;utilisation d&#039;inhibiteurs pharmacologiques des enzymes impliqu\u00e9es dans le m\u00e9tabolisme extracellulaire du pyrophosphate chez des souris pourrait am\u00e9liorer \u00e0 la fois leur qualit\u00e9 et leur dur\u00e9e de vie.<\/p>\n<p>Ricardo Villa-Bellosta a obtenu son doctorat en 2010 \u00e0 l&#039;Universit\u00e9 de Saragosse (Espagne). Son travail de doctorat a port\u00e9 sur le r\u00f4le des transporteurs de phosphate dans la calcification vasculaire, la physiologie r\u00e9nale et la toxicocin\u00e9tique de l&#039;arsenic. Pour ses travaux, il a re\u00e7u plusieurs prix, dont le Prix de doctorat extraordinaire, le Prix de l&#039;Acad\u00e9mie royale espagnole des m\u00e9decins et le Prix de recherche Enrique Coris. Il a \u00e9t\u00e9 chercheur invit\u00e9 \u00e0 la Facult\u00e9 de m\u00e9decine de l&#039;Universit\u00e9 Emory \u00e0 Atlanta (\u00c9tats-Unis), o\u00f9 il a \u00e9tudi\u00e9 le m\u00e9tabolisme du pyrophosphate extracellulaire (ePPi) dans la paroi aortique. En 2012, il a rejoint le Centro Nacional de Investigaciones Cardiovasculares (CNIC, Espagne) en tant que chercheur postdoctoral Juan de la Cierva, concentrant ses travaux sur le m\u00e9tabolisme de l&#039;ePPi \u00e0 la fois dans la calcification des plaques d&#039;ath\u00e9rome et dans la calcification vasculaire chez les souris HGPS. En 2015, il a rejoint l&#039;Institut de recherche en sant\u00e9 de l&#039;h\u00f4pital universitaire de la Fondation Jim\u00e9nez D\u00edaz (FIIS-FJD, Espagne) pour \u00e9tudier l&#039;hom\u00e9ostasie phosphate\/pyrophosphate chez les patients h\u00e9modialys\u00e9s en tant que chercheur postdoctoral Sara Borrell. En septembre 2015, il a re\u00e7u une bourse \u00ab I+D+I Young Researchers \u00bb en tant que chef d&#039;\u00e9quipe au FIIS-FJD pour \u00e9tudier le r\u00f4le du m\u00e9tabolisme de l&#039;ePPi sur la calcification vasculaire dans les maladies r\u00e9nales chroniques et le diab\u00e8te.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2016-3\u2033 module_id=\u201d2016-3\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2016 (date de d\u00e9but 1er f\u00e9vrier 2017) :<\/strong>\u00a0\u00c0 Isabella Saggio, PhD, professeure agr\u00e9g\u00e9e de g\u00e9n\u00e9tique et de th\u00e9rapie g\u00e9nique, Universit\u00e9 Sapienza (Rome, Italie). \u00ab La prot\u00e9ine t\u00e9lom\u00e9rique interagissant avec la lamine AKTIP dans le HGPS. \u00bb<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/saggio-photo-2016.jpg\" width=\"125\" height=\"136\" \/>La mutation causale du HGPS affecte la lamine A. AKTIP, une prot\u00e9ine que nous avons r\u00e9cemment caract\u00e9ris\u00e9e, est un facteur d&#039;interaction avec la lamine essentiel \u00e0 la survie cellulaire, impliqu\u00e9 dans le m\u00e9tabolisme des t\u00e9lom\u00e8res et de l&#039;ADN. Quatre observations principales relient cette nouvelle prot\u00e9ine au HGPS : i) l&#039;alt\u00e9ration de l&#039;AKTIP r\u00e9capitule les caract\u00e9ristiques du HGPS dans les cellules ; ii) l&#039;alt\u00e9ration de l&#039;AKTIP r\u00e9capitule les caract\u00e9ristiques du HGPS chez la souris ; iii) l&#039;AKTIP interagit avec les lamines et iv) l&#039;AKTIP est alt\u00e9r\u00e9 dans les cellules HGPS d\u00e9riv\u00e9es de patients. Dans nos \u00e9tudes, nous postulons l&#039;hypoth\u00e8se qu&#039;un complexe AKTIP agit comme un point de contr\u00f4le pour les \u00e9v\u00e9nements r\u00e9plicatifs de l&#039;ADN difficiles. Nous pensons que dans le HGPS, ce point de contr\u00f4le est compromis, ce qui, \u00e0 son tour, peut contribuer au ph\u00e9notype HGPS. Nous proposons d&#039;analyser en profondeur la fonction d&#039;AKTIP in vitro et chez la souris. Nous esp\u00e9rons que cette recherche apportera de nouvelles perspectives sur le lien entre la prog\u00e9rine et le dysfonctionnement des t\u00e9lom\u00e8res gr\u00e2ce \u00e0 AKTIP, ainsi que des informations sur le r\u00f4le de l&#039;alt\u00e9ration de la r\u00e9plication de l&#039;ADN en tant que m\u00e9canisme moteur potentiel de la prog\u00e9ria. \u00c9tant donn\u00e9 que la connaissance des d\u00e9terminants et des m\u00e9canismes moteurs de l&#039;\u00e9tiologie du HGPS n&#039;est pas encore enti\u00e8rement acquise, nous pensons que les \u00e9tudes sur de nouveaux acteurs interagissant avec la lamine, tels qu&#039;AKTIP, seront d\u00e9terminantes pour d\u00e9cortiquer les bases m\u00e9canistiques du HGPS et ouvrir la voie \u00e0 de nouvelles strat\u00e9gies th\u00e9rapeutiques.<\/p>\n<p>Isabella Saggio a obtenu son doctorat en g\u00e9n\u00e9tique \u00e0 l&#039;Universit\u00e9 Sapienza (Rome, Italie). Elle a travaill\u00e9 \u00e0 l&#039;Institut de recherche Merck pour la biologie mol\u00e9culaire (Rome, Italie) de 1991 \u00e0 1994. De 1994 \u00e0 1997, elle a \u00e9t\u00e9 chercheuse postdoctorale europ\u00e9enne \u00e0 l&#039;IGR (Paris, France). En 1998, elle est revenue \u00e0 l&#039;Universit\u00e9 Sapienza, d&#039;abord comme assistante de recherche, puis comme professeure associ\u00e9e de g\u00e9n\u00e9tique et de th\u00e9rapie g\u00e9nique. Les principaux int\u00e9r\u00eats de recherche d&#039;IS sont la th\u00e9rapie g\u00e9nique ainsi que les \u00e9tudes sur les t\u00e9lom\u00e8res et le vieillissement. IS a \u00e9t\u00e9 membre du Parc scientifique de San Raffaele de 2003 \u00e0 2011, fait partie du CNR depuis 2003, du R\u00e9seau italien pour les laminopathies depuis 2016. IS est le repr\u00e9sentant de Sapienza au sein du r\u00e9seau interuniversitaire de biotechnologie en Italie, coordonne les activit\u00e9s internationales \u00e0 Sapienza et a fond\u00e9 en 2016 un Master de journalisme scientifique pour am\u00e9liorer les relations entre les chercheurs et le public (<a href=\"https:\/\/www.mastersgp.it\/\">www.mastersgp.it<\/a>). Les activit\u00e9s du SI sont d\u00e9crites sur le site :\u00a0<a href=\"https:\/\/www.saggiolab.com\/\">www.saggiolab.com<\/a>.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2016-4\u2033 module_id=\u201d2016-4\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2016 (date de d\u00e9but 1er mars 2017) :\u00a0<\/strong>\u00c0 Tom Misteli, PhD, chercheur \u00e9m\u00e9rite du NIH et directeur du Centre de recherche sur le cancer du National Cancer Institute, NIH. \u00ab Tests in vivo de candidats traitements HGPS. \u00bb<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Misteliportrait-(1).jpg\" width=\"125\" height=\"146\" \/>Notre objectif est de tester in vivo de nouveaux agents th\u00e9rapeutiques potentiels contre la prog\u00e9ria. Ce projet hautement collaboratif repose sur la d\u00e9couverte dans le laboratoire de Tom Misteli de plusieurs agents th\u00e9rapeutiques candidats, le d\u00e9veloppement d&#039;un mod\u00e8le animal HGPS dans le laboratoire de Carlos Lopez-Otin et l&#039;expertise d&#039;Alicia Rodriguez-Folgueras dans le test de divers compos\u00e9s dans un contexte in vivo.<\/p>\n<p>Tom Misteli est chercheur \u00e9m\u00e9rite du NIH et directeur du Centre de recherche sur le cancer du National Cancer Institute du NIH. C&#039;est un biologiste cellulaire de renomm\u00e9e internationale qui a \u00e9t\u00e9 le pionnier de l&#039;utilisation des approches d&#039;imagerie pour \u00e9tudier les g\u00e9nomes et l&#039;expression des g\u00e8nes dans les cellules vivantes. L&#039;int\u00e9r\u00eat de son laboratoire est de d\u00e9couvrir les principes fondamentaux de l&#039;organisation et de la fonction du g\u00e9nome en 3D et d&#039;appliquer ces connaissances au d\u00e9veloppement de nouvelles strat\u00e9gies diagnostiques et th\u00e9rapeutiques pour le cancer et le vieillissement. Il a obtenu son doctorat \u00e0 l&#039;Universit\u00e9 de Londres, au Royaume-Uni, et a effectu\u00e9 une formation postdoctorale au Cold Spring Harbor Laboratory. Pour son travail, il a re\u00e7u de nombreux prix, notamment le prix Herman Beerman, la m\u00e9daille Wilhelm Bernhard, la m\u00e9daille d&#039;or de l&#039;Universit\u00e9 Charles, le prix Flemming, le prix Gian-Tondury, le prix du directeur du NIH et un prix du m\u00e9rite du NIH. Il agit en tant que conseiller pour de nombreuses agences nationales et internationales et si\u00e8ge \u00e0 plusieurs comit\u00e9s de r\u00e9daction, notamment\u00a0<i>Cellule, Science\u00a0<\/i>et<i>\u00a0PLoS Biologie.\u00a0\u00a0<\/i>Il est le<i>\u00a0<\/i>R\u00e9dacteur en chef de\u00a0<i>Opinion actuelle en biologie cellulaire.<\/i><br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2016-5\u2033 module_id=\u201d2016-5\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Ao\u00fbt 2016 (date de d\u00e9but 1er janvier 2017) :\u00a0<\/strong>\u00c0 Silvia Ortega-Guti\u00e9rrez. Professeure associ\u00e9e depuis 2013, boursi\u00e8re Ram\u00f3n y Cajal, d\u00e9partement de chimie organique 2008-2012, PhD, 2004, Universidad Complutense de Madrid, Espagne. Elle a travaill\u00e9 sous la supervision de la professeure Mar\u00eda Luz L\u00f3pez-Rodr\u00edguez, boursi\u00e8re Fulbright du d\u00e9partement de chimie m\u00e9dicinale, laboratoire du professeur Ben Cravatt, biologie chimique et prot\u00e9omique, Scripps Research Institute en Californie, \u00c9tats-Unis ; \u00ab Nouveaux inhibiteurs de l&#039;isopr\u00e9nylcyst\u00e9ine carboxym\u00e9thyltransf\u00e9rase (ICMT) pour le traitement de la prog\u00e9ria \u00bb<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Ortega-Gutierrez-Siliva-cr---photo.jpg\" width=\"125\" height=\"133\" \/>Dans ce projet, nous proposons le d\u00e9veloppement de nouveaux inhibiteurs de l&#039;isopr\u00e9nylcyst\u00e9ine carboxym\u00e9thyltransf\u00e9rase (ICMT) pour le traitement du syndrome de Hutchinson-Gilford Progeria (HGPS, ou progeria) sur la base d&#039;un hit pr\u00e9c\u00e9demment identifi\u00e9 dans notre laboratoire de recherche. Ce hit (UCM-13239) inhibe de mani\u00e8re significative l&#039;ICMT, induit une mauvaise localisation de la prot\u00e9ine prog\u00e9rine dans les fibroblastes prog\u00e9ro\u00efdes (LmnaG609G\/G609G), augmente la viabilit\u00e9 de ces cellules et favorise les voies de signalisation pro-survie dans les cellules trait\u00e9es. En utilisant ce compos\u00e9 comme point de d\u00e9part, notre \u00e9quipe r\u00e9alisera un programme de chimie m\u00e9dicinale (hit to lead et lead optimization) visant \u00e0 obtenir des compos\u00e9s am\u00e9lior\u00e9s en termes d&#039;activit\u00e9 biologique et de param\u00e8tres pharmacocin\u00e9tiques. Le ou les compos\u00e9s optimaux seront \u00e9valu\u00e9s pour leur efficacit\u00e9 dans un mod\u00e8le in vivo de progeria.<\/p>\n<p>Silvia Ortega-Guti\u00e9rrez a obtenu son doctorat \u00e0 l&#039;Universit\u00e9 Complutense de Madrid, sous la direction du professeur Mar\u00eda Luz L\u00f3pez-Rodr\u00edguez dans le domaine de la chimie m\u00e9dicinale. Elle a ensuite rejoint le laboratoire du professeur Ben Cravatt au Scripps Research Institute (Californie, \u00c9tats-Unis) pour travailler dans le domaine de la biologie chimique et de la prot\u00e9omique avec une bourse Fulbright. Entre 2008 et 2012, elle a \u00e9t\u00e9 boursi\u00e8re Ram\u00f3n y Cajal au d\u00e9partement de chimie organique de l&#039;Universit\u00e9 Complutense, o\u00f9 elle a \u00e9t\u00e9 promue professeure associ\u00e9e en 2013. C&#039;est le poste qu&#039;elle occupe actuellement.<\/p>\n<p>Fran\u00e7aisLes domaines d&#039;int\u00e9r\u00eat du Dr Ortega-Guti\u00e9rrez sont la chimie m\u00e9dicinale et la biologie chimique, et en particulier les domaines des syst\u00e8mes endog\u00e8nes cannabino\u00efdes et acides lysophosphatidiques, la validation de nouvelles cibles th\u00e9rapeutiques et le d\u00e9veloppement de sondes chimiques pour l&#039;\u00e9tude des r\u00e9cepteurs coupl\u00e9s aux prot\u00e9ines G. Ses travaux ont \u00e9t\u00e9 publi\u00e9s dans des revues prestigieuses telles que Science, Nature Neuroscience, Angewandte Chemie et le Journal of Medicinal Chemistry, ainsi que dans des brevets qui ont \u00e9t\u00e9 transf\u00e9r\u00e9s \u00e0 l&#039;industrie pharmaceutique. En 2011 et en 2016, elle a re\u00e7u le \u00ab Prix du deuxi\u00e8me prix du jeune chimiste m\u00e9dicinal dans le milieu universitaire \u00bb de la F\u00e9d\u00e9ration europ\u00e9enne de chimie m\u00e9dicinale et en 2012 le \u00ab Prix du jeune chercheur \u00bb de la Soci\u00e9t\u00e9 royale espagnole de chimie.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2016-6\u2033 module_id=\u201d2016-6\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Juillet 2016 (date de d\u00e9but 1er octobre 2016) :\u00a0<\/strong>\u00c0 Roland Foisner, PhD, professeur de biochimie \u00e0 l&#039;universit\u00e9 m\u00e9dicale de Vienne et directeur adjoint des laboratoires Max F. Perutz, Vienne, Autriche. Coordinateur scientifique de l&#039;ancien projet de r\u00e9seau europ\u00e9en EURO-Laminopathies et r\u00e9dacteur en chef de la revue Nucleus ; \u00ab Contribution du dysfonctionnement des cellules endoth\u00e9liales aux maladies cardiovasculaires dans la prog\u00e9ria et implications pour les cibles diagnostiques et th\u00e9rapeutiques. \u00bb<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Portrait_Foisner.jpg\" width=\"125\" height=\"152\" \/>Le syndrome de Hutchinson-Gilford progeria (HGPS) est une maladie g\u00e9n\u00e9tique rare, caus\u00e9e par une mutation dans\u00a0<i>LMNA<\/i>\u00a0et caract\u00e9ris\u00e9e par des sympt\u00f4mes graves ressemblant aux caract\u00e9ristiques du vieillissement pr\u00e9matur\u00e9, notamment une maladie cardiovasculaire qui conduit \u00e0 l&#039;ath\u00e9roscl\u00e9rose, \u00e0 l&#039;hypertension, \u00e0 l&#039;hypertrophie cardiaque et \u00e0 la mort par insuffisance cardiaque. Des \u00e9tudes ant\u00e9rieures sur des patients et des mod\u00e8les de souris HGPS ont r\u00e9v\u00e9l\u00e9 une perte progressive de cellules musculaires lisses dans les vaisseaux sanguins, mais le r\u00f4le des cellules endoth\u00e9liales dans le d\u00e9veloppement de maladies cardiovasculaires li\u00e9es au HGPS n&#039;a pas encore \u00e9t\u00e9 analys\u00e9, malgr\u00e9 le fait que la fonction alt\u00e9r\u00e9e des cellules endoth\u00e9liales constitue un facteur de risque majeur de maladie cardiovasculaire dans le vieillissement normal. Afin d&#039;\u00e9tudier la base mol\u00e9culaire de la pathologie du vieillissement cardiovasculaire et d&#039;\u00e9tudier comment l&#039;endoth\u00e9lium vasculaire vieilli contribue au HGPS, nous avons g\u00e9n\u00e9r\u00e9 un nouveau mod\u00e8le de souris exprimant le HGPS responsable\u00a0<i>LMNA\u00a0<\/i>Le produit du g\u00e8ne mutant est s\u00e9lectivement pr\u00e9sent dans le syst\u00e8me de cellules endoth\u00e9liales vasculaires. Nos analyses pr\u00e9liminaires des souris ont montr\u00e9 un retard de croissance, une augmentation de la fibrose cardiaque, une hypertrophie cardiaque, une \u00e9l\u00e9vation des marqueurs d&#039;hypertrophie et une mort pr\u00e9matur\u00e9e des souris mutantes, ressemblant au ph\u00e9notype cardiovasculaire HGPS. Dans ce projet, nous \u00e9tudierons les m\u00e9canismes mol\u00e9culaires, la mani\u00e8re dont le mutant\u00a0<i>LMNA\u00a0<\/i>Le produit du g\u00e8ne affecte les cellules endoth\u00e9liales des vaisseaux sanguins et la mani\u00e8re dont cela peut affecter la fonction cardiaque. Nous identifierons les composants pro-ath\u00e9rog\u00e8nes s\u00e9cr\u00e9t\u00e9s dans les cellules endoth\u00e9liales et les vaisseaux mutants et testerons comment cette voie peut affecter d&#039;autres tissus et cellules. Ce projet identifiera \u00e9galement des biomarqueurs potentiels pour les maladies cardiovasculaires li\u00e9es au HGPS dans le sang. Notre projet \u00e9tudie pour la premi\u00e8re fois le r\u00f4le de l&#039;endoth\u00e9lium vasculaire dans le d\u00e9veloppement des maladies cardiovasculaires dans le HGPS et identifiera de nouvelles voies et composants (pro-ath\u00e9rog\u00e8nes) comme cibles potentielles pour le diagnostic et le traitement.<\/p>\n<p>Roland Foisner est professeur d&#039;universit\u00e9 de biochimie \u00e0 l&#039;universit\u00e9 de m\u00e9decine de Vienne et directeur adjoint des laboratoires Max F. Perutz. Il a obtenu son doctorat (Dr. techn.) en biotechnologie \u00e0 l&#039;universit\u00e9 technique de Vienne, en Autriche, en 1984, a \u00e9t\u00e9 professeur adjoint puis professeur associ\u00e9 \u00e0 l&#039;universit\u00e9 de Vienne, et a \u00e9t\u00e9 nomm\u00e9 professeur titulaire au d\u00e9partement de biochimie m\u00e9dicale de l&#039;universit\u00e9 de m\u00e9decine de Vienne en 2002. De 1991 \u00e0 1992, il a suivi une formation postdoctorale au Scripps Research Institute de La Jolla, en Californie, aux \u00c9tats-Unis.<\/p>\n<p>Roland Foisner a \u00e9t\u00e9 coordinateur scientifique d&#039;EURO-Laminopathies, un projet de r\u00e9seau europ\u00e9en de chercheurs cliniciens et de chercheurs de base, visant \u00e0 analyser les m\u00e9canismes mol\u00e9culaires des maladies li\u00e9es aux laminopathies pour le d\u00e9veloppement de nouvelles approches th\u00e9rapeutiques. Il est r\u00e9dacteur en chef de la revue Nucleus, si\u00e8ge au comit\u00e9 de r\u00e9daction de plusieurs revues de biologie cellulaire, au conseil consultatif scientifique de projets europ\u00e9ens et aux comit\u00e9s d&#039;\u00e9valuation de plusieurs organismes de financement internationaux. Il a \u00e9t\u00e9 doyen des \u00e9tudes sup\u00e9rieures du programme de doctorat du Biocentre international de Vienne jusqu&#039;en 2007 et a si\u00e9g\u00e9 dans de nombreux comit\u00e9s de th\u00e8se nationaux et internationaux.<\/p>\n<p>Les recherches men\u00e9es dans le laboratoire de Roland Foisner portent sur la dynamique et les fonctions des lamines et des prot\u00e9ines de liaison aux lamines dans l&#039;organisation du noyau et de la chromatine, dans la r\u00e9gulation de l&#039;expression et de la signalisation des g\u00e8nes et dans les maladies g\u00e9n\u00e9tiques allant des dystrophies musculaires au vieillissement pr\u00e9matur\u00e9. Il a publi\u00e9 de nombreux articles importants \u00e9valu\u00e9s par des pairs, des revues invit\u00e9es et des chapitres de livres, et a donn\u00e9 de nombreux s\u00e9minaires invit\u00e9s lors de r\u00e9unions nationales et internationales.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2015-1\u2033 module_id=\u201d2015-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2015 (date de d\u00e9but 1er janvier 2016) :\u00a0<\/strong>\u00c0 Juan Carlos Belmonte Izpisua, PhD, professeur, Gene Expression Laboratories, The Salk Institute for Biological Studies, La Jolla, CA, USA ; \u00ab L&#039;utilisation de nouvelles technologies pour identifier et valider des compos\u00e9s th\u00e9rapeutiques potentiels pour le traitement du syndrome de Hutchinson-Gilford Progeria \u00bb<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Belmonte%2C-Juan-Carlos.jpg\" width=\"125\" height=\"148\" \/>Les alt\u00e9rations cardiovasculaires sont la principale cause de d\u00e9c\u00e8s chez les patients atteints de Progeria. Le laboratoire du Dr Belmonte a d\u00e9velopp\u00e9 de nouveaux mod\u00e8les pour l&#039;\u00e9tude de la Progeria bas\u00e9s sur l&#039;utilisation de cellules souches pluripotentes induites (iPSC) g\u00e9n\u00e9r\u00e9es \u00e0 partir de patients atteints de Progeria. Son laboratoire utilise d\u00e9sormais des cellules vasculaires produites \u00e0 partir de ces mod\u00e8les pour la d\u00e9couverte de nouveaux m\u00e9dicaments capables d&#039;am\u00e9liorer les alt\u00e9rations cardiovasculaires dans les mod\u00e8les humains et murins de Progeria. Ces d\u00e9couvertes pourraient conduire au d\u00e9veloppement de nouveaux traitements pour les patients atteints de Progeria.<\/p>\n<p>Le Dr Juan Carlos Belmonte Izpisua est professeur aux Laboratoires d&#039;expression g\u00e9n\u00e9tique de l&#039;Universit\u00e9\u00a0<a title=\"Institut Salk d&#039;\u00e9tudes biologiques\" href=\"https:\/\/en.wikipedia.org\/wiki\/Salk_Institute_for_Biological_Studies\">Institut Salk d&#039;\u00e9tudes biologiques<\/a>, La Jolla, CA, USA. Il est l&#039;ancien directeur et a aid\u00e9 \u00e0 \u00e9tablir le\u00a0<a title=\"es:Centro de Medicina Regenerativa de Barcelone\" href=\"https:\/\/es.wikipedia.org\/wiki\/Centro_de_Medicina_Regenerativa_de_Barcelona\">Centre de M\u00e9decine R\u00e9g\u00e9n\u00e9rative de Barcelone<\/a>Il est titulaire d&#039;un doctorat en biochimie et pharmacologie de l&#039;Universit\u00e9 de Bologne, en Italie, et de l&#039;Universit\u00e9 de Valence, en Espagne. Il est chercheur postdoctoral au Laboratoire europ\u00e9en de biologie mol\u00e9culaire (EMBL) de l&#039;Universit\u00e9 de Marbourg, \u00e0 Heidelberg, en Allemagne, et \u00e0 l&#039;UCLA, aux \u00c9tats-Unis.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2015-2\u2033 module_id=\u201d2015-2\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<b>D\u00e9cembre 2015 (date de d\u00e9but 1er mars 2016) :\u00a0<\/b><b>\u00a0<\/b>\u00c0 Jed William Fahey, Sc.D., directeur du Cullman Chemoprotection Center,\u00a0<i>Professeur adjoint,\u00a0<\/i>Universit\u00e9 Johns Hopkins, \u00c9cole de m\u00e9decine, D\u00e9partement de m\u00e9decine, Division de pharmacologie clinique, D\u00e9partement de pharmacologie et de sciences mol\u00e9culaires ; \u00c9cole de sant\u00e9 publique Bloomberg, D\u00e9partement de sant\u00e9 internationale, Centre de nutrition humaine ; \u00ab La capacit\u00e9 des isothiocyanates d&#039;origine v\u00e9g\u00e9tale \u00e0 surpasser l&#039;efficacit\u00e9 du sulforaphane, avec une toxicit\u00e9 r\u00e9duite pour les lign\u00e9es cellulaires de Progeria. \u00bb<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Fahey%2C-Jed-W.jpg\" width=\"172\" height=\"125\" \/>Une \u00e9tude r\u00e9cente men\u00e9e par d&#039;autres [Gabriel et al., 2015,\u00a0<i>Vieillissement cellulaire<\/i>\u00a0[14(1):78-91] a montr\u00e9 que l&#039;isothiocyanate sulforaphane (un compos\u00e9 phytochimique issu du brocoli) am\u00e9liorait le taux de croissance des cellules cultiv\u00e9es provenant d&#039;enfants atteints de prog\u00e9ria et augmentait une vari\u00e9t\u00e9 de biomarqueurs associ\u00e9s au syndrome. Nos travaux sur les isothiocyanates issus de plantes comestibles sugg\u00e8rent que certains de ces plus de cent compos\u00e9s \u00e9troitement apparent\u00e9s devraient avoir des fen\u00eatres th\u00e9rapeutiques plus larges (la fourchette entre la concentration efficace et la concentration toxique) et peut-\u00eatre des concentrations efficaces plus faibles que le sulforaphane. Nous allons tester cette hypoth\u00e8se.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2015-3\u2033 module_id=\u201d2015-3\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<b>Juin 2015 (date de d\u00e9but 1er juillet 2015) :\u00a0<\/b>\u00c0 Bum-Joon Park, PhD, pr\u00e9sident et professeur du d\u00e9partement de biologie mol\u00e9culaire, Universit\u00e9 nationale de Pusan, R\u00e9publique de Cor\u00e9e ; \u00ab Am\u00e9lioration de l&#039;effet th\u00e9rapeutique de JH4, inhibiteur de la liaison prog\u00e9rine-lamine A\/C, contre le syndrome de prog\u00e9ria.<b>&quot;<\/b><b><a id=\"Bum-Joon\"><\/a><\/b><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Park%2CBum-Joon(2).jpg\" width=\"125\" height=\"163\" \/>Nous avons r\u00e9cemment d\u00e9couvert de nouveaux produits chimiques qui bloquent l&#039;interaction entre la prog\u00e9rine et la lamine A\/C gr\u00e2ce au criblage d&#039;une biblioth\u00e8que chimique. Dans un mod\u00e8le de souris produisant de la prog\u00e9rine (<i>Lmna<sup>G609G\/G609G<\/sup><\/i>), notre produit chimique (JH4) peut prolonger la dur\u00e9e de vie ainsi qu&#039;am\u00e9liorer les ph\u00e9notypes de vieillissement, y compris le gain de poids corporel, l&#039;augmentation de la force musculaire et de la taille des organes. Malgr\u00e9 l&#039;effet \u00e9vident du JH4 sur\u00a0<i>Lmna<sup>poids\/G609G<\/sup><\/i>souris, cela ne peut durer que 4 semaines\u00a0<i>Lmna<sup>G609G\/G609G<\/sup><\/i>\u00a0La dur\u00e9e de vie des souris a \u00e9t\u00e9 am\u00e9lior\u00e9e, ce qui indique que l&#039;effet du JH4 n&#039;est pas suffisant pour \u00eatre utilis\u00e9 comme m\u00e9dicament th\u00e9rapeutique contre le syndrome de la prog\u00e9ria au stade actuel. De plus, il faut am\u00e9liorer l&#039;effet du JH4. Pour cela, nous allons r\u00e9aliser plusieurs essais pour am\u00e9liorer l&#039;effet du JH4. Tout d&#039;abord, nous allons modifier nos produits chimiques pour obtenir une forme plus hydrophile. En fait, le JH4 est tr\u00e8s hydrophobe, ce qui serait l&#039;une des raisons pour lesquelles nous ne pouvons pas augmenter la dose. \u00c0 ce propos, nous avons d\u00e9j\u00e0 obtenu un compos\u00e9 hydrophile (JH010), avec un effet cellulaire similaire \u00e0 celui du JH4. En effet, nos r\u00e9sultats r\u00e9cents ont montr\u00e9 qu&#039;une augmentation du JH4 (de 10 mg\/kg \u00e0 20 mg\/kg) pouvait augmenter la dur\u00e9e de vie de 16 semaines (traitement par porteur) \u00e0 24 semaines (en fait, les souris ayant re\u00e7u une injection de 20 mg\/kg \u00e9taient encore en vie). Pour am\u00e9liorer ce produit chimique, nous avons g\u00e9n\u00e9r\u00e9 des d\u00e9riv\u00e9s du JH010 et v\u00e9rifi\u00e9 l&#039;effet biologique. Deuxi\u00e8mement, nous allons fabriquer des nanoparticules qui d\u00e9livreront le JH010 plus efficacement \u00e0 tout le corps. En fait, ce travail a d\u00e9j\u00e0 commenc\u00e9. Gr\u00e2ce \u00e0 ces deux m\u00e9thodes, nous obtiendrons des produits chimiques am\u00e9lior\u00e9s li\u00e9s au JH4 et les testerons dans\u00a0<i>Lmna<sup>G609G\/G609G<\/sup><\/i>\u00a0Mod\u00e8le de souris (dur\u00e9e de vie, analyse histologique, toxicit\u00e9, pharmacodynamie et pharmacocin\u00e9tique). \u00c0 partir de ces \u00e9tudes, nous souhaitons proposer la meilleure m\u00e9thode de traitement du HGPS dans le mod\u00e8le de souris ainsi que chez les enfants atteints de HGPS.<\/p>\n<p>Le Dr Park a obtenu son doctorat en biologie du cancer \u00e0 l&#039;Universit\u00e9 de Cor\u00e9e. Il a effectu\u00e9 ses recherches postdoctorales \u00e0 l&#039;Institut national cor\u00e9en de la sant\u00e9 (KNIH) et \u00e0 l&#039;Universit\u00e9 nationale de S\u00e9oul. Depuis 2006, il travaille \u00e0 l&#039;Universit\u00e9 nationale de Pusan. Il est aujourd&#039;hui pr\u00e9sident du d\u00e9partement de biologie mol\u00e9culaire. Ses recherches portent sur l&#039;identification du r\u00e9seau de signalisation sp\u00e9cifique \u00e0 la maladie (cancer, HGPS, syndrome de Werner) et sur la recherche de nouveaux produits chimiques capables de bloquer l&#039;interaction prot\u00e9ine-prot\u00e9ine li\u00e9e \u00e0 la maladie pour les candidats m\u00e9dicaments.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2015-4\u2033 module_id=\u201d2015-4\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<b>Juin 2015 (date de d\u00e9but 1er septembre 2015) :\u00a0<\/b>\u00c0 John P. Cooke, MD, PhD, Joseph C. \u00ab Rusty \u00bb Walter et Carole Walter Looke, titulaire de la chaire pr\u00e9sidentielle distingu\u00e9e de recherche sur les maladies cardiovasculaires, pr\u00e9sidente et membre \u00e0 part enti\u00e8re du d\u00e9partement des sciences cardiovasculaires, Houston Methodist Research Institute, directrice du Center for Cardiovascular Regeneration, Houston Methodist DeBakey Heart and Vascular Center, Houston, TX ; \u00ab Th\u00e9rapie par t\u00e9lom\u00e9rase pour la prog\u00e9ria. \u00bb<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Cooke%2CJohn-P.jpg\" width=\"125\" height=\"187\" \/>Chez les enfants atteints de prog\u00e9ria, les vaisseaux sanguins vieillissent tr\u00e8s rapidement. Cela provoque une maladie vasculaire qui conduit \u00e0 une crise cardiaque et \u00e0 un accident vasculaire c\u00e9r\u00e9bral. Nous avons l\u2019intention de d\u00e9velopper une th\u00e9rapie qui inverse le vieillissement vasculaire chez ces enfants. Nous avons d\u00e9j\u00e0 montr\u00e9 que les cellules humaines \u00e2g\u00e9es peuvent \u00eatre rajeunies en les traitant avec un ARN messager modifi\u00e9 (ARNmm) codant pour la t\u00e9lom\u00e9rase. La t\u00e9lom\u00e9rase est une prot\u00e9ine qui \u00e9tend les t\u00e9lom\u00e8res sur les chromosomes.<\/p>\n<p>Les t\u00e9lom\u00e8res sont comme la pointe d\u2019un lacet de chaussure : ils maintiennent les chromosomes ensemble et les t\u00e9lom\u00e8res sont n\u00e9cessaires au fonctionnement normal des chromosomes. \u00c0 mesure que les cellules vieillissent, les t\u00e9lom\u00e8res raccourcissent et, \u00e0 un moment donn\u00e9, le chromosome ne fonctionne plus correctement. \u00c0 ce stade, la cellule devient s\u00e9nescente et ne peut plus prolif\u00e9rer. Les t\u00e9lom\u00e8res sont en quelque sorte notre horloge biologique. Chez les enfants atteints de prog\u00e9ria, les t\u00e9lom\u00e8res raccourcissent plus rapidement. Nous avons l\u2019intention de tester notre th\u00e9rapie sur des cellules d\u2019enfants atteints de prog\u00e9ria pour voir si nous pouvons allonger les t\u00e9lom\u00e8res, inverser le processus de vieillissement et rajeunir les cellules vasculaires. Si cette approche fonctionne, nous avons l\u2019intention de d\u00e9velopper la th\u00e9rapie en vue d\u2019essais cliniques sur ces enfants.<\/p>\n<p>Le Dr John P. Cooke a suivi une formation en m\u00e9decine cardiovasculaire et a obtenu un doctorat en physiologie \u00e0 la Mayo Clinic. Il a \u00e9t\u00e9 recrut\u00e9 \u00e0 la Harvard Medical School en tant que professeur adjoint de m\u00e9decine. En 1990, il a \u00e9t\u00e9 recrut\u00e9 \u00e0 l&#039;Universit\u00e9 de Stanford pour diriger le programme de biologie et de m\u00e9decine vasculaires, et a \u00e9t\u00e9 nomm\u00e9 professeur \u00e0 la division de m\u00e9decine cardiovasculaire de la facult\u00e9 de m\u00e9decine de l&#039;Universit\u00e9 de Stanford et directeur associ\u00e9 du Stanford Cardiovascular Institute jusqu&#039;\u00e0 son recrutement \u00e0 Houston Methodist en 2013.<\/p>\n<p>Le Dr Cooke a publi\u00e9 plus de 500 articles de recherche, documents de position, revues, chapitres de livres et brevets dans le domaine de la m\u00e9decine et de la biologie vasculaires avec plus de 20 000 citations ; h index = 76 (ISI Web of Knowledge, 6-2-13). Il si\u00e8ge \u00e0 des comit\u00e9s nationaux et internationaux qui traitent des maladies cardiovasculaires, notamment l&#039;American Heart Association, l&#039;American College of Cardiology, la Society for Vascular Medicine et le National Heart, Lung and Blood Institute. Il a \u00e9t\u00e9 pr\u00e9sident de la Society for Vascular Medicine, directeur de l&#039;American Board of Vascular Medicine et r\u00e9dacteur en chef adjoint de Vascular Medicine.<\/p>\n<p>Le programme de recherche translationnelle du Dr Cooke est ax\u00e9 sur la r\u00e9g\u00e9n\u00e9ration vasculaire. Le programme est financ\u00e9 par des subventions des National Institutes of Health, de l&#039;American Heart Association et de l&#039;industrie.<\/p>\n<p>Le programme de recherche du Dr Cooke porte sur la restauration ou la stimulation des fonctions endoth\u00e9liales telles que la vasodilatation et l&#039;angiogen\u00e8se, \u00e0 l&#039;aide de petites mol\u00e9cules ou de th\u00e9rapies \u00e0 base de cellules souches. Au cours de ses 25 ann\u00e9es de biologie endoth\u00e9liale translationnelle, il a d&#039;abord d\u00e9crit et caract\u00e9ris\u00e9 les effets anti-ath\u00e9rog\u00e8nes de l&#039;oxyde nitrique d\u00e9riv\u00e9 de l&#039;endoth\u00e9lium; l&#039;effet anti-angiog\u00e9nique de l&#039;inhibiteur de la synthase NO ADMA; la voie angiog\u00e9nique m\u00e9di\u00e9e par les r\u00e9cepteurs endoth\u00e9liaux de l&#039;ac\u00e9tylcholine nicotinique; le r\u00f4le de cette voie dans les \u00e9tats d&#039;angiogen\u00e8se pathologique; et a d\u00e9velopp\u00e9 un antagoniste de la voie qui fait actuellement l&#039;objet d&#039;essais cliniques de phase II. Son groupe de recherche clinique a explor\u00e9 l&#039;utilisation d&#039;agents angiog\u00e9niques et de cellules souches adultes dans le traitement de la maladie art\u00e9rielle p\u00e9riph\u00e9rique. Plus r\u00e9cemment, il a g\u00e9n\u00e9r\u00e9 et caract\u00e9ris\u00e9 des cellules endoth\u00e9liales d\u00e9riv\u00e9es de cellules souches inflammatoires humaines et explor\u00e9 leur r\u00f4le dans l&#039;angiogen\u00e8se et la r\u00e9g\u00e9n\u00e9ration vasculaire. Des d\u00e9couvertes r\u00e9centes du laboratoire ont clarifi\u00e9 le r\u00f4le de la signalisation immunitaire inn\u00e9e dans la reprogrammation nucl\u00e9aire vers la pluripotence et la transdiff\u00e9renciation th\u00e9rapeutique pour les maladies vasculaires.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2015-5\u2033 module_id=\u201d2015-5\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<b>Juin 2015 (date de d\u00e9but 1er septembre 2015) :\u00a0<\/b>\u00c0 Francis S. Collins, MD, PhD, directeur des National Institutes of Health (NIH\/NHGRI), Bethesda, MD ; \u00ab Financement des candidats postdoctoraux pour la recherche HGPS. \u00bb<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Collins%2C-Francis(1).jpg\" width=\"125\" height=\"158\" \/>Le Dr Collins supervise les travaux du plus grand soutien mondial \u00e0 la recherche biom\u00e9dicale, de la recherche fondamentale \u00e0 la recherche clinique. Le Dr Collins et son \u00e9quipe, en collaboration avec la Progeria Research Foundation, ont cod\u00e9couvert la cause g\u00e9n\u00e9tique du HGPS en 2003, et apr\u00e8s plus d&#039;une douzaine d&#039;ann\u00e9es consacr\u00e9es \u00e0 ce travail, leur objectif demeure : comprendre la pathog\u00e9n\u00e8se et trouver des traitements pour le HGPS. Les \u00e9tudes actuelles se concentrent sur des approches th\u00e9rapeutiques potentielles, notamment des m\u00e9thodes bas\u00e9es sur l&#039;ARN et l&#039;utilisation de la rapamycine et de ses analogues, en utilisant \u00e0 la fois des mod\u00e8les cellulaires et murins HGPS.<b><\/b><\/p>\n<p>Francis S. Collins, docteur en m\u00e9decine et titulaire d&#039;un doctorat, est le directeur des National Institutes of Health (NIH). \u00c0 ce titre, il supervise les travaux du plus grand promoteur de la recherche biom\u00e9dicale au monde, couvrant l&#039;ensemble des domaines allant de la recherche fondamentale \u00e0 la recherche clinique.<\/p>\n<p>Le Dr Collins est un m\u00e9decin g\u00e9n\u00e9ticien r\u00e9put\u00e9 pour ses d\u00e9couvertes marquantes sur les g\u00e8nes responsables des maladies et pour son r\u00f4le de chef de file dans le projet international du g\u00e9nome humain, qui a abouti en avril 2003 \u00e0 l&#039;ach\u00e8vement d&#039;un manuel d&#039;instructions sur la s\u00e9quence compl\u00e8te de l&#039;ADN humain. Il a \u00e9t\u00e9 directeur du National Human Genome Research Institute du NIH de 1993 \u00e0 2008.<\/p>\n<p>Le laboratoire de recherche du Dr Collins a d\u00e9couvert un certain nombre de g\u00e8nes importants, notamment ceux responsables de la fibrose kystique, de la neurofibromatose, de la maladie de Huntington, d&#039;un syndrome de cancer endocrinien familial et, plus r\u00e9cemment, des g\u00e8nes du diab\u00e8te de type 2 et du g\u00e8ne responsable du syndrome de prog\u00e9ria de Hutchinson-Gilford, une maladie rare qui provoque un vieillissement pr\u00e9matur\u00e9.<\/p>\n<p>Le Dr Collins a obtenu une licence en chimie de l&#039;Universit\u00e9 de Virginie, un doctorat en chimie physique de l&#039;Universit\u00e9 Yale et un doctorat en m\u00e9decine avec mention de l&#039;Universit\u00e9 de Caroline du Nord \u00e0 Chapel Hill. Avant de rejoindre le NIH en 1993, il a pass\u00e9 neuf ans \u00e0 la facult\u00e9 de l&#039;Universit\u00e9 du Michigan, o\u00f9 il a \u00e9t\u00e9 chercheur au Howard Hughes Medical Institute. Il est membre \u00e9lu de l&#039;Institute of Medicine et de la National Academy of Sciences. Le Dr Collins a re\u00e7u la Presidential Medal of Freedom en novembre 2007 et la National Medal of Science en 2009.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2015-6\u2033 module_id=\u201d2015-6\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<b>Juin 2015 (1er septembre 2015) :\u00a0<\/b>\u00c0 Dudley Lamming, Ph. D., professeur adjoint au d\u00e9partement de m\u00e9decine de l\u2019universit\u00e9 du Wisconsin-Madison, codirecteur de la plateforme de ph\u00e9notypage m\u00e9tabolique de la souris du d\u00e9partement de m\u00e9decine de l\u2019universit\u00e9 du Wisconsin-Madison, Madison, Wisconsin. \u00ab Intervention dans la prog\u00e9ria par restriction d\u2019acides amin\u00e9s alimentaires sp\u00e9cifiques \u00bb<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/LammingDudley.jpg\" width=\"125\" height=\"141\" \/>Le syndrome de Hutchinson-Gilford Progeria (HGPS) est une maladie g\u00e9n\u00e9tique rare et mortelle caract\u00e9ris\u00e9e par un vieillissement rapide. Le traitement des fibroblastes HGPS humains ou des souris d\u00e9pourvues de Lmna (un mod\u00e8le murin de HGPS) avec de la rapamycine, un inhibiteur de la prot\u00e9ine kinase mTOR (cible m\u00e9caniste de la rapamycine), inverse les ph\u00e9notypes HGPS au niveau cellulaire et favorise la dur\u00e9e de vie et la sant\u00e9 au niveau de l&#039;organisme. Cependant, la rapamycine a de graves effets secondaires chez l&#039;homme, notamment une immunosuppression et des effets m\u00e9taboliques diab\u00e9tog\u00e8nes, qui peuvent emp\u00eacher son utilisation \u00e0 long terme chez les patients atteints de HGPS. La prot\u00e9ine kinase mTOR se trouve dans deux complexes distincts, et les travaux de l&#039;\u00e9quipe de recherche du Dr Lamming et ceux de nombreux autres laboratoires sugg\u00e8rent que de nombreux avantages de la rapamycine d\u00e9coulent de la suppression du complexe mTOR 1 (mTORC1), tandis que de nombreux effets secondaires sont dus \u00e0 une inhibition \u00ab hors cible \u00bb du complexe mTOR 2 (mTORC2).<\/p>\n<p>Alors que la rapamycine inhibe les deux complexes mTOR in vivo, mTORC1 et mTORC2 r\u00e9agissent naturellement \u00e0 diff\u00e9rents signaux environnementaux et nutritionnels. mTORC1 est directement stimul\u00e9 par les acides amin\u00e9s, tandis que mTORC2 est principalement r\u00e9gul\u00e9 par l&#039;insuline et la signalisation des facteurs de croissance. L&#039;\u00e9quipe de recherche du Dr Lamming a d\u00e9termin\u00e9 qu&#039;un r\u00e9gime pauvre en prot\u00e9ines r\u00e9duit consid\u00e9rablement la signalisation mTORC1, mais pas mTORC2, dans les tissus de souris. Cela soul\u00e8ve la possibilit\u00e9 intrigante qu&#039;un r\u00e9gime pauvre en prot\u00e9ines puisse \u00eatre une m\u00e9thode relativement simple et \u00e0 faibles effets secondaires pour restreindre l&#039;activit\u00e9 de mTORC1 et apporter un b\u00e9n\u00e9fice th\u00e9rapeutique aux patients atteints de HGPS. Dans cette \u00e9tude, ils identifieront un r\u00e9gime qui inhibe la signalisation mTORC1 in vivo et d\u00e9termineront la capacit\u00e9 de ce r\u00e9gime \u00e0 sauver la pathologie HGPS \u00e0 la fois in vivo dans un mod\u00e8le murin exprimant la prog\u00e9rine de HGPS et in vitro dans des lign\u00e9es cellulaires de patients humains atteints de HGPS.<\/p>\n<p>Dudley Lamming a obtenu son doctorat en pathologie exp\u00e9rimentale \u00e0 l&#039;Universit\u00e9 Harvard en 2008 dans le laboratoire du Dr David Sinclair, et a ensuite suivi une formation postdoctorale au Whitehead Institute for Biomedical Research \u00e0 Cambridge, MA dans le laboratoire du Dr David Sabatini. Les recherches du Dr Lamming sont financ\u00e9es en partie par un prix NIH\/NIA K99\/R00 Pathway to Independence ainsi que par un prix de recherche pour les jeunes professeurs de l&#039;American Federation for Aging Research. Son laboratoire \u00e0 l&#039;Universit\u00e9 du Wisconsin se concentre sur l&#039;\u00e9tude de la mani\u00e8re dont les voies de signalisation sensibles aux nutriments peuvent \u00eatre exploit\u00e9es pour promouvoir la sant\u00e9 et retarder \u00e0 la fois le vieillissement normal et les maladies du vieillissement pr\u00e9matur\u00e9 telles que le syndrome de Hutchinson-Gilford Progeria.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2015-7\u2033 module_id=\u201d2015-7\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<b>Juin 2015 (date de d\u00e9but 1er septembre 2015) :\u00a0<\/b>\u00c0 Cl\u00e1udia Cavadas, PhD, Centre de neurosciences et de biologie cellulaire (CNC), Universit\u00e9 de Coimbra, Coimbra Portugal ; &quot;Le NPY p\u00e9riph\u00e9rique inverse le ph\u00e9notype HGPS\u00a0: une \u00e9tude sur des fibroblastes humains et un mod\u00e8le de souris.&quot;<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Cavadas%2C-Claudia-(1).jpg\" width=\"125\" height=\"137\" \/>Le syndrome de Hutchinson-Gilford progeria (HGPS) est une maladie g\u00e9n\u00e9tique extr\u00eamement rare caract\u00e9ris\u00e9e par un vieillissement pr\u00e9matur\u00e9 et acc\u00e9l\u00e9r\u00e9 et une mort pr\u00e9matur\u00e9e. La d\u00e9couverte de nouveaux compos\u00e9s th\u00e9rapeutiques est de la plus haute importance pour cette maladie mortelle. La mol\u00e9cule endog\u00e8ne neuropeptide Y (NPY) active les r\u00e9cepteurs NPY localis\u00e9s dans divers organes et cellules affect\u00e9s par le HGPS. Nos donn\u00e9es pr\u00e9liminaires et nos publications r\u00e9centes sugg\u00e8rent fortement que le syst\u00e8me neuropeptide Y (NPY) pourrait \u00eatre une cible th\u00e9rapeutique putative pour le HGPS.<\/p>\n<p>Dans cette \u00e9tude, nous allons \u00e9tudier les effets b\u00e9n\u00e9fiques du NPY et\/ou des activateurs des r\u00e9cepteurs du NPY dans le sauvetage du ph\u00e9notype de vieillissement dans deux mod\u00e8les de HGPS : dans un mod\u00e8le cellulaire et dans un mod\u00e8le murin de HGPS. Avec ce projet, nous esp\u00e9rons montrer que l&#039;activation du syst\u00e8me NPY est une strat\u00e9gie innovante pour la th\u00e9rapeutique, ou la co-th\u00e9rapie, du HGPS.<\/p>\n<p>Cl\u00e1udia Cavadas est titulaire d&#039;un doctorat en pharmacologie de la Facult\u00e9 de pharmacie de l&#039;Universit\u00e9 de Coimbra. Elle est chef du groupe \u00ab Neuroendocrinologie et vieillissement \u00bb au CNC - Centre de neurosciences et de biologie cellulaire de l&#039;Universit\u00e9 de Coimbra. Cl\u00e1udia Cavadas est co-auteur de 50 publications et \u00e9tudie le syst\u00e8me du neuropeptide Y (NPY) depuis 1998. Elle est vice-pr\u00e9sidente de la Soci\u00e9t\u00e9 portugaise de pharmacologie (depuis 2013) ; Cl\u00e1udia Cavadas a \u00e9t\u00e9 l&#039;ancienne directrice de l&#039;Institut de recherche interdisciplinaire de l&#039;Universit\u00e9 de Coimbra (2010-2012).<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2014-1\u2033 module_id=\u201d2014-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<b>D\u00e9cembre 2014 (date de d\u00e9but 1er avril 2015) :\u00a0<\/b>\u00c0 C\u00e9lia Alexandra Ferreira de Oliveira Aveleira, PhD, Centre de neurosciences et de biologie cellulaire (CNC) et Institut de recherche interdisciplinaire (IIIUC), Universit\u00e9 de Coimbra Portugal ; &quot;Ghr\u00e9line\u00a0: une nouvelle intervention th\u00e9rapeutique pour sauver le ph\u00e9notype du syndrome de Hutchinson\u2010Gilford Progeria&quot;<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Celia-Aveleira-pic.jpg\" width=\"125\" height=\"174\" \/>Le syndrome de Hutchinson-Gilford progeria (HGPS), une maladie g\u00e9n\u00e9tique mortelle, est caract\u00e9ris\u00e9 par un vieillissement pr\u00e9matur\u00e9 acc\u00e9l\u00e9r\u00e9. Le HGPS est le plus souvent caus\u00e9 par une mutation ponctuelle de novo (G608G) dans le g\u00e8ne de la lamine A\/C (LMNA), produisant une prot\u00e9ine anormale de la lamine A appel\u00e9e prog\u00e9rine. L&#039;accumulation de prog\u00e9rine provoque des anomalies nucl\u00e9aires et un arr\u00eat du cycle cellulaire, conduisant finalement \u00e0 la s\u00e9nescence cellulaire, et constitue donc l&#039;un des m\u00e9canismes sous-jacents \u00e0 la progression du HGPS. Il a \u00e9t\u00e9 d\u00e9montr\u00e9 que la rapamycine, en stimulant l&#039;autophagie, favorise l&#039;\u00e9limination de la prog\u00e9rine et a des effets b\u00e9n\u00e9fiques sur les mod\u00e8les de HGPS. \u00c9tant donn\u00e9 que la rapamycine a des effets ind\u00e9sirables bien connus, l&#039;identification de stimulateurs d&#039;autophagie plus s\u00fbrs, avec d&#039;autres effets b\u00e9n\u00e9fiques, pour le traitement chronique des patients atteints de HGPS est de la plus haute importance.<\/p>\n<p>La ghr\u00e9line est une hormone peptidique circulante et est le ligand endog\u00e8ne du r\u00e9cepteur s\u00e9cr\u00e9tagogue de l&#039;hormone de croissance, ayant donc une activit\u00e9 de lib\u00e9ration de l&#039;hormone de croissance. Outre son effet orexig\u00e8ne bien connu, la ghr\u00e9line a des r\u00f4les b\u00e9n\u00e9fiques dans diff\u00e9rents organes et syst\u00e8mes, tels que l&#039;effet protecteur cardiovasculaire, la r\u00e9gulation de l&#039;ath\u00e9roscl\u00e9rose, la protection contre les l\u00e9sions d&#039;isch\u00e9mie\/reperfusion ainsi que l&#039;am\u00e9lioration du pronostic de l&#039;infarctus du myocarde et de l&#039;insuffisance cardiaque. De plus, la ghr\u00e9line et les analogues de la ghr\u00e9line ont \u00e9t\u00e9 test\u00e9s dans certains essais cliniques pour le traitement de maladies telles que la cachexie dans l&#039;insuffisance cardiaque chronique, la fragilit\u00e9 chez les personnes \u00e2g\u00e9es et les troubles li\u00e9s au d\u00e9ficit en hormone de croissance, et peuvent donc \u00eatre consid\u00e9r\u00e9s comme une strat\u00e9gie th\u00e9rapeutique s\u00fbre. De plus, nos donn\u00e9es tr\u00e8s r\u00e9centes montrent que la ghr\u00e9line stimule l&#039;autophagie et favorise la clairance de la prog\u00e9rine dans les cellules HGPS. Dans cette \u00e9tude, nous \u00e9tudierons le potentiel de la ghr\u00e9line et de l&#039;agoniste du r\u00e9cepteur de la ghr\u00e9line comme traitement du HGPS. \u00c0 cette fin, nous \u00e9valuerons si l&#039;administration p\u00e9riph\u00e9rique de ghr\u00e9line\/agoniste du r\u00e9cepteur de la ghr\u00e9line peut am\u00e9liorer le ph\u00e9notype HGPS et augmenter la dur\u00e9e de vie, en utilisant les souris LmnaG609G\/G609G, un mod\u00e8le de souris HGPS. De plus, nous d\u00e9terminerons \u00e9galement si la ghr\u00e9line inverse le ph\u00e9notype cellulaire s\u00e9nescent HGPS en favorisant l&#039;\u00e9limination de la prog\u00e9rine par l&#039;autophagie, un m\u00e9canisme par lequel les cellules \u00e9liminent les prot\u00e9ines et organites inutiles ou dysfonctionnels pour maintenir l&#039;hom\u00e9ostasie cellulaire.<\/p>\n<p>C\u00e9lia Aveleira a obtenu son doctorat en sciences biom\u00e9dicales \u00e0 l&#039;Universit\u00e9 de Coimbra, au Portugal, en 2010. Elle a r\u00e9alis\u00e9 sa th\u00e8se au Centre d&#039;ophtalmologie et des sciences de la vision, Facult\u00e9 de m\u00e9decine, Universit\u00e9 de Coimbra, Portugal et au D\u00e9partement de physiologie cellulaire et mol\u00e9culaire, Penn State College of Medicine, Penn State University, Hershey, Pennsylvanie, \u00c9tats-Unis. Apr\u00e8s cela, elle a rejoint le groupe de recherche de Cl\u00e1udia Cavadas au Centre de neurosciences et de biologie cellulaire, Universit\u00e9 de Coimbra, Portugal, pour mener ses \u00e9tudes postdoctorales. Elle a obtenu une bourse postdoctorale FCT pour \u00e9tudier le r\u00f4le potentiel du neuropeptide Y (NPY) comme mim\u00e9tique de la restriction calorique pour r\u00e9duire le vieillissement et am\u00e9liorer les maladies li\u00e9es \u00e0 l&#039;\u00e2ge. En 2013, elle a pris son poste actuel au CNC, en tant que chercheuse scientifique invit\u00e9e. Ses recherches portent sur le r\u00f4le des mim\u00e9tiques de restriction calorique comme cibles th\u00e9rapeutiques pour retarder le processus de vieillissement des maladies de vieillissement normales et pr\u00e9matur\u00e9es, telles que le syndrome de prog\u00e9ria de Hutchinson-Gilford (HGPS), avec un accent particulier sur les m\u00e9canismes hom\u00e9ostatiques, tels que l&#039;autophagie et la capacit\u00e9 de r\u00e9g\u00e9n\u00e9ration tissulaire des cellules souches\/prog\u00e9nitrices.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2014-2\u2033 module_id=\u201d2014-2\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2014 (date de d\u00e9but 1er f\u00e9vrier 2015) :\u00a0<\/strong>\u00c0 Jes\u00fas V\u00e1zquez Cobos, PhD, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Espagne ; \u00ab Quantification de la prog\u00e9rine farn\u00e9syl\u00e9e dans les tissus de souris prog\u00e9ro\u00efdes et les leucocytes circulants des patients atteints de prog\u00e9ria Hutchinson-Gilford \u00bb<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/jvazquezpic.jpg\" width=\"125\" height=\"166\" \/>Le syndrome de Hutchinson-Gilford progeria (HGPS) est une maladie rare caract\u00e9ris\u00e9e par un vieillissement pr\u00e9matur\u00e9 s\u00e9v\u00e8re et la mort (\u00e2ge m\u00e9dian de 13,4 ans). De loin, la cause la plus fr\u00e9quente du HGPS est une mutation du g\u00e8ne codant pour la prot\u00e9ine lamine A qui entra\u00eene l&#039;accumulation de prog\u00e9rine, une forme modifi\u00e9e de la lamine A qui contient une modification chimique appel\u00e9e farn\u00e9sylation et qui est cens\u00e9e produire la pathologie. Par cons\u00e9quent, les scientifiques tentent de d\u00e9velopper des th\u00e9rapies qui emp\u00eachent cette modification. Cependant, l&#039;analyse des r\u00e9sultats de ces th\u00e9rapies exp\u00e9rimentales est difficile car \u00e0 ce jour, il n&#039;existe aucune m\u00e9thode fiable pour mesurer les niveaux de prog\u00e9rine farn\u00e9syl\u00e9e dans des mod\u00e8les animaux ou chez des patients atteints de HGPS. Les chercheurs du CNIC ont d\u00e9montr\u00e9 que les niveaux de la prot\u00e9ine modifi\u00e9e peuvent \u00eatre quantifi\u00e9s de mani\u00e8re fiable dans des fibroblastes cultiv\u00e9s (une pr\u00e9paration de cellules obtenues \u00e0 partir de la peau) de souris et \u00e9galement de HGPS en utilisant une technique appel\u00e9e spectrom\u00e9trie de masse. Dans le cadre du projet actuel, les chercheurs tentent d\u2019am\u00e9liorer la technique pour pouvoir quantifier la prog\u00e9rine farn\u00e9syl\u00e9e directement dans les \u00e9chantillons de sang des patients atteints de HGPS. Si cette technique r\u00e9ussit, les scientifiques disposeront d\u2019un outil pr\u00e9cieux pour \u00e9valuer l\u2019efficacit\u00e9 des traitements exp\u00e9rimentaux chez l\u2019homme et pour surveiller la progression et la gravit\u00e9 de cette maladie.<\/p>\n<p>Fran\u00e7ais Le Dr Jes\u00fas V\u00e1zquez est dipl\u00f4m\u00e9 en chimie physique de l&#039;Universit\u00e9 Complutense (Madrid, 1982) et a r\u00e9alis\u00e9 son doctorat en biochimie \u00e0 l&#039;Universit\u00e9 autonome (Madrid, 1986), tous deux avec distinction sp\u00e9ciale. Au cours de sa formation postdoctorale aux laboratoires de recherche Merck Sharp (NJ, \u00c9tats-Unis) et au Centro de Biolog\u00eda Molecular Severo Ochoa (Madrid), il s&#039;est sp\u00e9cialis\u00e9 en chimie des prot\u00e9ines et dans l&#039;\u00e9tude des biomembranes dans le contexte des maladies neurochimiques. Depuis lors, il a jou\u00e9 un r\u00f4le pionnier dans le d\u00e9veloppement de la chimie des prot\u00e9ines, de la spectrom\u00e9trie de masse et de la prot\u00e9omique en Espagne. Son laboratoire a apport\u00e9 des contributions importantes au domaine en abordant des sujets tels que les m\u00e9canismes de fragmentation des peptides, le s\u00e9quen\u00e7age de novo des peptides et l&#039;analyse des modifications post-traductionnelles. Au cours des derni\u00e8res ann\u00e9es, il a consacr\u00e9 un effort consid\u00e9rable au d\u00e9veloppement de techniques de deuxi\u00e8me g\u00e9n\u00e9ration, \u00e0 la quantification relative du prot\u00e9ome par marquage isotopique stable, \u00e0 des algorithmes avanc\u00e9s pour l&#039;int\u00e9gration de donn\u00e9es quantitatives et la biologie des syst\u00e8mes, et \u00e0 la caract\u00e9risation \u00e0 haut d\u00e9bit des modifications produites par le stress oxydatif. Ces techniques ont \u00e9t\u00e9 appliqu\u00e9es \u00e0 plusieurs projets de recherche, o\u00f9 il \u00e9tudie les m\u00e9canismes mol\u00e9culaires sous-jacents \u00e0 des processus tels que l&#039;angiogen\u00e8se et le stress nitroxydatif dans l&#039;endoth\u00e9lium, l&#039;isch\u00e9mie-pr\u00e9conditionnement dans les cardiomyocytes et les mitochondries et l&#039;interactome dans la synapse immunitaire et dans les exosomes. Auteur de plus d&#039;une centaine de publications internationales, il est professeur de recherche au CSIC et directeur de la plateforme de prot\u00e9omique du RIC (r\u00e9seau espagnol de recherche cardiovasculaire). Il a rejoint le CNIC en tant que professeur titulaire en 2011, o\u00f9 il dirige le laboratoire de prot\u00e9omique cardiovasculaire et est \u00e9galement responsable de l&#039;unit\u00e9 de prot\u00e9omique.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2014-3\u2033 module_id=\u201d2014-3\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<b>D\u00e9cembre 2014 (<strong>date de d\u00e9but 1er f\u00e9vrier 2015<\/strong>):\u00a0<\/b>\u00c0 Marsha Moses, PhD, Boston Children&#039;s Hospital, Boston, MA ; \u00ab D\u00e9couverte de nouveaux biomarqueurs non invasifs pour le syndrome de Hutchinson-Gilford prog\u00e9ria \u00bb<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Moses.jpg\" width=\"125\" height=\"186\" \/>Notre objectif est d&#039;am\u00e9liorer notre compr\u00e9hension collective du d\u00e9veloppement et de la progression des maladies gr\u00e2ce \u00e0 l&#039;identification de biomarqueurs, dans le but de faire progresser le traitement actuel et de d\u00e9velopper et d&#039;\u00e9valuer de nouvelles th\u00e9rapies pour le syndrome de Hutchinson-Gilford Progeria (HGPS) et potentiellement pour les maladies cardiovasculaires (MCV) dans la population g\u00e9n\u00e9rale.\u00a0<i>Non\u00a0<\/i>capacit\u00e9 constante \u00e0 d\u00e9terminer qui pr\u00e9sente un risque de progression ou qui r\u00e9pondra au traitement. Des tests pr\u00e9cis, bas\u00e9s sur un marqueur ou un panel de marqueurs sp\u00e9cifiques et d\u00e9finissables, sont essentiels pour normaliser les directives cliniques, le diagnostic et la prise en charge. Nous avons l&#039;intention d&#039;utiliser une approche de d\u00e9couverte prot\u00e9omique de pointe pour atteindre notre objectif de d\u00e9couverte et de validation de biomarqueurs minimalement invasifs du HGPS et potentiellement du vieillissement et des maladies cardiovasculaires. Les connaissances acquises dans ces \u00e9tudes sur le HGPS \u00e9claireront et \u00e9largiront consid\u00e9rablement nos connaissances sur les m\u00e9canismes sous-jacents au HGPS. Il existe \u00e9galement un fort potentiel que les d\u00e9couvertes de biomarqueurs r\u00e9alis\u00e9es dans ces \u00e9tudes puissent finalement repr\u00e9senter des cibles th\u00e9rapeutiques potentielles pour le HGPS, les maladies cardiovasculaires et d&#039;autres troubles li\u00e9s au vieillissement.<\/p>\n<p>Le Dr Marsha A. Moses est professeur Julia Dyckman Andrus \u00e0 la Harvard Medical School et directrice du programme de biologie vasculaire au Boston Children&#039;s Hospital. Elle s&#039;int\u00e9resse depuis longtemps \u00e0 l&#039;identification et \u00e0 la caract\u00e9risation des m\u00e9canismes biochimiques et mol\u00e9culaires qui sous-tendent la r\u00e9gulation de la croissance et de la progression tumorales. Le Dr Moses et son laboratoire ont d\u00e9couvert un certain nombre d&#039;inhibiteurs de l&#039;angiogen\u00e8se qui fonctionnent \u00e0 la fois au niveau transcriptionnel et translationnel, dont certains sont en cours de tests pr\u00e9cliniques. Nomm\u00e9e pionni\u00e8re dans le domaine passionnant de la m\u00e9decine des biomarqueurs par le\u00a0<i>Journal de l&#039;Institut national du cancer<\/i>Le Dr Moses a mis en place une initiative de prot\u00e9omique dans son laboratoire qui a conduit \u00e0 la d\u00e9couverte de panels de biomarqueurs urinaires non invasifs du cancer qui peuvent pr\u00e9dire l&#039;\u00e9tat et le stade de la maladie chez les patients atteints de cancer et qui sont des marqueurs sensibles et pr\u00e9cis de la progression de la maladie et de l&#039;efficacit\u00e9 th\u00e9rapeutique des m\u00e9dicaments contre le cancer. Un certain nombre de ces tests urinaires ont \u00e9t\u00e9 commercialis\u00e9s. Ces diagnostics et th\u00e9rapies sont inclus dans l&#039;important portefeuille de brevets du Dr Moses, compos\u00e9 de brevets am\u00e9ricains et \u00e9trangers.<\/p>\n<p>Les travaux fondamentaux et translationnels du Dr Moses ont \u00e9t\u00e9 publi\u00e9s dans des revues telles que\u00a0<i>Science<\/i>, le\u00a0<i>Journal de m\u00e9decine de la Nouvelle-Angleterre<\/i>,\u00a0<i>Cellule<\/i>\u00a0et le\u00a0<i>Journal de chimie biologique<\/i>, entre autres. Le Dr Moses a obtenu un doctorat en biochimie de l&#039;Universit\u00e9 de Boston et a effectu\u00e9 une bourse postdoctorale des National Institutes of Health au Boston Children&#039;s Hospital et au MIT. Elle a re\u00e7u un certain nombre de subventions et de prix du NIH et de fondations. Le Dr Moses a re\u00e7u les deux prix de mentorat de la Harvard Medical School, le A. Clifford Barger Mentoring Award (2003) et le Joseph B. Martin Dean&#039;s Leadership Award for the Advancement of Women Faculty (2009). En 2013, elle a re\u00e7u le prix de membre honoraire de l&#039;Association of Women Surgeons de l&#039;American College of Surgeons. Le Dr Moses a \u00e9t\u00e9 \u00e9lue au\u00a0<i>Institut de m\u00e9decine<\/i>\u00a0de la\u00a0<i>Acad\u00e9mies nationales des \u00c9tats-Unis<\/i>\u00a0en 2008 et \u00e0 la\u00a0<i>Acad\u00e9mie nationale des inventeurs<\/i>\u00a0en 2013.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2014-4\u2033 module_id=\u201d2014-4\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2014 (date de d\u00e9but 1er mars 2015) :\u00a0<\/strong>\u00c0 Joseph Rabinowitz, PhD, Temple University School of Medicine, Philadelphie, PA ; \u00ab Co-administration m\u00e9di\u00e9e par un virus ad\u00e9no-associ\u00e9 de lamine A de type sauvage et de microARN contre la prog\u00e9rine \u00bb<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/JRabinowitz-pic.jpg\" width=\"125\" height=\"187\" \/>Le virus ad\u00e9no-associ\u00e9 (AAV) est un petit virus \u00e0 ADN non pathog\u00e8ne qui est utilis\u00e9 pour administrer des g\u00e8nes non viraux et d&#039;autres ADN th\u00e9rapeutiques aux animaux et \u00e0 l&#039;homme. L&#039;int\u00e9gralit\u00e9 du g\u00e9nome viral, \u00e0 l&#039;exception de 145 bases \u00e0 chaque extr\u00e9mit\u00e9, peut \u00eatre retir\u00e9e de sorte qu&#039;aucun g\u00e8ne viral ne soit inclus dans l&#039;ADN qui est emball\u00e9 dans l&#039;enveloppe du virus (virion). Les microARN (miR) sont de petits morceaux d&#039;ARN qui r\u00e9duisent l&#039;expression des prot\u00e9ines en interf\u00e9rant avec l&#039;ARN messager correspondant de cette ou ces prot\u00e9ines. La recherche a d\u00e9montr\u00e9 que la lamine A (LMNA) n&#039;est pas exprim\u00e9e \u00e0 des niveaux \u00e9lev\u00e9s dans le cerveau, et que l&#039;expression de miR-9 dans le cerveau est responsable de cette suppression. Nous allons emballer miR-9 dans un g\u00e9nome AAV et examiner le niveau de suppression de LMNA dans les lign\u00e9es cellulaires humaines de prog\u00e9ria et de non-prog\u00e9ria du m\u00eame \u00e2ge. De plus, nous emballerons miR-9 et LMNA (qui ne peuvent pas \u00eatre supprim\u00e9s par miR-9) dans AAV et examinerons les cellules pour sauver le ph\u00e9notype de prog\u00e9ria. Si ces \u00e9tapes sont fructueuses, nous les r\u00e9p\u00e9terons sur un mod\u00e8le murin de Progeria.<\/p>\n<p>Joseph Rabinowitz, PhD, est professeur adjoint de pharmacologie au Centre de m\u00e9decine translationnelle de la facult\u00e9 de m\u00e9decine de l&#039;universit\u00e9 Temple \u00e0 Philadelphie, en Pennsylvanie. Le Dr Rabinowitz a obtenu son doctorat en g\u00e9n\u00e9tique \u00e0 la Case Western Reserve University \u00e0 Cleveland, Ohio (professeur Terry Magnuson, PhD). Il a effectu\u00e9 ses \u00e9tudes postdoctorales \u00e0 l&#039;universit\u00e9 de Caroline du Nord \u00e0 Chapel Hill, au centre de th\u00e9rapie g\u00e9nique (R. Jude Samulski, directeur), o\u00f9 il a commenc\u00e9 \u00e0 travailler avec le virus ad\u00e9no-associ\u00e9 comme v\u00e9hicule de th\u00e9rapie g\u00e9nique. En 2004, il a rejoint la facult\u00e9 de l&#039;universit\u00e9 Thomas Jefferson. Son laboratoire s&#039;est concentr\u00e9 sur le d\u00e9veloppement de s\u00e9rotypes de virus ad\u00e9no-associ\u00e9s comme v\u00e9hicules de transfert de g\u00e8nes vers le c\u0153ur. En 2012, il a rejoint la facult\u00e9 de m\u00e9decine de l&#039;universit\u00e9 Temple et est directeur du noyau de vecteurs viraux. Les virus peuvent \u00eatre utilis\u00e9s comme outils pour d\u00e9livrer des g\u00e8nes th\u00e9rapeutiques \u00e0 des animaux de laboratoire et dans des essais cliniques sur des humains.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2014-5\u2033 module_id=\u201d2014-5\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Juillet 2014 (date de d\u00e9but 1er novembre 2014) :\u00a0<\/strong>\u00c0 Vicente Andr\u00e9s Garc\u00eda, PhD, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Espagne ; \u00ab\u00a0G\u00e9n\u00e9ration d&#039;un mod\u00e8le porcin knock-in HGPS pour acc\u00e9l\u00e9rer le d\u00e9veloppement d&#039;applications cliniques efficaces\u00a0\u00bb.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/V_Andres.jpg\" width=\"125\" height=\"158\" \/>Chercheur principal : Vicente Andr\u00e9s, PhD, Laboratoire de physiopathologie cardiovasculaire mol\u00e9culaire et g\u00e9n\u00e9tique, D\u00e9partement d&#039;\u00e9pid\u00e9miologie, d&#039;ath\u00e9rothrombose et d&#039;imagerie, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Espagne.<\/p>\n<p>Le syndrome de prog\u00e9ria de Hutchinson-Gilford (HGPS) est caus\u00e9 par des mutations dans\u00a0<i>LMNA<\/i>\u00a0g\u00e8ne qui conduit \u00e0 la production de prog\u00e9rine, une prot\u00e9ine anormale qui conserve une modification farn\u00e9syle toxique. Les patients atteints de HGPS pr\u00e9sentent une ath\u00e9roscl\u00e9rose g\u00e9n\u00e9ralis\u00e9e et meurent principalement d&#039;un infarctus du myocarde ou d&#039;un accident vasculaire c\u00e9r\u00e9bral \u00e0 un \u00e2ge moyen de 13,4 ans, mais on sait tr\u00e8s peu de choses sur les m\u00e9canismes par lesquels la prog\u00e9rine acc\u00e9l\u00e8re les maladies cardiovasculaires (MCV). Des recherches pr\u00e9cliniques suppl\u00e9mentaires sont donc n\u00e9cessaires pour trouver un rem\u00e8de au HGPS.<\/p>\n<p>Contrairement aux essais sur les maladies courantes, les essais cliniques sur les patients atteints de HGPS seront toujours limit\u00e9s par la petite taille de la cohorte. Il est donc de la plus haute importance de r\u00e9aliser des \u00e9tudes pr\u00e9cliniques sur les mod\u00e8les animaux les plus appropri\u00e9s. De nos jours, les mod\u00e8les de souris g\u00e9n\u00e9tiquement modifi\u00e9es sont la r\u00e9f\u00e9rence absolue pour les \u00e9tudes pr\u00e9cliniques sur le HGPS. Cependant, les souris ne reproduisent pas fid\u00e8lement tous les aspects de la pathologie humaine. Compar\u00e9s aux rongeurs, les porcs ressemblent davantage aux humains en termes de taille du corps et des organes, d&#039;anatomie, de long\u00e9vit\u00e9, de g\u00e9n\u00e9tique et de physiopathologie. Il est remarquable que l&#039;ath\u00e9roscl\u00e9rose chez les porcs reproduise de pr\u00e8s les principales caract\u00e9ristiques morphologiques et biochimiques de la maladie humaine, y compris la forme et la distribution des plaques d&#039;ath\u00e9roscl\u00e9rose, qui s&#039;accumulent principalement dans l&#039;aorte, les art\u00e8res coronaires et les art\u00e8res carotides. Notre objectif principal est de g\u00e9n\u00e9rer et de caract\u00e9riser des porcs g\u00e9n\u00e9tiquement modifi\u00e9s porteurs de la maladie.<i>\u00a0<\/i><i>LMNA<\/i>\u00a0Mutation c.1824C&gt;T, la mutation la plus fr\u00e9quente chez les patients atteints de HGPS. Les recherches utilisant ce grand mod\u00e8le animal devraient permettre des avanc\u00e9es majeures dans nos connaissances fondamentales sur les maladies cardiovasculaires dans la prog\u00e9ria et acc\u00e9l\u00e9rer le d\u00e9veloppement d&#039;applications cliniques efficaces.<\/p>\n<p>Vicente Andr\u00e9s a obtenu son doctorat en sciences biologiques \u00e0 l&#039;Universit\u00e9 de Barcelone (1990). Au cours de sa formation postdoctorale \u00e0 l&#039;h\u00f4pital pour enfants de l&#039;Universit\u00e9 Harvard (1991-1994) et au centre m\u00e9dical St. Elizabeth de l&#039;Universit\u00e9 Tufts (1994-1995), il a men\u00e9 des \u00e9tudes sur le r\u00f4le des facteurs de transcription hom\u00e9obox et MEF2 dans les processus de diff\u00e9renciation et de prolif\u00e9ration cellulaires ; c&#039;est \u00e9galement au cours de cette p\u00e9riode qu&#039;il a d\u00e9velopp\u00e9 un int\u00e9r\u00eat pour la recherche cardiovasculaire. Sa carri\u00e8re de chercheur ind\u00e9pendant a d\u00e9but\u00e9 en 1995 lorsqu&#039;il a \u00e9t\u00e9 nomm\u00e9 professeur adjoint de m\u00e9decine \u00e0 Tufts. Depuis lors, le Dr Andr\u00e9s et son groupe ont \u00e9tudi\u00e9 le remodelage vasculaire au cours de l&#039;ath\u00e9roscl\u00e9rose et de la rest\u00e9nose post-angioplastie, et plus r\u00e9cemment, ils ont \u00e9tudi\u00e9 le r\u00f4le de l&#039;enveloppe nucl\u00e9aire dans la r\u00e9gulation de la transduction du signal, de l&#039;expression g\u00e9n\u00e9tique et de l&#039;activit\u00e9 du cycle cellulaire dans les maladies cardiovasculaires et le vieillissement, en mettant l&#039;accent sur les lamines de type A et le syndrome de prog\u00e9ria de Hutchinson-Gilford (HGPS).<\/p>\n<p>Apr\u00e8s avoir obtenu un poste de chercheur scientifique titulaire au Conseil national de la recherche scientifique (CSIC), le Dr Andr\u00e9s est retourn\u00e9 en Espagne en 1999 pour cr\u00e9er son groupe de recherche \u00e0 l&#039;Institut de biom\u00e9decine de Valence, o\u00f9 il a travaill\u00e9 comme professeur titulaire. Depuis 2006, son groupe est membre du R\u00e9seau th\u00e9matique de recherche coop\u00e9rative sur les maladies cardiovasculaires (RECAVA). Il a rejoint le Centre national de recherche cardiovasculaire (CNIC) en septembre 2009. En 2010, il a re\u00e7u le prix Docteur Leon Dumont de la Soci\u00e9t\u00e9 belge de cardiologie.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2013-1\u2033 module_id=\u201d2013-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Juin 2013 (date de d\u00e9but 1er septembre 2013) :\u00a0<\/strong>Au Dr Brian Snyder, PhD, : Beth Israel Deaconess Medical Center, Boston, MA. ; \u00ab Caract\u00e9risation des ph\u00e9notypes musculo-squelettiques, craniofaciaux et cutan\u00e9s du mod\u00e8le murin de prog\u00e9ria G608G \u00bb.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/snyder_1.jpg\" width=\"144\" height=\"129\" \/><\/p>\n<p>Un mod\u00e8le murin de prog\u00e9ria a \u00e9t\u00e9 d\u00e9velopp\u00e9 au NIH et pr\u00e9sente les m\u00eames caract\u00e9ristiques musculo-squelettiques que celles observ\u00e9es chez les enfants atteints de prog\u00e9ria. \u00c0 ce jour, aucune \u00e9valuation approfondie des caract\u00e9ristiques musculo-squelettiques de la prog\u00e9ria n&#039;a \u00e9t\u00e9 r\u00e9alis\u00e9e dans ce mod\u00e8le animal. En particulier, la question de la raideur articulaire n&#039;a pas non plus \u00e9t\u00e9 \u00e9valu\u00e9e en d\u00e9tail, et il n&#039;est pas clair si cela est la cons\u00e9quence de modifications de la peau, des muscles, de la capsule articulaire, du cartilage articulaire ou d&#039;une d\u00e9formation articulaire.<\/p>\n<p>Nous proc\u00e9derons \u00e0 une \u00e9valuation approfondie de ce mod\u00e8le de souris \u00e0 l&#039;aide de tomodensitom\u00e9tries corporelles compl\u00e8tes du squelette, de la vascularisation et des articulations. Nous r\u00e9aliserons \u00e9galement des \u00e9tudes biom\u00e9caniques des os, du cartilage et de la peau pour caract\u00e9riser les changements (par rapport \u00e0 un animal normal) de forme de l&#039;os, la calcification des vaisseaux sanguins, les changements au niveau du cr\u00e2ne et de la peau.<\/p>\n<p>Nous \u00e9valuerons \u00e9galement dans quelle mesure ces changements ph\u00e9notypiques sont interd\u00e9pendants et si ces changements peuvent \u00eatre utilis\u00e9s pour suivre la gravit\u00e9 de la maladie et la r\u00e9ponse au traitement. Par exemple, les changements dans le syst\u00e8me musculo-squelettique sont-ils pr\u00e9dictifs des changements dans le syst\u00e8me vasculaire ?<\/p>\n<p>Brian D. Snyder, MD, Ph.D., est un chirurgien orthop\u00e9diste p\u00e9diatrique certifi\u00e9 au sein du personnel du Boston Children&#039;s Hospital, o\u00f9 sa pratique clinique se concentre sur la dysplasie de la hanche et les d\u00e9formations acquises de la hanche, les d\u00e9formations de la colonne vert\u00e9brale, la paralysie c\u00e9r\u00e9brale et les traumatismes p\u00e9diatriques. Il est directeur de la clinique de paralysie c\u00e9r\u00e9brale du Boston Children&#039;s Hospital. De plus, il est professeur associ\u00e9 de chirurgie orthop\u00e9dique \u00e0 la Harvard Medical School et directeur associ\u00e9 du Center for Advanced Orthopaedic Studies (CAOS) au Beth Israel Deaconess Medical Center (anciennement le laboratoire de biom\u00e9canique orthop\u00e9dique). Le laboratoire est un centre de recherche multidisciplinaire associ\u00e9 aux d\u00e9partements de bio-ing\u00e9nierie de l&#039;universit\u00e9 de Harvard, du Massachusetts Institute of Technology, de l&#039;universit\u00e9 de Boston, de la Harvard Medical School et du Harvard Combined Orthopaedic Residency Program. Le Dr Snyder a fusionn\u00e9 les techniques d&#039;analyse sophistiqu\u00e9es d\u00e9velopp\u00e9es au laboratoire avec les techniques diagnostiques et chirurgicales innovantes d\u00e9velopp\u00e9es au Children&#039;s Hospital pour le traitement des maladies musculo-squelettiques. Le groupe du Dr Snyder se concentre sur la recherche fondamentale et appliqu\u00e9e en biom\u00e9canique musculosquelettique, notamment : la caract\u00e9risation des relations structure-propri\u00e9t\u00e9 osseuse ; la pr\u00e9vention des fractures pathologiques r\u00e9sultant de maladies osseuses m\u00e9taboliques et du cancer m\u00e9tastatique ; l&#039;analyse biom\u00e9canique des m\u00e9canismes de l\u00e9sion de la colonne vert\u00e9brale et le d\u00e9veloppement de technologies permettant d&#039;\u00e9valuer les propri\u00e9t\u00e9s biochimiques et biom\u00e9caniques du cartilage hyalin dans les articulations synoviales. Le Dr Snyder analysera les changements dans le squelette axial et appendiculaire du mod\u00e8le murin homozygote de la mutation du g\u00e8ne G609G dans le g\u00e8ne LMNA qui conduit au syndrome de Hutchinson-Gilford Progeria (HGPS) en utilisant le logiciel d&#039;analyse de rigidit\u00e9 structurelle bas\u00e9 sur la tomodensitom\u00e9trie que son laboratoire a d\u00e9velopp\u00e9 et valid\u00e9 pour pr\u00e9dire avec pr\u00e9cision le risque de fracture chez les enfants et les adultes atteints de n\u00e9oplasmes osseux b\u00e9nins et malins et mesurer la r\u00e9ponse du squelette appendiculaire au traitement chez les enfants atteints de Progeria.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2013-2\u2033 module_id=\u201d2013-2\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Juin 2013 (date de d\u00e9but 1er septembre 2013) :\u00a0<\/strong>Au Dr Robert Goldman, PhD, : Northwestern University ; \u00ab Nouvelles perspectives sur le r\u00f4le de la prog\u00e9rine en pathologie cellulaire \u00bb.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Goldman-RD-portrait-2007-2010.jpg\" width=\"150\" height=\"219\" \/>Le syndrome de Hutchinson-Gilford Progeria (HGPS) est un trouble de vieillissement pr\u00e9matur\u00e9 segmentaire rare dans lequel les enfants affect\u00e9s acqui\u00e8rent plusieurs caract\u00e9ristiques ph\u00e9notypiques de vieillissement acc\u00e9l\u00e9r\u00e9. La majorit\u00e9 des cas de HGPS sont caus\u00e9s par une mutation de novo dans le g\u00e8ne codant la lamine A (LA) qui active un site d&#039;\u00e9pissage cryptique dans le transcrit primaire. L&#039;ARNm r\u00e9sultant code une LA farn\u00e9syl\u00e9e en permanence avec une d\u00e9l\u00e9tion de 50 acides amin\u00e9s dans le domaine terminal carboxyle appel\u00e9 prog\u00e9rine. Bien qu&#039;il ait \u00e9t\u00e9 d\u00e9montr\u00e9 que cette prog\u00e9rine farn\u00e9syl\u00e9e en permanence est le facteur causal de la maladie, le m\u00e9canisme par lequel la prot\u00e9ine anormale exerce ses effets reste inconnu. R\u00e9cemment, le Dr Goldman et d&#039;autres ont cartographi\u00e9 de nombreux sites de modification post-traductionnelle dans LA. Il a r\u00e9cemment observ\u00e9 que LA contient trois r\u00e9gions distinctes de r\u00e9sidus de s\u00e9rine et de thr\u00e9onine phosphoryl\u00e9s dans ses domaines C- et N-terminaux non structur\u00e9s non h\u00e9lico\u00efdaux alpha. L&#039;une de ces r\u00e9gions se trouve enti\u00e8rement dans le peptide de 50 acides amin\u00e9s supprim\u00e9 dans la prog\u00e9rine, ce qui sugg\u00e8re que cette r\u00e9gion et sa modification post-traductionnelle pourraient \u00eatre impliqu\u00e9es dans le traitement et la fonction de l&#039;AL. Son laboratoire a \u00e9galement identifi\u00e9 plusieurs sites de phosphorylation qui ont un taux de renouvellement \u00e9lev\u00e9 de la phosphorylation pendant l&#039;interphase. Il s&#039;agit notamment des deux principaux sites de phosphorylation dont l&#039;importance pour le d\u00e9sassemblage et l&#039;assemblage de la lamine lors de la mitose a \u00e9t\u00e9 d\u00e9montr\u00e9e. Un autre site \u00e0 taux de renouvellement \u00e9lev\u00e9 est pr\u00e9sent dans la r\u00e9gion proche de l&#039;extr\u00e9mit\u00e9 carboxyle et est supprim\u00e9 dans la prog\u00e9rine. Des exp\u00e9riences pr\u00e9liminaires indiquent que ces sites \u00e0 taux de renouvellement \u00e9lev\u00e9 sont impliqu\u00e9s dans la r\u00e9gulation de la localisation et de la mobilit\u00e9 de l&#039;AL. Le Dr Goldman \u00e9tudiera le r\u00f4le de la phosphorylation sp\u00e9cifique au site dans le traitement, la localisation, la mobilit\u00e9 et l&#039;assemblage de l&#039;AL et de la prog\u00e9rine dans une structure de lamina. Les \u00e9tudes propos\u00e9es pourraient apporter un nouvel \u00e9clairage sur la fonction des modifications post-traductionnelles de sites sp\u00e9cifiques au sein de l&#039;AL, en particulier ceux qui sont supprim\u00e9s dans la prog\u00e9rine. Les r\u00e9sultats devraient fournir de nouvelles perspectives sur l&#039;\u00e9tiologie du HGPS. Les r\u00e9sultats de ces \u00e9tudes pourraient \u00e9galement indiquer de nouvelles interventions th\u00e9rapeutiques pour les patients atteints de HGPS, ciblant les modifications de LA qui sont importantes pour la r\u00e9gulation des fonctions de la lamine.<\/p>\n<p>Robert D. Goldman, Ph. D., est professeur Stephen Walter Ranson et pr\u00e9sident du d\u00e9partement de biologie cellulaire et mol\u00e9culaire \u00e0 la facult\u00e9 de m\u00e9decine Feinberg de l&#039;universit\u00e9 Northwestern. Il est une autorit\u00e9 en mati\u00e8re de structure et de fonction des syst\u00e8mes de filaments interm\u00e9diaires du cytosquelette et du nucl\u00e9osquelette. Lui et ses coll\u00e8gues ont publi\u00e9 plus de 240 articles scientifiques. Ses travaux lui ont valu de nombreuses distinctions et r\u00e9compenses, notamment un prix Ellison Foundation Senior Scholar Award sur le vieillissement humain et un prix MERIT du National Institute of General Medical Sciences. Le Dr Goldman est membre de l&#039;American Association for the Advancement of Science et a si\u00e9g\u00e9 \u00e0 son conseil d&#039;administration de 1997 \u00e0 2001. Il a occup\u00e9 de nombreux postes au sein de la communaut\u00e9 scientifique, notamment l&#039;organisation de r\u00e9unions et la r\u00e9daction de monographies et de manuels de laboratoire pour le Cold Spring Harbor Laboratory et a si\u00e9g\u00e9 \u00e0 des comit\u00e9s d&#039;examen pour l&#039;American Cancer Society et le NIH. Il a \u00e9t\u00e9 pr\u00e9sident de l&#039;American Society for Cell Biology et des pr\u00e9sidents de l&#039;American Association of Anatomy, Cell Biology and Neuroscience. Goldman a fond\u00e9 et dirig\u00e9 pendant de nombreuses ann\u00e9es le programme de bourses d&#039;\u00e9tudes scientifiques pour les r\u00e9dacteurs scientifiques au Marine Biological Laboratory (MBL) et a si\u00e9g\u00e9 au conseil d&#039;administration du MBL, en tant que directeur du cours de physiologie du MBL et directeur du centre de recherche Whitman du MBL. Il est r\u00e9dacteur en chef adjoint du FASEB Journal, de la biologie mol\u00e9culaire de la cellule et de la bioarchitecture. Il fait \u00e9galement partie des comit\u00e9s de r\u00e9daction d&#039;Aging Cell et de Nucleus.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2013-3\u2033 module_id=\u201d2013-3\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Juin 2013 (date de d\u00e9but 1er septembre 2013) :\u00a0<\/strong>Au Dr Christopher Carroll, PhD, : Universit\u00e9 Yale, New Haven, CT ; \u00ab R\u00e9gulation de l&#039;abondance de la prog\u00e9rine par la prot\u00e9ine de la membrane nucl\u00e9aire interne Man1 \u00bb.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Carroll.jpg\" width=\"150\" height=\"176\" \/>Les m\u00e9canismes mol\u00e9culaires qui contr\u00f4lent l&#039;abondance de la prot\u00e9ine Lamine A ne sont pas bien compris. Nous avons montr\u00e9 que la prot\u00e9ine de la membrane nucl\u00e9aire interne Man1 emp\u00eache l&#039;accumulation de Lamine A dans les cellules humaines. Nous d\u00e9terminerons si Man1 agit \u00e9galement pour limiter l&#039;accumulation de prog\u00e9rine, la forme mutante de Lamine A qui cause le syndrome de Hutchison-Gilford Progeria (HGPS), et si oui, si cette voie repr\u00e9sente une nouvelle cible th\u00e9rapeutique qui retarde ou pr\u00e9vient l&#039;accumulation de prog\u00e9rine chez les enfants atteints de HGPS.<\/p>\n<p>Topher Carroll \u00e9tait \u00e9tudiant dipl\u00f4m\u00e9 dans le laboratoire de David Morgan \u00e0 l&#039;Universit\u00e9 de Californie \u00e0 San Francisco, o\u00f9 il a \u00e9tudi\u00e9 l&#039;enzymologie du complexe promoteur de l&#039;anaphase. Il est ensuite all\u00e9 dans le laboratoire d&#039;Aaron Straight au d\u00e9partement de biochimie de l&#039;Universit\u00e9 de Stanford pour explorer les m\u00e9canismes \u00e9pig\u00e9n\u00e9tiques qui r\u00e9gulent l&#039;assemblage et la propagation du centrom\u00e8re. Topher a cr\u00e9\u00e9 son propre laboratoire au d\u00e9partement de biologie cellulaire de l&#039;Universit\u00e9 Yale au printemps 2012. Son laboratoire s&#039;int\u00e9resse \u00e0 l&#039;organisation nucl\u00e9aire et \u00e0 sa relation avec la structure de la chromatine et les maladies humaines.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2013-4\u2033 module_id=\u201d2013-4\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Juin 2013 (date de d\u00e9but 1er septembre 2013) :\u00a0<\/strong>Au Dr Katharine Ullman : Universit\u00e9 de l\u2019Utah, Salt Lake City, UT ; \u00ab \u00c9lucider l\u2019impact de la prog\u00e9rine sur le r\u00f4le de Nup153 dans la r\u00e9ponse aux dommages \u00e0 l\u2019ADN \u00bb.<\/p>\n<p><strong><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Ullman.jpg\" width=\"150\" height=\"176\" \/><\/strong>Ce projet vise \u00e0 mieux comprendre l\u2019\u00e9tiologie du syndrome de Hutchinson-Gilford Progeria (HGPS) en \u00e9tudiant la fa\u00e7on dont la mutation de la lamine A \u2013 qui entra\u00eene l\u2019expression d\u2019une forme mut\u00e9e de la lamine A appel\u00e9e prog\u00e9rine \u2013 alt\u00e8re la fonction de la prot\u00e9ine Nup153, en particulier dans le contexte des dommages \u00e0 l\u2019ADN. Nup153 est un composant d\u2019une grande structure appel\u00e9e complexe de pores nucl\u00e9aires et il a \u00e9t\u00e9 r\u00e9cemment reconnu qu\u2019elle participe \u00e0 la r\u00e9ponse cellulaire aux dommages \u00e0 l\u2019ADN. On sait que la lamine A interagit avec Nup153 et participe \u00e9galement \u00e0 la r\u00e9ponse aux dommages \u00e0 l\u2019ADN. Nous \u00e9tudierons cette intersection fonctionnelle et nous nous appuierons sur ces connexions dans le but d\u2019int\u00e9grer rapidement de nouvelles informations dans le contexte du HGPS.<\/p>\n<p>Katie Ullman a obtenu une licence \u00e0 l&#039;universit\u00e9 Northwestern, puis a \u00e9tudi\u00e9 \u00e0 l&#039;universit\u00e9 Stanford pour son doctorat. Apr\u00e8s un stage postdoctoral \u00e0 l&#039;universit\u00e9 de Californie \u00e0 San Diego, elle a rejoint la facult\u00e9 de l&#039;universit\u00e9 de l&#039;Utah en 1998. Katie est membre des d\u00e9partements des sciences oncologiques et de biochimie, ainsi que chercheuse au Huntsman Cancer Institute. Elle a re\u00e7u un Career Award en sciences biom\u00e9dicales du Burroughs Wellcome Fund et codirige le programme de r\u00e9ponse et de r\u00e9gulation cellulaires au sein du Cancer Center.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2013-5\u2033 module_id=\u201d2013-5\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Juin 2013 (date de d\u00e9but 1er septembre 2013) :\u00a0<\/strong>Au Dr Katherine Wilson : Johns Hopkins School of Medicine, Baltimore, MD ; \u00ab Expression naturelle de la prog\u00e9rine et cons\u00e9quences de la r\u00e9duction de l&#039;O-GlcNAcylation de la queue de la lamine A \u00bb.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Katherine%20Wilson.jpg\" width=\"150\" height=\"181\" \/>La prog\u00e9rine a \u00e9t\u00e9 consid\u00e9r\u00e9e comme une forme \u00ab non naturelle \u00bb de la lamine A. Cependant, de nouveaux travaux sugg\u00e8rent que la prog\u00e9rine est exprim\u00e9e \u00e0 des niveaux \u00e9lev\u00e9s \u00e0 deux moments et endroits sp\u00e9cifiques du corps humain : apr\u00e8s la naissance, lorsque le c\u0153ur du nouveau-n\u00e9 est en cours de remodelage (fermeture du canal art\u00e9riel), et dans les cellules (fibroblastes) expos\u00e9es \u00e0 la lumi\u00e8re ultraviolette (UV-A). Cela sugg\u00e8re que la prog\u00e9rine est un produit g\u00e9n\u00e9tique naturel qui s&#039;exprime \u00e0 des moments pr\u00e9cis, pour des raisons sp\u00e9cifiques (inconnues). Une compr\u00e9hension de base de ces r\u00f4les \u00ab naturels \u00bb propos\u00e9s de la prog\u00e9rine pourrait permettre d&#039;identifier de nouvelles voies qui pourraient \u00eatre cibl\u00e9es th\u00e9rapeutiquement dans le HGPS. En commen\u00e7ant par des c\u0153urs de vache nouveau-n\u00e9s et des fibroblastes irradi\u00e9s aux UVA, ce projet purifiera et identifiera les prot\u00e9ines qui s&#039;associent \u00e0 la prog\u00e9rine et \u00e9valuera leur impact connu ou potentiel sur le HGPS. Nous testerons \u00e9galement la possibilit\u00e9 que la prog\u00e9rine \u00e9chappe \u00e0 la r\u00e9gulation par une enzyme essentielle (&#039;OGT&#039; ; O-GlcNAc Transf\u00e9rase) qui normalement &#039;marque&#039; la queue de la lamine A avec de nombreuses copies d&#039;un petit sucre (&#039;GlcNAc&#039;). Ce projet permettra d&#039;identifier les sites modifi\u00e9s par le sucre dans la lamine A par rapport \u00e0 la prog\u00e9rine, de se demander si ces modifications favorisent des fonctions saines de la lamine et de d\u00e9terminer si elles sont influenc\u00e9es par des m\u00e9dicaments dans les essais cliniques HGPS.<\/p>\n<p>Katherine Wilson, PhD, Katherine L. Wilson a grandi dans le nord-ouest du Pacifique. Elle a \u00e9tudi\u00e9 la microbiologie \u00e0 Seattle (BS, University of Washington), la biochimie et la g\u00e9n\u00e9tique \u00e0 San Francisco (PhD, UCSF) et a commenc\u00e9 \u00e0 explorer la structure nucl\u00e9aire en tant que boursi\u00e8re postdoctorale \u00e0 San Diego (UCSD). Elle a ensuite rejoint la facult\u00e9 de la Johns Hopkins University School of Medicine \u00e0 Baltimore, o\u00f9 elle est professeur de biologie cellulaire. Son laboratoire \u00e9tudie le \u00ab trio \u00bb de prot\u00e9ines (lamines, prot\u00e9ines du domaine LEM et leur partenaire \u00e9nigmatique, BAF) qui forment la structure nucl\u00e9aire de la \u00ab lamina \u00bb, pour comprendre comment les mutations de ces prot\u00e9ines provoquent une dystrophie musculaire, une maladie cardiaque, une lipodystrophie, le syndrome de Hutchinson-Gilford Progeria et le syndrome de Nestor-Guillermo Progeria.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2013-6\u2033 module_id=\u201d2013-6\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Juin 2013 (date de d\u00e9but 1er septembre 2013) :\u00a0<\/strong>Au Dr Brian Kennedy, Buck Institute for Research on Aging, Novato, CA ; \u00ab Intervention contre le vieillissement par petites mol\u00e9cules dans la prog\u00e9ria \u00bb.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/KennedyMug.jpg\" width=\"150\" height=\"157\" \/>Il participe activement \u00e0 la recherche sur le vieillissement dans la r\u00e9gion du Pacifique, qui compte la plus grande population \u00e2g\u00e9e au monde. Il est professeur invit\u00e9 \u00e0 l&#039;Institut de recherche sur le vieillissement du Guangdong Medical College en Chine. Il est \u00e9galement professeur affili\u00e9 au d\u00e9partement de biochimie de l&#039;universit\u00e9 de Washington \u00e0 Seattle.<\/p>\n<p>Les mutations des lamines nucl\u00e9aires de type A donnent lieu \u00e0 une s\u00e9rie de maladies appel\u00e9es laminopathies, qui sont associ\u00e9es aux maladies cardiovasculaires, \u00e0 la dystrophie musculaire et \u00e0 la prog\u00e9ria. Parmi celles-ci, un sous-ensemble affecte le traitement de la lamine A en C-terminal et donne lieu \u00e0 des syndromes prog\u00e9ro\u00efdes qui ressemblent \u00e0 un vieillissement acc\u00e9l\u00e9r\u00e9. La question de savoir si les prog\u00e9rias sont ou non m\u00e9caniquement li\u00e9es aux \u00e9v\u00e9nements qui entra\u00eenent le vieillissement normal a tourment\u00e9 le domaine du vieillissement pendant des d\u00e9cennies en ce qui concerne les syndromes de Werner et de Hutchison-Gilford Progeria. De petites mol\u00e9cules ont r\u00e9cemment \u00e9t\u00e9 identifi\u00e9es qui ralentissent le vieillissement (rapamycine) et prot\u00e8gent contre les maladies chroniques li\u00e9es \u00e0 l&#039;\u00e2ge (rapamycine et resv\u00e9ratrol). Si la prog\u00e9ria est m\u00e9caniquement li\u00e9e au vieillissement normal, ces petites mol\u00e9cules et d&#039;autres qui \u00e9mergent pourraient \u00eatre des agents efficaces dans le traitement du HGPS. Dans cette \u00e9tude, le laboratoire du Dr Kennedy pr\u00e9voit d&#039;utiliser des mod\u00e8les murins de prog\u00e9ria pour \u00e9valuer l&#039;efficacit\u00e9 du resv\u00e9ratrol et de la rapamycine (ainsi que des d\u00e9riv\u00e9s des deux agents) pour am\u00e9liorer la pathologie de la maladie.<\/p>\n<p>Brian K. Kennedy, Ph. D., est pr\u00e9sident et directeur g\u00e9n\u00e9ral du Buck Institute for Research on Aging. Il est reconnu \u00e0 l&#039;\u00e9chelle internationale pour ses recherches sur la biologie fondamentale du vieillissement et comme un visionnaire d\u00e9termin\u00e9 \u00e0 traduire les d\u00e9couvertes de la recherche en de nouvelles fa\u00e7ons de d\u00e9tecter, de pr\u00e9venir et de traiter les maladies li\u00e9es \u00e0 l&#039;\u00e2ge. Il s&#039;agit notamment des maladies d&#039;Alzheimer et de Parkinson, du cancer, des accidents vasculaires c\u00e9r\u00e9braux, du diab\u00e8te et des maladies cardiaques. Il dirige une \u00e9quipe de 20 chercheurs principaux au Buck Institute, tous impliqu\u00e9s dans des recherches interdisciplinaires visant \u00e0 prolonger les ann\u00e9es de vie en bonne sant\u00e9.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2012-1\u2033 module_id=\u201d2012-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2012 (date de d\u00e9but ao\u00fbt 2013) : \u00a0<\/strong>Au Dr Gerardo Ferbeyre, Ph. D., Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Canada : \u00ab Contr\u00f4le de la clairance de la prog\u00e9rine par d\u00e9farn\u00e9sylation et phosphorylation de la s\u00e9rine 22 \u00bb<\/p>\n<p>L&#039;accumulation de prog\u00e9rine, une forme alt\u00e9r\u00e9e de la lamine A, est \u00e0 l&#039;origine du syndrome de Hutchinson-Gilford Progeria. Le traitement id\u00e9al de la maladie devrait emp\u00eacher l&#039;accumulation de prog\u00e9rine en diminuant sa synth\u00e8se ou en favorisant sa d\u00e9gradation. Cependant, on sait peu de choses sur le renouvellement normal de la lamine A ou de la prog\u00e9rine. L&#039;accumulation de prog\u00e9rine dans la lamina nucl\u00e9aire est contr\u00f4l\u00e9e par la farn\u00e9sylation. Nous avons d\u00e9couvert que la farn\u00e9sylation de la lamine A contr\u00f4le sa phosphorylation au niveau de la s\u00e9rine 22, un \u00e9v\u00e9nement pr\u00e9c\u00e9demment li\u00e9 \u00e0 la d\u00e9polym\u00e9risation de la lamina nucl\u00e9aire pendant la mitose. Cependant, nous avons d\u00e9couvert que la phosphorylation de S22 se produit \u00e9galement pendant l&#039;interphase et est associ\u00e9e \u00e0 la g\u00e9n\u00e9ration de fragments de clivage de la prog\u00e9rine. Nous proposons une nouvelle voie de renouvellement de la prog\u00e9rine qui comprend la d\u00e9farn\u00e9sylation et la phosphorylation de S22. Nous pensons qu&#039;une compr\u00e9hension mol\u00e9culaire de cette voie peut conduire \u00e0 de nouvelles possibilit\u00e9s th\u00e9rapeutiques pour la prog\u00e9ria. En particulier, l&#039;identification des kinases et des phosphatases r\u00e9gulant la phosphorylation de la lamine A au niveau de la s\u00e9rine 22 et des prot\u00e9ases m\u00e9diant le renouvellement de la lamine A aidera \u00e0 identifier les m\u00e9dicaments qui stimulent le renouvellement de la prog\u00e9rine et am\u00e9liorent les patients atteints de HGPS.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/G%20Ferbeyre.jpg\" alt=\"\" width=\"150\" height=\"189\" \/>Le Dr Gerardo Ferbeyre a obtenu son dipl\u00f4me de m\u00e9decine \u00e0 l&#039;Universit\u00e9 de La Havane, \u00e0 Cuba, en 1987 et est titulaire d&#039;un doctorat en biochimie de l&#039;Universit\u00e9 de Montr\u00e9al, au Canada, o\u00f9 il a \u00e9tudi\u00e9 les ribozymes. Il a effectu\u00e9 une formation postdoctorale au laboratoire de Cold Spring Harbor avec le Dr Scott Lowe. Il y a \u00e9tabli un lien entre la prot\u00e9ine de leuc\u00e9mie promy\u00e9locytaire PML et la s\u00e9nescence induite par les oncog\u00e8nes et a \u00e9tudi\u00e9 le r\u00f4le de p53 et p19ARF comme m\u00e9diateurs de la s\u00e9nescence cellulaire. En octobre 2001, le Dr Ferbeyre s&#039;est joint au D\u00e9partement de biochimie de l&#039;Universit\u00e9 de Montr\u00e9al pour poursuivre ses recherches scientifiques sur la s\u00e9nescence et les possibilit\u00e9s de r\u00e9activer la prot\u00e9ine de leuc\u00e9mie promy\u00e9locytaire pour traiter les cancers. Les contributions r\u00e9centes de son laboratoire comprennent la d\u00e9couverte que la signalisation des dommages \u00e0 l&#039;ADN m\u00e9die la s\u00e9nescence et un lien entre les d\u00e9fauts d&#039;expression de la lamine A et la s\u00e9nescence.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2012-2\u2033 module_id=\u201d2012-2\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2012 (date de d\u00e9but f\u00e9vrier 2013) :\u00a0<\/strong>Au Dr Thomas Misteli, PhD, National Cancer Institute NIH, Bethesda, MD : \u00ab D\u00e9couverte de petites mol\u00e9cules dans le HGPS \u00bb<\/p>\n<p>L&#039;\u00e9quipe du Dr Misteli d\u00e9veloppe de nouvelles strat\u00e9gies th\u00e9rapeutiques pour la prog\u00e9ria. Les travaux de son groupe visent \u00e0 interf\u00e9rer avec la production de la prot\u00e9ine prog\u00e9rine \u00e0 l&#039;aide d&#039;outils mol\u00e9culaires et \u00e0 trouver de nouvelles petites mol\u00e9cules pour contrer les effets n\u00e9fastes de la prog\u00e9rine dans les cellules des patients. Ces efforts conduiront \u00e0 une compr\u00e9hension d\u00e9taill\u00e9e de la biologie cellulaire des cellules prog\u00e9ria et nous rapprocheront d&#039;une th\u00e9rapie mol\u00e9culaire cibl\u00e9e pour la prog\u00e9ria.<br \/>\n<img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/MISTELI_portrait2007small.jpg\" alt=\"\" width=\"150\" height=\"130\" \/><\/p>\n<p>Tom Misteli est un biologiste cellulaire de renomm\u00e9e internationale qui a \u00e9t\u00e9 le pionnier de l&#039;utilisation des approches d&#039;imagerie pour \u00e9tudier les g\u00e9nomes et l&#039;expression des g\u00e8nes dans les cellules vivantes. Il est chercheur principal et directeur associ\u00e9 au National Cancer Institute, NIH. L&#039;int\u00e9r\u00eat de son laboratoire est de d\u00e9couvrir les principes fondamentaux de l&#039;organisation spatiale du g\u00e9nome et d&#039;appliquer ces connaissances au d\u00e9veloppement de nouvelles strat\u00e9gies diagnostiques et th\u00e9rapeutiques pour le cancer et le vieillissement. Il a re\u00e7u de nombreux prix, dont la m\u00e9daille d&#039;or de l&#039;universit\u00e9 Charles, le prix Flemming, le prix Gian-Tondury, le prix du directeur du NIH et un prix du m\u00e9rite du NIH. Il agit en tant que conseiller pour de nombreuses agences nationales et internationales et si\u00e8ge \u00e0 plusieurs comit\u00e9s de r\u00e9daction, dont Cell. Il est r\u00e9dacteur en chef du Journal of Cell Biology et de Current Opinion in Cell Biology.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2012-3\u2033 module_id=\u201d2012-3\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2012 (date de d\u00e9but avril ou mai 2013) :\u00a0<\/strong>\u00c0 Karima Djabali, PhD, Universit\u00e9 technique de Munich, Munich, Allemagne : \u00ab Dynamique de la prog\u00e9rine au cours de la progression du cycle cellulaire \u00bb<\/p>\n<p>Le syndrome de Hutchinson-Gilford progeria (HGPS) est caus\u00e9 par des mutations du g\u00e8ne de la lamine A, qui entra\u00eenent la production et l&#039;accumulation d&#039;une prot\u00e9ine mutante de la pr\u00e9lamine A appel\u00e9e prog\u00e9rine. \u00c9tant donn\u00e9 que cette prot\u00e9ine s&#039;accumule et interf\u00e8re avec les composants et les fonctions nucl\u00e9aires, l&#039;identification des effecteurs directs de la prog\u00e9rine pendant la mitose et la diff\u00e9renciation est essentielle pour comprendre comment et quand la prog\u00e9rine d\u00e9clenche les d\u00e9fauts nucl\u00e9aires qui conduisent les cellules \u00e0 une s\u00e9nescence pr\u00e9matur\u00e9e.<\/p>\n<p>Dans cette \u00e9tude, le laboratoire du Dr Djabali pr\u00e9voit d&#039;identifier les effecteurs directs de la prog\u00e9rine dans l&#039;\u00e9chafaudage nucl\u00e9aire, l&#039;enveloppe nucl\u00e9aire et l&#039;int\u00e9rieur du noyau afin de d\u00e9terminer les interactions mol\u00e9culaires initiales perturb\u00e9es par l&#039;expression de la prog\u00e9rine. \u00c0 cette fin, ils utiliseront des anticorps anti-prog\u00e9rine et des mod\u00e8les cellulaires HGPS, notamment des fibroblastes et des cellules pr\u00e9curseurs d\u00e9riv\u00e9es de la peau \u00e9tablies \u00e0 partir de biopsies cutan\u00e9es provenant de patients atteints de HGPS (PRF Cell Bank). Ils combineront l&#039;imagerie biochimique et cellulaire pour identifier les effecteurs de la prog\u00e9rine et \u00e9tudier leur contribution aux \u00e9v\u00e9nements mol\u00e9culaires conduisant aux changements ph\u00e9notypiques typiques observ\u00e9s dans les cellules HGPS qui sont responsables du d\u00e9veloppement de la maladie HGPS. Les connaissances acquises gr\u00e2ce \u00e0 ces \u00e9tudes permettront d&#039;identifier de nouvelles cibles th\u00e9rapeutiques pour le traitement du HGPS et de nouveaux crit\u00e8res d&#039;\u00e9valuation cellulaires pour tester l&#039;efficacit\u00e9 des interventions potentielles. Nous esp\u00e9rons que notre travail fournira les connaissances n\u00e9cessaires pour nous rapprocher, ainsi que d&#039;autres \u00e9quipes du domaine du HGPS, de la d\u00e9couverte d&#039;un ou de plusieurs rem\u00e8des qui aideront les enfants atteints de HGPS \u00e0 vivre une vie plus longue et plus saine.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/djabali-photo.jpg\" alt=\"\" width=\"150\" height=\"225\" \/><\/p>\n<p>Karima Djabali, PhD, est professeure d&#039;\u00e9pig\u00e9n\u00e9tique du vieillissement \u00e0 la Facult\u00e9 de m\u00e9decine, au D\u00e9partement de dermatologie et \u00e0 l&#039;Institut d&#039;ing\u00e9nierie m\u00e9dicale (IMETUM) de l&#039;Universit\u00e9 technique de Munich, en Allemagne. Le Dr Djabali a obtenu sa ma\u00eetrise et son doctorat en biochimie \u00e0 l&#039;Universit\u00e9 Paris VII. Elle a effectu\u00e9 ses travaux de th\u00e8se au Coll\u00e8ge de France (laboratoire du Prof. F. Gros, France) et \u00e0 l&#039;Universit\u00e9 Rockefeller (laboratoire du Prof. G. Blobel, USA). Elle a effectu\u00e9 ses recherches postdoctorales \u00e0 l&#039;EMBL (Heidelberg, Allemagne). Fran\u00e7ais Elle a \u00e9t\u00e9 charg\u00e9e de recherche au Centre national de la recherche scientifique (CNRS, France) en 1994 et a \u00e9t\u00e9 chercheuse associ\u00e9e au d\u00e9partement de dermatologie de l&#039;universit\u00e9 Columbia de New York (\u00c9tats-Unis) de 1999 \u00e0 2003. Par la suite, le Dr Djabali a \u00e9t\u00e9 professeure adjointe au d\u00e9partement de dermatologie de l&#039;universit\u00e9 Columbia de New York (\u00c9tats-Unis) de 2004 \u00e0 2009. Les recherches du Dr Djabali portent sur le vieillissement cellulaire dans les \u00e9tats normaux et pathologiques, avec un accent particulier sur la pathog\u00e9n\u00e8se mol\u00e9culaire et cellulaire des maladies du vieillissement pr\u00e9matur\u00e9, telles que le syndrome de Hutchinson-Gilford progeria (HGPS). Ses recherches combinent la biologie mol\u00e9culaire, la biologie cellulaire, la g\u00e9n\u00e9tique et la prot\u00e9omique pour identifier les voies de signalisation associ\u00e9es au vieillissement cellulaire afin de d\u00e9velopper des strat\u00e9gies pr\u00e9ventives pour retarder et\/ou corriger les processus de vieillissement.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2012-4\u2033 module_id=\u201d2012-4\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Septembre 2012 :\u00a0<\/strong>\u00c0 Tom Misteli, Ph. D., National Cancer Institute, NIH, Bethesda, MD; Prix du technicien<\/p>\n<p>Le laboratoire du Dr Misteli cherche \u00e0 identifier les compos\u00e9s principaux pour le d\u00e9veloppement de m\u00e9dicaments HGPS en analysant de grandes biblioth\u00e8ques de mol\u00e9cules chimiques. La bourse de sp\u00e9cialit\u00e9 a \u00e9t\u00e9 utilis\u00e9e pour acheter l&#039;\u00e9quipement de laboratoire robotis\u00e9 n\u00e9cessaire \u00e0 ces \u00e9tudes.<\/p>\n<p>Tom Misteli est un biologiste cellulaire de renomm\u00e9e internationale qui a \u00e9t\u00e9 le pionnier de l&#039;utilisation des approches d&#039;imagerie pour \u00e9tudier les g\u00e9nomes et l&#039;expression des g\u00e8nes dans les cellules vivantes. Il est chercheur principal et directeur associ\u00e9 au National Cancer Institute, NIH. L&#039;int\u00e9r\u00eat de son laboratoire est de d\u00e9couvrir les principes fondamentaux de l&#039;organisation spatiale du g\u00e9nome et d&#039;appliquer ces connaissances au d\u00e9veloppement de nouvelles strat\u00e9gies diagnostiques et th\u00e9rapeutiques pour le cancer et le vieillissement. Il a re\u00e7u de nombreux prix, dont la m\u00e9daille d&#039;or de l&#039;universit\u00e9 Charles, le prix Flemming, le prix Gian-Tondury, le prix du directeur du NIH et un prix du m\u00e9rite du NIH. Il agit en tant que conseiller pour de nombreuses agences nationales et internationales et si\u00e8ge \u00e0 plusieurs comit\u00e9s de r\u00e9daction, notamment\u00a0<em>Cellule.\u00a0<\/em>Il est le r\u00e9dacteur en chef de\u00a0<em>Journal de biologie cellulaire\u00a0<\/em>et de<em>\u00a0Opinion actuelle en biologie cellulaire.<\/em><br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2012-5\u2033 module_id=\u201d2012-5\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Juillet 2012 (date de d\u00e9but 1er septembre 2012) :\u00a0<\/strong>\u00c0 Vicente Andr\u00e9s Garc\u00eda, PhD, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Espagne ; &quot;Quantification de la prog\u00e9rine farn\u00e9syl\u00e9e et identification des g\u00e8nes qui activent les aberrants\u00a0<em>LMNA<\/em>\u00a0\u00e9pissage dans le syndrome de Hutchinson-Gilford Progeria\u201d<\/p>\n<p>Le syndrome de Hutchinson-Gilford progeria (HGPS) est une maladie g\u00e9n\u00e9tique rare et mortelle caract\u00e9ris\u00e9e par un vieillissement pr\u00e9matur\u00e9 et un d\u00e9c\u00e8s \u00e0 un \u00e2ge moyen de 13 ans. La plupart des patients atteints de HGPS sont porteurs d&#039;une mutation dans le g\u00e8ne\u00a0<em>LMNA<\/em>\u00a0(codant principalement la lamine A et la lamine C) qui conduit \u00e0 la production de \u00ab prog\u00e9rine \u00bb, une prot\u00e9ine anormale qui conserve une modification farn\u00e9syle toxique. Des exp\u00e9riences sur des mod\u00e8les cellulaires et murins de HGPS ont d\u00e9montr\u00e9 de mani\u00e8re concluante que la quantit\u00e9 totale de prog\u00e9rine farn\u00e9syl\u00e9e et le rapport prog\u00e9rine\/lamine A mature d\u00e9terminent la gravit\u00e9 de la maladie dans la prog\u00e9ria et constituent un facteur cl\u00e9 de la dur\u00e9e de vie. Des essais cliniques en cours \u00e9valuent donc l&#039;efficacit\u00e9 des m\u00e9dicaments qui inhibent la farn\u00e9sylation de la prog\u00e9rine chez les patients atteints de HGPS. L&#039;objectif principal de ce projet est de d\u00e9velopper une m\u00e9thode permettant de quantifier de mani\u00e8re routini\u00e8re et pr\u00e9cise l&#039;expression de la prog\u00e9rine et son niveau de farn\u00e9sylation, ainsi que le rapport prog\u00e9rine\/lamine A mature, dans les cellules des patients atteints de HGPS. La mesure de ces param\u00e8tres aidera \u00e0 \u00e9valuer l&#039;efficacit\u00e9 des m\u00e9dicaments ciblant la farn\u00e9sylation de la prog\u00e9rine, ainsi que celle des futures strat\u00e9gies con\u00e7ues pour inhiber le traitement anormal (\u00e9pissage) de la\u00a0<em>LMNA<\/em>\u00a0L&#039;ARNm, cause du HGPS chez la plupart des patients. Un objectif secondaire est de r\u00e9aliser des \u00e9tudes pilotes pour le d\u00e9veloppement d&#039;une strat\u00e9gie \u00e0 haut d\u00e9bit pour identifier les m\u00e9canismes qui activent les anomalies\u00a0<em>LMNA<\/em>\u00a0\u00e9pissage.<\/p>\n<p>Vicente Andr\u00e9s a obtenu son doctorat en sciences biologiques \u00e0 l&#039;Universit\u00e9 de Barcelone (1990). Au cours de sa formation postdoctorale \u00e0 l&#039;h\u00f4pital pour enfants de l&#039;Universit\u00e9 Harvard (1991-1994) et au centre m\u00e9dical St. Elizabeth de l&#039;Universit\u00e9 Tufts (1994-1995), il a men\u00e9 des \u00e9tudes sur le r\u00f4le des facteurs de transcription hom\u00e9obox et MEF2 dans les processus de diff\u00e9renciation et de prolif\u00e9ration cellulaires ; c&#039;est \u00e9galement au cours de cette p\u00e9riode qu&#039;il a d\u00e9velopp\u00e9 un int\u00e9r\u00eat pour la recherche cardiovasculaire. Sa carri\u00e8re de chercheur ind\u00e9pendant a d\u00e9but\u00e9 en 1995 lorsqu&#039;il a \u00e9t\u00e9 nomm\u00e9 professeur adjoint de m\u00e9decine \u00e0 Tufts. Depuis lors, le Dr Andr\u00e9s et son groupe ont \u00e9tudi\u00e9 le remodelage vasculaire au cours de l&#039;ath\u00e9roscl\u00e9rose et de la rest\u00e9nose post-angioplastie, et plus r\u00e9cemment, ils ont \u00e9tudi\u00e9 le r\u00f4le de l&#039;enveloppe nucl\u00e9aire dans la r\u00e9gulation de la transduction du signal, de l&#039;expression g\u00e9n\u00e9tique et de l&#039;activit\u00e9 du cycle cellulaire dans les maladies cardiovasculaires et le vieillissement, en mettant l&#039;accent sur les lamines de type A et le syndrome de prog\u00e9ria de Hutchinson-Gilford (HGPS).<\/p>\n<p>Apr\u00e8s avoir obtenu un poste de chercheur scientifique titulaire au Conseil national de la recherche scientifique (CSIC), le Dr Andr\u00e9s est retourn\u00e9 en Espagne en 1999 pour cr\u00e9er son groupe de recherche \u00e0 l&#039;Institut de biom\u00e9decine de Valence, o\u00f9 il a travaill\u00e9 comme professeur titulaire. Depuis 2006, son groupe est membre du R\u00e9seau th\u00e9matique de recherche coop\u00e9rative sur les maladies cardiovasculaires (RECAVA). Il a rejoint le Centre national de recherche cardiovasculaire (CNIC) en septembre 2009. En 2010, il a re\u00e7u le prix Docteur Leon Dumont de la Soci\u00e9t\u00e9 belge de cardiologie.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2012-6\u2033 module_id=\u201d2012-6\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Juillet 2012 (date de d\u00e9but 1er septembre 2012) :\u00a0<\/strong>Au Dr Samuel Benchimol, Universit\u00e9 York, Toronto, Canada : \u00ab Implication de p53 dans la s\u00e9nescence pr\u00e9matur\u00e9e du HGPS \u00bb<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Benchimol.jpg\" alt=\"\" width=\"150\" height=\"170\" \/>Le Dr Benchimol a une longue exp\u00e9rience dans le domaine de la fonction de p53. Il utilisera son expertise pour s&#039;appuyer sur des donn\u00e9es pr\u00e9liminaires intrigantes et tester de nouvelles hypoth\u00e8ses concernant le r\u00f4le de p53 dans la m\u00e9diation de la s\u00e9nescence pr\u00e9matur\u00e9e montr\u00e9e par les cellules des patients atteints du syndrome de Hutchinson-Gilford Progeria (HGPS). Le premier objectif est con\u00e7u pour tester l&#039;hypoth\u00e8se selon laquelle la prog\u00e9rine provoque un stress de r\u00e9plication, qui \u00e0 son tour provoque un arr\u00eat de la croissance de la s\u00e9nescence, et que p53 agit en aval du stress de r\u00e9plication induit par la prog\u00e9rine. Cet objectif est suivi d&#039;un objectif plus m\u00e9caniste qui vise \u00e0 d\u00e9terminer comment la prog\u00e9rine et p53 collaborent pour provoquer une r\u00e9ponse de s\u00e9nescence.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2012-7\u2033 module_id=\u201d2012-7\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<\/p>\n<p class=\"justifyleft\"><strong>Juillet 2012 :\u00a0<\/strong>\u00c0 Tom Misteli, Ph. D., National Cancer Institute, NIH, Bethesda, MD ; Modification de la bourse de sp\u00e9cialit\u00e9<\/p>\n<p>Le laboratoire du Dr Misteli cherche \u00e0 identifier les compos\u00e9s principaux pour le d\u00e9veloppement de m\u00e9dicaments HGPS en analysant de grandes biblioth\u00e8ques de mol\u00e9cules chimiques. La bourse de sp\u00e9cialit\u00e9 a \u00e9t\u00e9 utilis\u00e9e pour acheter l&#039;\u00e9quipement de laboratoire robotis\u00e9 n\u00e9cessaire \u00e0 ces \u00e9tudes.<\/p>\n<p>Tom Misteli est un biologiste cellulaire de renomm\u00e9e internationale qui a \u00e9t\u00e9 le pionnier de l&#039;utilisation des approches d&#039;imagerie pour \u00e9tudier les g\u00e9nomes et l&#039;expression des g\u00e8nes dans les cellules vivantes. Il est chercheur principal et directeur associ\u00e9 au National Cancer Institute, NIH. L&#039;int\u00e9r\u00eat de son laboratoire est de d\u00e9couvrir les principes fondamentaux de l&#039;organisation spatiale du g\u00e9nome et d&#039;appliquer ces connaissances au d\u00e9veloppement de nouvelles strat\u00e9gies diagnostiques et th\u00e9rapeutiques pour le cancer et le vieillissement. Il a re\u00e7u de nombreux prix, dont la m\u00e9daille d&#039;or de l&#039;universit\u00e9 Charles, le prix Flemming, le prix Gian-Tondury, le prix du directeur du NIH et un prix du m\u00e9rite du NIH. Il agit en tant que conseiller pour de nombreuses agences nationales et internationales et si\u00e8ge \u00e0 plusieurs comit\u00e9s de r\u00e9daction, notamment\u00a0<em>Cellule.\u00a0<\/em>Il est le r\u00e9dacteur en chef de\u00a0<em>Journal de biologie cellulaire\u00a0<\/em>et de<em>\u00a0Opinion actuelle en biologie cellulaire.<\/em><br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2011-1\u2033 module_id=\u201d2011-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2011 (date de d\u00e9but 1er mars 2012) :\u00a0<\/strong>Au Dr Thomas Dechat, PhD, Universit\u00e9 de m\u00e9decine de Vienne, Autriche ; \u00ab Association membranaire stable de la prog\u00e9rine et implications pour la signalisation pRb<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Dechat.jpg\" alt=\"\" width=\"150\" height=\"167\" \/>Les lamines de type A sont des prot\u00e9ines structurelles importantes du noyau des cellules de mammif\u00e8res. Elles sont les principaux composants d&#039;un maillage filamenteux situ\u00e9 \u00e0 la surface interne de l&#039;enveloppe nucl\u00e9aire et fournissent non seulement la forme et la stabilit\u00e9 m\u00e9canique du noyau, mais sont \u00e9galement impliqu\u00e9es dans des processus cellulaires essentiels tels que la r\u00e9plication de l&#039;ADN et l&#039;expression des g\u00e8nes. Outre leur localisation \u00e0 la p\u00e9riph\u00e9rie nucl\u00e9aire, un pool suppl\u00e9mentaire plus dynamique de lamines de type A est pr\u00e9sent \u00e0 l&#039;int\u00e9rieur du noyau, ce qui est sugg\u00e9r\u00e9 comme \u00e9tant important pour la prolif\u00e9ration et la diff\u00e9renciation cellulaires appropri\u00e9es. Au cours des treize derni\u00e8res ann\u00e9es, plus de 300 mutations du g\u00e8ne codant les lamines de type A ont \u00e9t\u00e9 associ\u00e9es \u00e0 diverses maladies humaines, y compris le syndrome de Hutchinson-Gilford Progeria (HGPS), une maladie du vieillissement pr\u00e9matur\u00e9. Les m\u00e9canismes mol\u00e9culaires de la maladie sont encore mal compris, ce qui entrave le d\u00e9veloppement de strat\u00e9gies th\u00e9rapeutiques efficaces. La mutation du g\u00e8ne de la lamine de type A associ\u00e9e au HGPS entra\u00eene la production d&#039;une prot\u00e9ine mutante de la lamine A, appel\u00e9e prog\u00e9rine. Contrairement \u00e0 la lamine A normale, la prog\u00e9rine est ancr\u00e9e de mani\u00e8re stable \u00e0 la membrane nucl\u00e9aire, ce qui alt\u00e8re les propri\u00e9t\u00e9s m\u00e9caniques du noyau. Notre hypoth\u00e8se de travail propose que la prog\u00e9rine ancr\u00e9e \u00e0 la membrane affecte \u00e9galement gravement le pool dynamique de lamines \u00e0 l&#039;int\u00e9rieur du noyau et donc la prolif\u00e9ration et la diff\u00e9renciation cellulaires.<\/p>\n<p>L&#039;un des objectifs de ce projet est d&#039;identifier les m\u00e9canismes responsables de l&#039;ancrage de la prog\u00e9rine \u00e0 la membrane nucl\u00e9aire et de trouver des moyens d&#039;inhiber sp\u00e9cifiquement cet ancrage membranaire dans la perspective de sauver le pool dynamique de lamines et ainsi d&#039;inverser les ph\u00e9notypes cellulaires associ\u00e9s au HGPS. Des r\u00e9sultats ant\u00e9rieurs montrent que ce pool dynamique de lamines dans un complexe avec d&#039;autres prot\u00e9ines r\u00e9gule la prolif\u00e9ration cellulaire via la voie de la prot\u00e9ine du r\u00e9tinoblastome (pRb). Pour \u00e9tayer notre hypoth\u00e8se, il a r\u00e9cemment \u00e9t\u00e9 d\u00e9montr\u00e9 que dans les cellules de patients atteints de HGPS, la voie pRb est effectivement alt\u00e9r\u00e9e. Dans le deuxi\u00e8me objectif de notre projet, nous proposons d&#039;\u00e9tudier les effets de la prog\u00e9rine sur la r\u00e9gulation, la dynamique et les activit\u00e9s du pool mobile de lamines A nucl\u00e9oplasmiques et de ses prot\u00e9ines associ\u00e9es et son impact sur la signalisation pRb au niveau mol\u00e9culaire. Les r\u00e9sultats de notre \u00e9tude devraient faire la lumi\u00e8re sur les m\u00e9canismes mol\u00e9culaires responsables de la maladie derri\u00e8re le HGPS et pourraient aider \u00e0 identifier de nouvelles cibles m\u00e9dicamenteuses et des m\u00e9dicaments pour des th\u00e9rapies plus efficaces et cibl\u00e9es.<\/p>\n<p>Le Dr Dechat a obtenu sa ma\u00eetrise et son doctorat en biochimie \u00e0 l&#039;Universit\u00e9 de Vienne, en Autriche. Apr\u00e8s un an en tant que postdoctorant au d\u00e9partement de recherche neuromusculaire de l&#039;Universit\u00e9 de m\u00e9decine de Vienne, il a \u00e9t\u00e9 postdoctorant dans le laboratoire du professeur Robert Goldman, de l&#039;Universit\u00e9 Northwestern, Feinberg Medical School, Chicago, Illinois de 2004 \u00e0 2009, travaillant sur la caract\u00e9risation structurelle et fonctionnelle des lamines nucl\u00e9aires en bonne sant\u00e9 et en maladie, en se concentrant principalement sur les m\u00e9canismes conduisant au syndrome de Hutchinson-Gilford Progeria en raison de l&#039;expression de la prog\u00e9rine. Depuis 2010, il est professeur adjoint aux laboratoires Max F. Perutz de l&#039;Universit\u00e9 de m\u00e9decine de Vienne, o\u00f9 il \u00e9tudie les propri\u00e9t\u00e9s structurelles et fonctionnelles des lamines nucl\u00e9oplasmiques de type A et de LAP2 au cours du cycle cellulaire et dans diverses maladies associ\u00e9es \u00e0 des mutations des lamines A\/C et LAP2.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2011-2\u2033 module_id=\u201d2011-2\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2011 (date de d\u00e9but 1er mars 2012) :\u00a0<\/strong>\u00e0 Maria Eriksson, Ph.D., Institut Karolinska, Su\u00e8de ; Analyse de la possibilit\u00e9 d&#039;inversion de la maladie de Progeria<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Eriksson.jpg\" alt=\"\" width=\"150\" height=\"124\" \/>Dans cette \u00e9tude, le laboratoire du Dr Eriksson pr\u00e9voit d&#039;utiliser son mod\u00e8le r\u00e9cemment d\u00e9velopp\u00e9 pour la prog\u00e9ria avec expression de la mutation du g\u00e8ne LMNA la plus courante dans l&#039;os. Ils ont d\u00e9j\u00e0 montr\u00e9 que la suppression de l&#039;expression de la mutation de la prog\u00e9ria apr\u00e8s le d\u00e9veloppement de la maladie cutan\u00e9e prog\u00e9ria conduisait \u00e0 une inversion presque compl\u00e8te du ph\u00e9notype de la maladie (Sagelius, Rosengardten et al. 2008). La progression de la maladie prog\u00e9ria sera surveill\u00e9e dans le tissu osseux \u00e0 diff\u00e9rents moments apr\u00e8s l&#039;inhibition de la mutation pour analyser la possibilit\u00e9 d&#039;inversion de la maladie. Leurs r\u00e9sultats pr\u00e9liminaires indiquent une am\u00e9lioration des sympt\u00f4mes cliniques et sont prometteurs pour l&#039;identification d&#039;un traitement et d&#039;une gu\u00e9rison possibles de cette maladie.<\/p>\n<p>Le Dr Eriksson a obtenu sa ma\u00eetrise en biologie mol\u00e9culaire \u00e0 l&#039;universit\u00e9 d&#039;Ume\u00e5, en Su\u00e8de, en 1996, et son doctorat en neurologie \u00e0 l&#039;Institut Karolinska en 2001. Elle a \u00e9t\u00e9 chercheuse postdoctorale \u00e0 l&#039;Institut national de recherche sur le g\u00e9nome humain, Instituts nationaux de la sant\u00e9 de 2001 \u00e0 2003, et est chercheuse principale\/chef de groupe de recherche et professeure adjointe au d\u00e9partement des biosciences et de la nutrition de l&#039;Institut Karolinska depuis 2003. Elle est \u00e9galement professeure agr\u00e9g\u00e9e en g\u00e9n\u00e9tique m\u00e9dicale \u00e0 l&#039;Institut Karolinska. Ses domaines de recherche comprennent la prog\u00e9ria et les m\u00e9canismes g\u00e9n\u00e9tiques du vieillissement.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2011-3\u2033 module_id=\u201d2011-3\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<\/p>\n<p class=\"justifyleft\"><strong>D\u00e9cembre 2011 (date de d\u00e9but 1er mars 2012) :\u00a0<\/strong>\u00c0 Colin L. Stewart D.Phil, Institut de biologie m\u00e9dicale, Singapour ; \u00ab D\u00e9finition de la base mol\u00e9culaire de la d\u00e9t\u00e9rioration du muscle lisse vasculaire dans la prog\u00e9ria<\/p>\n<p>Les enfants atteints de prog\u00e9ria meurent d&#039;une maladie cardiovasculaire, soit d&#039;une crise cardiaque, soit d&#039;un accident vasculaire c\u00e9r\u00e9bral. Au cours de la derni\u00e8re d\u00e9cennie, il est devenu \u00e9vident que les vaisseaux sanguins de l&#039;enfant sont l&#039;un des principaux tissus touch\u00e9s par la prog\u00e9ria. La prog\u00e9ria semble affaiblir la paroi musculaire des vaisseaux sanguins en provoquant d&#039;une mani\u00e8re ou d&#039;une autre la mort des cellules musculaires lisses. Cela peut non seulement fragiliser les vaisseaux, mais aussi stimuler la formation de plaque conduisant \u00e0 l&#039;obstruction des vaisseaux. Les deux r\u00e9sultats entra\u00eenent une d\u00e9faillance des vaisseaux sanguins et, si celle-ci se produit dans les vaisseaux du c\u0153ur, cela entra\u00eenera une crise cardiaque.<\/p>\n<p>Colin Stewart et son coll\u00e8gue Oliver Dreesen pr\u00e9voient d&#039;\u00e9tudier comment la forme d\u00e9fectueuse de la prot\u00e9ine nucl\u00e9aire Lamine A (prog\u00e9rine) affecte sp\u00e9cifiquement la croissance et la survie des cellules musculaires lisses des vaisseaux sanguins. En utilisant la technologie des cellules souches, Colin et ses coll\u00e8gues ont pu obtenir des cellules souches \u00e0 partir de cellules cutan\u00e9es \u00e9tablies \u00e0 partir de deux enfants atteints de prog\u00e9ria. Ces cellules souches sp\u00e9cifiques au patient ont ensuite \u00e9t\u00e9 transform\u00e9es en cellules musculaires lisses ressemblant \u00e0 celles des vaisseaux sanguins. Curieusement, ces cellules musculaires lisses ont produit des niveaux de prog\u00e9rine parmi les plus \u00e9lev\u00e9s, par rapport aux autres types de cellules, ce qui sugg\u00e8re une raison possible pour laquelle les vaisseaux sanguins sont gravement touch\u00e9s par la prog\u00e9ria. Les cellules musculaires lisses contenant de la prog\u00e9rine ont montr\u00e9 des signes de dommages \u00e0 l&#039;ADN dans le noyau de la cellule. Colin et Oliver utiliseront ces cellules et d&#039;autres cellules d\u00e9riv\u00e9es des cellules souches pour comprendre quel type d&#039;ADN est endommag\u00e9 et quels processus biochimiques, n\u00e9cessaires \u00e0 la survie des cellules musculaires lisses, sont affect\u00e9s par la prog\u00e9rine. En \u00e9tant en mesure d\u2019\u00e9tudier directement les cellules musculaires lisses recr\u00e9\u00e9es \u00e0 partir d\u2019enfants atteints de prog\u00e9ria, ils esp\u00e8rent identifier exactement ce qui ne va pas avec les cellules afin de d\u00e9velopper de nouvelles proc\u00e9dures pour tester de nouveaux m\u00e9dicaments qui pourraient \u00e9ventuellement aider \u00e0 traiter les enfants atteints.<\/p>\n<p>Colin Stewart a obtenu son doctorat \u00e0 l&#039;Universit\u00e9 d&#039;Oxford o\u00f9 il a \u00e9tudi\u00e9 les interactions entre les t\u00e9ratocarcinomes, les pr\u00e9curseurs des cellules souches embryonnaires, et les premiers embryons de souris. Apr\u00e8s un travail postdoctoral avec Rudolf Jaenisch \u00e0 Hambourg, il a \u00e9t\u00e9 chercheur \u00e0 l&#039;EMBL \u00e0 Heidelberg. Il a jou\u00e9 un r\u00f4le d\u00e9terminant dans la d\u00e9couverte du r\u00f4le de la cytokine LIF dans le maintien des cellules souches embryonnaires de souris. Il a \u00e9galement initi\u00e9 son int\u00e9r\u00eat pour les lamines nucl\u00e9aires et l&#039;architecture nucl\u00e9aire dans le d\u00e9veloppement. Il a poursuivi ses \u00e9tudes sur les lamines, les cellules souches et l&#039;empreinte g\u00e9nomique apr\u00e8s avoir \u00e9t\u00e9 transf\u00e9r\u00e9 au Roche Institute of Molecular Biology dans le New Jersey. En 1996, il rejoint le programme de recherche ABL \u00e0 Frederick, dans le Maryland, et en 1999, il est nomm\u00e9 chef du laboratoire de canc\u00e9rologie et de biologie du d\u00e9veloppement au National Cancer Institute. Au cours de la derni\u00e8re d\u00e9cennie, ses int\u00e9r\u00eats se sont concentr\u00e9s sur l&#039;architecture fonctionnelle du noyau cellulaire dans les cellules souches, la r\u00e9g\u00e9n\u00e9ration, le vieillissement et la maladie, en particulier en ce qui concerne la mani\u00e8re dont les fonctions nucl\u00e9aires sont int\u00e9gr\u00e9es \u00e0 la dynamique du cytosquelette dans le d\u00e9veloppement et la maladie. Depuis juin 2007, il est chercheur principal et directeur adjoint \u00e0 l&#039;Institut de biologie m\u00e9dicale de Singapore Biopolis.<\/p>\n<p>Oliver Dreesen est actuellement chercheur principal \u00e0 l&#039;Institut de biologie m\u00e9dicale de Singapour. Apr\u00e8s avoir obtenu son dipl\u00f4me de premier cycle \u00e0 Berne, en Suisse, Oliver a occup\u00e9 des postes de recherche \u00e0 l&#039;Institut Pasteur de Paris et \u00e0 l&#039;Universit\u00e9 de Californie \u00e0 San Diego. Il a obtenu son doctorat \u00e0 l&#039;Universit\u00e9 Rockefeller de New York, o\u00f9 il a \u00e9tudi\u00e9 la structure et la fonction des extr\u00e9mit\u00e9s des chromosomes (t\u00e9lom\u00e8res) lors de la variation antig\u00e9nique des trypanosomes africains. Ses recherches actuelles portent sur le r\u00f4le des t\u00e9lom\u00e8res dans les maladies humaines, le vieillissement et la reprogrammation cellulaire.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2011-4\u2033 module_id=\u201d2011-4\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Septembre 2011 (date de d\u00e9but 1er janvier 2012) :\u00a0<\/strong>Au Dr Dylan Taatjes, Universit\u00e9 du Colorado, Boulder, CO : Profil m\u00e9tabolique comparatif des cellules HGPS et \u00e9valuation des changements ph\u00e9notypiques lors de la modulation des m\u00e9tabolites cl\u00e9s<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/taatjes_dylan.jpg\" alt=\"\" width=\"150\" height=\"94\" \/>Le syndrome de Hutchinson-Gilford Progeria (HGPS) est une maladie rare et invalidante caus\u00e9e par une mutation de la prot\u00e9ine lamine A. Des \u00e9tudes ant\u00e9rieures ont identifi\u00e9 les mutations de la prot\u00e9ine lamine A \u00e0 l&#039;origine de la maladie et ont \u00e9valu\u00e9 sa fonction anormale dans des cellules humaines et dans des mod\u00e8les murins de HGPS. Ces informations, associ\u00e9es \u00e0 des \u00e9tudes d&#039;expression \u00e0 l&#039;\u00e9chelle du g\u00e9nome comparant les cellules HGPS \u00e0 celles d&#039;individus non affect\u00e9s, ont consid\u00e9rablement fait progresser notre compr\u00e9hension de cette maladie. Un domaine qui a \u00e9t\u00e9 n\u00e9glig\u00e9 dans la recherche sur le HGPS est une analyse approfondie des changements m\u00e9taboliques qui se produisent dans les cellules HGPS par rapport aux t\u00e9moins sains. Des anomalies m\u00e9taboliques accompagnent de nombreuses maladies humaines (par exemple l&#039;ath\u00e9roscl\u00e9rose, le diab\u00e8te et le cancer), et l&#039;\u00e9valuation clinique du HGPS sugg\u00e8re des anomalies chroniques dans les voies m\u00e9taboliques de base.<\/p>\n<p>Les m\u00e9tabolites cellulaires repr\u00e9sentent les substances biochimiques qui, avec les prot\u00e9ines et les acides nucl\u00e9iques, constituent l\u2019ensemble des mol\u00e9cules d\u2019une cellule. Ainsi, les changements m\u00e9taboliques sont sans doute aussi importants que les changements d\u2019expression g\u00e9n\u00e9tique dans la pathogen\u00e8se des maladies. En effet, le domaine en plein essor de la \u00ab m\u00e9tabolomique \u00bb a d\u00e9j\u00e0 donn\u00e9 lieu \u00e0 de nombreuses d\u00e9couvertes cl\u00e9s reliant\u00a0<em>m\u00e9tabolites simples<\/em>\u00a0Les mutations de la lamine A sont responsables de maladies humaines sp\u00e9cifiques, notamment la leuc\u00e9mie et le cancer m\u00e9tastatique de la prostate. Par cons\u00e9quent, l&#039;identification des m\u00e9tabolites et des voies m\u00e9taboliques alt\u00e9r\u00e9s dans le HGPS devrait permettre de mieux comprendre la pathogen\u00e8se de la maladie et de d\u00e9couvrir des strat\u00e9gies th\u00e9rapeutiques enti\u00e8rement nouvelles. Cela est particuli\u00e8rement pertinent pour le HGPS, car de nombreuses \u00e9tudes in vivo et sur cellules ont d\u00e9montr\u00e9 que les mutations de la lamine A ne causent pas de dommages irr\u00e9versibles et que les ph\u00e9notypes cellulaires du HGPS, s&#039;ils sont correctement trait\u00e9s, peuvent en fait \u00eatre \u00e9limin\u00e9s.<\/p>\n<p>Une fois l&#039;analyse comparative compl\u00e8te des m\u00e9tabolites pr\u00e9sents dans les cellules issues de donneurs sains et de patients atteints de HGPS termin\u00e9e, des analyses biochimiques et cellulaires de suivi permettront de d\u00e9terminer si les principaux m\u00e9tabolites identifi\u00e9s lors de l&#039;analyse peuvent induire des ph\u00e9notypes HGPS dans les cellules saines ou inverser les ph\u00e9notypes HGPS dans les cellules malades. Par cons\u00e9quent, cette \u00e9tude r\u00e9v\u00e9lera non seulement comment les mutations de la lamine A associ\u00e9es au HGPS affectent les voies m\u00e9taboliques globales dans les cellules humaines, mais elle commencera \u00e9galement \u00e0 \u00e9valuer si le ciblage de ces voies repr\u00e9sente une approche efficace pour une intervention th\u00e9rapeutique.<\/p>\n<p>Le laboratoire Taatjes combine une expertise en biochimie, prot\u00e9omique et cryomicroscopie \u00e9lectronique pour \u00e9tudier les m\u00e9canismes fondamentaux qui r\u00e9gulent l&#039;expression des g\u00e8nes humains. Le laboratoire met \u00e9galement en \u0153uvre des approches g\u00e9nomiques et m\u00e9tabolomiques pour aider \u00e0 relier les r\u00e9sultats m\u00e9canistiques aux cons\u00e9quences physiologiques. Les \u00e9tudes m\u00e9tabolomiques men\u00e9es au laboratoire Taatjes, en conjonction avec des \u00e9tudes m\u00e9canistiques avec un isoforme p53 qui provoque un vieillissement acc\u00e9l\u00e9r\u00e9, servent de base \u00e0 cette \u00e9tude HGPS.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2011-5\u2033 module_id=\u201d2011-5\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Juin 2011 (date de d\u00e9but 1er janvier 2012) :\u00a0<\/strong>\u00e0 Jan Lammerding, PhD, Institut Weill de biologie cellulaire et mol\u00e9culaire de l&#039;Universit\u00e9 Cornell, Ithaca, NY ; Dysfonctionnement des cellules musculaires lisses vasculaires dans le syndrome de Hutchinson-Gilford-Progeria<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/JanLammerding.jpg\" alt=\"\" width=\"150\" height=\"217\" \/>Le syndrome de Hutchinson-Gilford progeria (HGPS) est caus\u00e9 par des mutations du g\u00e8ne codant les lamines A et C. Les enfants atteints de HGPS d\u00e9veloppent une perte de cheveux, des d\u00e9fauts osseux, une perte de tissu adipeux et d&#039;autres signes de vieillissement acc\u00e9l\u00e9r\u00e9 avant de succomber \u00e0 un accident vasculaire c\u00e9r\u00e9bral ou \u00e0 un infarctus du myocarde au d\u00e9but de leur adolescence. Des \u00e9tudes post-mortem r\u00e9v\u00e8lent une perte spectaculaire de cellules musculaires lisses vasculaires dans les plus gros vaisseaux sanguins des patients atteints de HGPS. Les cellules musculaires lisses vasculaires sont essentielles au fonctionnement normal des vaisseaux sanguins, et la perte de cellules musculaires lisses vasculaires peut constituer la force motrice de la maladie cardiovasculaire mortelle dans le cas du HGPS.<\/p>\n<p>Nous avons d\u00e9j\u00e0 d\u00e9montr\u00e9 que les cellules cutan\u00e9es des patients atteints de HGPS sont plus sensibles au stress m\u00e9canique, ce qui entra\u00eene une augmentation de la mort cellulaire lorsqu&#039;elles sont soumises \u00e0 des \u00e9tirements r\u00e9p\u00e9titifs. Dans ce projet, nous allons v\u00e9rifier si une sensibilit\u00e9 accrue au stress m\u00e9canique est \u00e9galement responsable de la perte progressive des cellules musculaires lisses vasculaires dans le HGPS, car les gros vaisseaux sanguins sont expos\u00e9s \u00e0 des contraintes vasculaires r\u00e9p\u00e9titives \u00e0 chaque battement de c\u0153ur. Combin\u00e9e \u00e0 une alt\u00e9ration de la reconstitution des cellules endommag\u00e9es, la sensibilit\u00e9 m\u00e9canique accrue pourrait entra\u00eener la perte progressive des cellules musculaires lisses vasculaires et le d\u00e9veloppement de maladies cardiovasculaires dans le HGPS.<\/p>\n<p>Pour \u00e9tudier l&#039;effet du stress m\u00e9canique sur les cellules musculaires lisses vasculaires in vivo, nous utiliserons des proc\u00e9dures chirurgicales pour augmenter localement la pression art\u00e9rielle ou pour cr\u00e9er des l\u00e9sions vasculaires dans les gros vaisseaux sanguins, puis comparerons l&#039;effet sur la survie et la r\u00e9g\u00e9n\u00e9ration des cellules musculaires lisses vasculaires dans un mod\u00e8le murin de HGPS et chez des t\u00e9moins sains. Les connaissances acquises gr\u00e2ce \u00e0 ces \u00e9tudes apporteront de nouvelles informations sur les m\u00e9canismes mol\u00e9culaires sous-jacents \u00e0 la maladie cardiovasculaire dans le HGPS et pourraient offrir de nouvelles pistes pour le d\u00e9veloppement d&#039;approches th\u00e9rapeutiques.<\/p>\n<p>Le Dr Lammerding est professeur adjoint \u00e0 l&#039;universit\u00e9 Cornell au d\u00e9partement de g\u00e9nie biom\u00e9dical et au Weill Institute for Cell and Molecular Biology. Avant de rejoindre l&#039;universit\u00e9 Cornell en 2011, le Dr Lammerding a travaill\u00e9 comme professeur adjoint au d\u00e9partement de m\u00e9decine de la Harvard Medical School\/Brigham and Women&#039;s Hospital et a \u00e9t\u00e9 charg\u00e9 de cours au Massachusetts Institute of Technology. Le laboratoire Lammerding \u00e9tudie la biom\u00e9canique subcellulaire et la r\u00e9ponse de signalisation cellulaire \u00e0 la stimulation m\u00e9canique, en se concentrant plus particuli\u00e8rement sur la fa\u00e7on dont les mutations dans les prot\u00e9ines de l&#039;enveloppe nucl\u00e9aire telles que les lamines peuvent rendre les cellules plus sensibles au stress m\u00e9canique et affecter leur signalisation de m\u00e9canotransduction. Les connaissances acquises gr\u00e2ce \u00e0 ces travaux peuvent conduire \u00e0 une meilleure compr\u00e9hension du m\u00e9canisme mol\u00e9culaire sous-jacent \u00e0 diverses laminopathies, un groupe diversifi\u00e9 de maladies dont le syndrome de prog\u00e9ria de Hutchison-Gilford, la dystrophie musculaire d&#039;Emery-Dreifuss et la lipodystrophie partielle familiale.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2010-1\u2033 module_id=\u201d2010-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2010 (date de d\u00e9but 1er avril 2011) :\u00a0<\/strong>\u00c0 Robert D. Goldman, PhD, Northwestern University Medical School, Chicago, IL ; Un r\u00f4le pour les lamines de type B dans la prog\u00e9ria<\/p>\n<p>Les lamines nucl\u00e9aires de type A et B sont des prot\u00e9ines situ\u00e9es dans le noyau de la cellule. Ces prot\u00e9ines forment des r\u00e9seaux structurels distincts mais interactifs au sein du noyau. Les lamines sont essentielles pour d\u00e9terminer la taille, la forme et les propri\u00e9t\u00e9s m\u00e9caniques du noyau ; elles fournissent un \u00e9chafaudage intranucl\u00e9aire pour l&#039;organisation des chromosomes. Nous avons d\u00e9couvert que lorsqu&#039;un r\u00e9seau de lamines est alt\u00e9r\u00e9 par une mutation conduisant \u00e0 un dysfonctionnement, l&#039;autre est \u00e9galement alt\u00e9r\u00e9. Bien que les formes typiques et atypiques du syndrome de Hutchinson Gilford Progeria soient caus\u00e9es par diff\u00e9rentes mutations du g\u00e8ne de la lamine nucl\u00e9aire A, nous avons d\u00e9couvert que les r\u00e9seaux de lamines de type B dans les cellules des patients atteints de progeria sont \u00e9galement anormalement alt\u00e9r\u00e9s. Les lamines de type B sont exprim\u00e9es dans toutes les cellules somatiques \u00e0 partir de la f\u00e9condation, et on sait qu&#039;elles jouent un r\u00f4le important dans la r\u00e9gulation de nombreuses fonctions nucl\u00e9aires, notamment la r\u00e9plication de l&#039;ADN et la transcription des g\u00e8nes. Pourtant, peu d&#039;attention a \u00e9t\u00e9 accord\u00e9e aux isoformes de la lamine B et \u00e0 leurs r\u00f4les dans la progeria. Dans cette proposition, notre objectif est de d\u00e9terminer les effets de l&#039;expression de la prog\u00e9rine, la forme mutante la plus fr\u00e9quemment rencontr\u00e9e de la lamine A, et d&#039;autres mutations atypiques de la lamine A de la prog\u00e9ria sur l&#039;expression, la structure et la fonction des lamines de type B. Nos \u00e9tudes pr\u00e9liminaires sugg\u00e8rent que les changements dans les r\u00e9seaux de lamines de type B sont des m\u00e9diateurs importants de la pathologie cellulaire dans le HGPS, en raison de leurs interactions avec les lamines de type A. Nous examinerons les changements dans les lamines de type B dans les cellules de patients atteints de prog\u00e9ria et leurs relations avec les d\u00e9fauts de croissance cellulaire et la s\u00e9nescence pr\u00e9matur\u00e9e. Nous \u00e9tudierons \u00e9galement les effets de l&#039;inhibition de la farn\u00e9syltransf\u00e9rase sur l&#039;expression, la modification et la stabilit\u00e9 des lamines de type B. Ceci est important car les lamines de type B sont normalement farn\u00e9syl\u00e9es de mani\u00e8re stable. Ces \u00e9tudes propos\u00e9es sont particuli\u00e8rement opportunes compte tenu des essais cliniques en cours impliquant des patients atteints de prog\u00e9ria utilisant des m\u00e9dicaments qui inhibent la farn\u00e9sylation des prot\u00e9ines. Nos \u00e9tudes promettent d&#039;apporter de nouvelles perspectives sur les m\u00e9canismes mol\u00e9culaires responsables du vieillissement pr\u00e9matur\u00e9 des cellules chez les patients atteints de cette maladie d\u00e9vastatrice. Les r\u00e9sultats de nos recherches devraient r\u00e9v\u00e9ler des informations sur des cibles potentielles suppl\u00e9mentaires \u00e0 prendre en compte dans le d\u00e9veloppement de nouvelles th\u00e9rapies pour les patients atteints de HGPS.<\/p>\n<p>Robert D. Goldman, Ph. D., est professeur Stephen Walter Ranson et pr\u00e9sident du d\u00e9partement de biologie cellulaire et mol\u00e9culaire de la Feinberg School of Medicine de l&#039;universit\u00e9 Northwestern \u00e0 Chicago. Le Dr Goldman a obtenu son doctorat en biologie de l&#039;universit\u00e9 de Princeton et a effectu\u00e9 des recherches postdoctorales \u00e0 l&#039;universit\u00e9 de Londres et au MRC Institute of Virology de Glasgow. Il a \u00e9t\u00e9 membre du corps professoral de la Case Western Reserve University, de l&#039;universit\u00e9 Carnegie-Mellon et a \u00e9t\u00e9 chercheur invit\u00e9 au Cold Spring Harbor Laboratory avant de rejoindre Northwestern. Il est largement reconnu comme une autorit\u00e9 sur la structure et la fonction des syst\u00e8mes de filaments interm\u00e9diaires nucl\u00e9osquelettiques et cytosquelettiques. Au d\u00e9but des ann\u00e9es 1980, il a \u00e9t\u00e9 fascin\u00e9 par la d\u00e9couverte que les lamines \u00e9taient la forme nucl\u00e9aire des filaments interm\u00e9diaires. Depuis lors, son laboratoire de recherche a montr\u00e9 que les lamines nucl\u00e9aires d\u00e9terminent la taille et la forme du noyau et qu&#039;elles sont des facteurs d&#039;une importance cruciale dans le d\u00e9sassemblage et le r\u00e9assemblage du noyau lors de la division cellulaire. Son groupe de recherche a \u00e9galement d\u00e9montr\u00e9 que les lamines s&#039;assemblent dans un \u00e9chafaudage mol\u00e9culaire au sein du noyau cellulaire n\u00e9cessaire \u00e0 la r\u00e9plication de l&#039;ADN, \u00e0 la transcription et \u00e0 l&#039;organisation de la chromatine. Ces derni\u00e8res ann\u00e9es, son int\u00e9r\u00eat pour les lamines s&#039;est concentr\u00e9 sur l&#039;impact des mutations de la lamine A qui donnent naissance au syndrome de Hutchinson Gilford Progeria, une maladie de vieillissement pr\u00e9matur\u00e9, et \u00e0 d&#039;autres formes atypiques de progeria. Cela l&#039;a conduit \u00e0 rechercher les r\u00f4les des lamines dans l&#039;organisation des chromosomes, dans la r\u00e9gulation des modifications \u00e9pig\u00e9n\u00e9tiques de la chromatine et dans la prolif\u00e9ration et la s\u00e9nescence cellulaires.<\/p>\n<p>Le Dr Goldman est membre de l&#039;American Association for the Advancement of Science (AAAS) et a re\u00e7u le prix Ellison Medical Foundation Senior Scholar et le prix NIH MERIT. C&#039;est un \u00e9crivain prolifique, il a \u00e9dit\u00e9 de nombreux volumes pour Cold Spring Harbor Laboratory Press et est r\u00e9dacteur en chef adjoint du FASEB Journal et de Molecular Biology of the Cell. Il a \u00e9t\u00e9 \u00e9lu \u00e0 de nombreux postes dans des soci\u00e9t\u00e9s scientifiques, notamment au conseil d&#039;administration de l&#039;AAAS, au conseil et au pr\u00e9sident de l&#039;American Society for Cell Biology, et a \u00e9t\u00e9 pr\u00e9sident de l&#039;American Association of Anatomy, Cell Biology and Neuroscience Chairs. Il a si\u00e9g\u00e9 \u00e0 de nombreux comit\u00e9s d&#039;\u00e9valuation de l&#039;American Cancer Society et du NIH, est directeur du Whitman Center du Marine Biological Laboratory et est fr\u00e9quemment invit\u00e9 \u00e0 organiser et \u00e0 prendre la parole lors de r\u00e9unions internationales ici et \u00e0 l&#039;\u00e9tranger.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2010-2\u2033 module_id=\u201d2010-2\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2010 :\u00a0<\/strong>\u00c0 John Graziotto, PhD, Massachusetts General Hospital, Boston, MA ; \u00c9limination de la prot\u00e9ine prog\u00e9rine comme cible th\u00e9rapeutique dans le syndrome de Hutchinson-Gilford de la prog\u00e9ria<\/p>\n<p>Le syndrome de Hutchinson-Gilford-Progeria (HGPS) est caus\u00e9 par une mutation du g\u00e8ne de la lamine A, qui entra\u00eene la production et l&#039;accumulation d&#039;une prot\u00e9ine mutante appel\u00e9e prog\u00e9rine. \u00c9tant donn\u00e9 que cette prot\u00e9ine s&#039;accumule, il est important de d\u00e9terminer comment elle est d\u00e9grad\u00e9e d&#039;un point de vue th\u00e9rapeutique. L&#039;objectif de ce travail est de d\u00e9terminer les voies de clairance cellulaire responsables de la d\u00e9gradation de la prot\u00e9ine prog\u00e9rine. Gr\u00e2ce \u00e0 ces informations, nous esp\u00e9rons pouvoir manipuler ces voies pour faciliter la clairance de la prog\u00e9rine, dans le but d&#039;am\u00e9liorer les th\u00e9rapies actuelles ou futures pour le HGPS.<\/p>\n<p>Le Dr Graziotto est chercheur postdoctoral au d\u00e9partement de neurologie du Massachusetts General Hospital. Il travaille actuellement dans le laboratoire du Dr Dimitri Krainc. L&#039;un des principaux objectifs du laboratoire est l&#039;\u00e9tude des troubles neurod\u00e9g\u00e9n\u00e9ratifs dans lesquels des prot\u00e9ines mutantes s&#039;accumulent et forment des agr\u00e9gats. Le laboratoire \u00e9tudie les m\u00e9canismes de clairance de ces prot\u00e9ines afin d&#039;identifier les modificateurs de ces voies qui pourraient conduire \u00e0 de futures cibles th\u00e9rapeutiques.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2010-3\u2033 module_id=\u201d2010-3\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2010 (Date de d\u00e9but 1er avril 2011) :<\/strong>\u00a0\u00c0 Tom Glover, PhD, U Michigan, Ann Arbor, MI ; \u00ab Identification des g\u00e8nes de la prog\u00e9ria et du vieillissement pr\u00e9matur\u00e9 par s\u00e9quen\u00e7age de l&#039;exome \u00bb.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/glover_m_0_0.jpg\" alt=\"\" width=\"150\" height=\"125\" \/>Le terme \u00ab prog\u00e9ria \u00bb d\u00e9signe un certain nombre de troubles qui pr\u00e9sentent diff\u00e9rents aspects du vieillissement pr\u00e9matur\u00e9 ou de la prog\u00e9ria segmentaire. Il s&#039;agit notamment du HGPS et du MAD, tous deux associ\u00e9s \u00e0 des mutations du g\u00e8ne LMNA, ainsi que des troubles de r\u00e9paration de l&#039;ADN, les syndromes de Cockayne et de Werner. De plus, il existe un certain nombre de cas de prog\u00e9ria \u00ab atypique \u00bb pr\u00e9sentant des caract\u00e9ristiques qui se chevauchent mais qui sont distinctes. Le PRF a collect\u00e9 des lign\u00e9es cellulaires et\/ou de l&#039;ADN sur 12 cas de prog\u00e9ria atypique, ce qui repr\u00e9sente la plus grande cohorte jamais constitu\u00e9e. Les ADN ont \u00e9t\u00e9 examin\u00e9s pour rechercher des mutations de l&#039;exon LMNA et aucune n&#039;a \u00e9t\u00e9 trouv\u00e9e. Ils sont actuellement test\u00e9s pour rechercher des mutations ZMPSTE dans le laboratoire du Dr Glover. De plus, ils ont des ph\u00e9notypes distincts des syndromes classiques de Werner et de Cockayne. Par cons\u00e9quent, ces individus pr\u00e9sentent des mutations dans des g\u00e8nes de prog\u00e9ria uniques. Comme la plupart de ces cas sont sporadiques, cela a \u00e9t\u00e9 une t\u00e2che ardue. Cependant, au cours des derni\u00e8res ann\u00e9es, d&#039;\u00e9normes progr\u00e8s techniques ont \u00e9t\u00e9 r\u00e9alis\u00e9s dans le domaine du s\u00e9quen\u00e7age de l&#039;ADN. Le s\u00e9quen\u00e7age des exons du g\u00e9nome entier, ou \u00ab s\u00e9quen\u00e7age de l&#039;exome \u00bb, a \u00e9t\u00e9 utilis\u00e9 avec succ\u00e8s pour identifier des g\u00e8nes mutants pour un certain nombre de traits monog\u00e9niques, notamment le syndrome de Miller, le syndrome de Kabuki, le retard mental non sp\u00e9cifique, le syndrome de Perrault et bien d&#039;autres, avec de nombreuses autres \u00e9tudes en cours, notamment de nombreuses \u00e9tudes sur\u00a0<em>de novo<\/em>\u00a0Les mutations g\u00e9n\u00e9tiques constituent un outil puissant pour l&#039;identification des g\u00e8nes et il est pr\u00e9vu que dans les prochaines ann\u00e9es, nous comprendrons la cause g\u00e9n\u00e9tique de la plupart des caract\u00e8res monog\u00e9niques.<\/p>\n<p>Au vu de ces avanc\u00e9es technologiques et de la disponibilit\u00e9 de patients similaires, le Dr Glover \u00e9met l\u2019hypoth\u00e8se que les mutations responsables de la prog\u00e9ria atypique peuvent \u00eatre identifi\u00e9es par s\u00e9quen\u00e7age complet de l\u2019exome de ces \u00e9chantillons de patients. L\u2019identification de ces mutations est essentielle pour comprendre l\u2019\u00e9tiologie de la maladie, d\u00e9velopper des traitements efficaces et d\u00e9velopper des connaissances sur les voies mol\u00e9culaires et cellulaires qui se croisent et interagissent dans les prog\u00e9rias et le vieillissement normal. Cependant, cela est difficile \u00e9tant donn\u00e9 qu\u2019il s\u2019agit apparemment de mutations de novo et que les ph\u00e9notypes sont h\u00e9t\u00e9rog\u00e8nes. Le r\u00e9sultat imm\u00e9diat de cette \u00e9tude sera la d\u00e9couverte de 7 \u00e0 15 nouvelles mutations probablement d\u00e9l\u00e9t\u00e8res pour chaque famille, partag\u00e9es par les membres de la famille touch\u00e9s et pouvant \u00eatre uniques \u00e0 la famille. L\u2019analyse conjointe de ces g\u00e8nes dans 6 \u00e0 12 familles pourrait bien r\u00e9v\u00e9ler des cas d\u2019all\u00e8les d\u00e9l\u00e9t\u00e8res distincts du m\u00eame g\u00e8ne, ou diff\u00e9rents d\u00e9fauts dans la m\u00eame voie fonctionnelle, apparaissant dans plusieurs familles, offrant ainsi le premier aper\u00e7u de nouveaux g\u00e8nes\/voies candidats pour la prog\u00e9ria. Si les r\u00e9sultats sont concluants, leur impact pourrait \u00eatre consid\u00e9rable et concerner directement non seulement le patient concern\u00e9 mais aussi, en raison de caract\u00e9ristiques communes, d\u2019autres formes de prog\u00e9ria, y compris le HGPS, ainsi que le vieillissement normal.<\/p>\n<p>Le Dr Glover est professeur au d\u00e9partement de g\u00e9n\u00e9tique humaine et de p\u00e9diatrie de l&#039;Universit\u00e9 du Michigan. Il est l&#039;auteur de plus de 120 publications de recherche et chapitres de livres. Le Dr Glover participe activement \u00e0 la recherche sur la prog\u00e9ria depuis plus d&#039;une d\u00e9cennie et est membre du comit\u00e9 de recherche m\u00e9dicale de la PRF depuis sa cr\u00e9ation en 2004. Son laboratoire a particip\u00e9 aux efforts de recherche qui ont permis d&#039;identifier pour la premi\u00e8re fois les mutations du g\u00e8ne LMNA dans le HGPS et de d\u00e9montrer que les inhibiteurs de la farnyslyation peuvent inverser les anomalies nucl\u00e9aires des cellules HGPS, ouvrant la voie \u00e0 des essais cliniques. L&#039;un des principaux int\u00e9r\u00eats de son laboratoire est l&#039;\u00e9tude des m\u00e9canismes et des cons\u00e9quences de l&#039;instabilit\u00e9 du g\u00e9nome dans les maladies g\u00e9n\u00e9tiques humaines. Les efforts actuels visent \u00e0 comprendre les m\u00e9canismes mol\u00e9culaires impliqu\u00e9s dans la production de mutations du nombre de copies (CNV) dans le g\u00e9nome humain. Il s&#039;agit d&#039;une forme de mutation courante mais r\u00e9cemment reconnue, importante dans la variation humaine normale et dans de nombreuses maladies g\u00e9n\u00e9tiques. Cependant, contrairement \u00e0 d&#039;autres formes de mutation, on ne comprend pas enti\u00e8rement comment elles se forment et les facteurs de risque g\u00e9n\u00e9tiques et environnementaux impliqu\u00e9s.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2010-4\u2033 module_id=\u201d2010-4\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2010 (date de d\u00e9but 1er mars 2011) :\u00a0<\/strong>\u00c0 Yue Zou, PhD, East Tennessee State University, Johnson City, TN ; M\u00e9canismes mol\u00e9culaires de l&#039;instabilit\u00e9 du g\u00e9nome dans le HGPS<\/p>\n<p>L&#039;objectif de ce projet est de d\u00e9finir les bases mol\u00e9culaires de l&#039;anomalie de r\u00e9plication et de l&#039;instabilit\u00e9 du g\u00e9nome dans les cellules atteintes du syndrome de prog\u00e9ria de Hutchinson-Gilford (HGPS). Le HGPS est une maladie dominante du vieillissement pr\u00e9matur\u00e9 et les patients atteints de cette maladie ont une esp\u00e9rance de vie moyenne de seulement 13 ans. La maladie est caus\u00e9e par une mutation ponctuelle en 1822 ou 1824 dans l&#039;exon 11 du g\u00e8ne de la lamine A, qui entra\u00eene la production sporadique d&#039;une prot\u00e9ine mutante de la lamine A avec 50 acides amin\u00e9s tronqu\u00e9s en interne, appel\u00e9e prog\u00e9rine. La lamine A est un composant interne majeur de l&#039;enveloppe nucl\u00e9aire et du squelette des cellules et la pr\u00e9sence de prog\u00e9rine entra\u00eene une morphologie nucl\u00e9aire anormale et une instabilit\u00e9 du g\u00e9nome dans les cellules HGPS. Il est int\u00e9ressant de noter que des \u00e9tudes r\u00e9centes ont montr\u00e9 que la prog\u00e9rine est \u00e9galement produite chez les individus vieillissants normaux et que son niveau semble augmenter avec l&#039;\u00e2ge d&#039;une moyenne de 3% par an dans les art\u00e8res coronaires. Cette augmentation est en concordance avec de nombreux aspects de la pathologie cardiovasculaire chez les patients HGPS et g\u00e9riatriques, impliquant un r\u00f4le potentiellement important de la prog\u00e9rine dans le vieillissement et les maladies li\u00e9es au vieillissement telles que le cancer et les maladies cardiovasculaires.<\/p>\n<p>Bien que la cause g\u00e9n\u00e9tique du HGPS soit connue, les m\u00e9canismes mol\u00e9culaires par lesquels l&#039;action de la prog\u00e9rine conduit \u00e0 des ph\u00e9notypes associ\u00e9s au vieillissement pr\u00e9matur\u00e9 restent loin d&#039;\u00eatre clairs. Nous et d&#039;autres avons r\u00e9cemment d\u00e9montr\u00e9 que le HGPS pr\u00e9sente un ph\u00e9notype d&#039;instabilit\u00e9 du g\u00e9nome caus\u00e9 par l&#039;accumulation cellulaire de cassures double brin de l&#039;ADN (DSB). L&#039;accumulation de DSB est \u00e9galement une cause courante de vieillissement syst\u00e9mique. Nous avons \u00e9galement constat\u00e9 que\u00a0<em>X\u00e9roderma pigmentosum<\/em>\u00a0Le groupe A (XPA) se localise de mani\u00e8re erron\u00e9e sur les sites DSB dans les cellules HGPS, ce qui entra\u00eene une inhibition de la r\u00e9paration des DSB. L&#039;\u00e9puisement de XPA dans les cellules HGPS restaure partiellement la r\u00e9paration des DSB. Sur la base de ces r\u00e9sultats, nous \u00e9mettons l&#039;hypoth\u00e8se que l&#039;accumulation de dommages \u00e0 l&#039;ADN dans les cellules HGPS est probablement due \u00e0 des activit\u00e9s aberrantes au niveau des fourches de r\u00e9plication qui g\u00e9n\u00e8rent des DSB irr\u00e9parables, conduisant \u00e0 un arr\u00eat pr\u00e9coce de la r\u00e9plication ou \u00e0 une s\u00e9nescence r\u00e9plicative. \u00c9tant donn\u00e9 que les cellules HPGS sont caract\u00e9ris\u00e9es par un arr\u00eat pr\u00e9coce de la r\u00e9plication et une s\u00e9nescence r\u00e9plicative pr\u00e9matur\u00e9e, la r\u00e9v\u00e9lation des m\u00e9canismes sous-jacents aux activit\u00e9s d\u00e9fectueuses au niveau des fourches de r\u00e9plication peut \u00eatre la cl\u00e9 pour comprendre les causes des ph\u00e9notypes HGPS. Cette compr\u00e9hension pourrait conduire \u00e0 de nouvelles strat\u00e9gies de traitement de la maladie en intervenant dans les voies mol\u00e9culaires responsables de la maladie. D&#039;autre part, il est bien connu que les patients atteints de HGPS semblent \u00eatre indemnes de cancer. Bien que le m\u00e9canisme reste inconnu, il peut \u00eatre attribu\u00e9 \u00e0 la s\u00e9nescence r\u00e9plicative pr\u00e9matur\u00e9e des cellules HPGS. Dans ce projet de recherche, nous d\u00e9terminerons la base mol\u00e9culaire de l&#039;accumulation de DSB dans les HGPS en nous concentrant sur la compr\u00e9hension de la mani\u00e8re dont les dommages \u00e0 l&#039;ADN sont produits au niveau des fourches de r\u00e9plication. Nous d\u00e9terminerons ensuite si la prog\u00e9rine interagit avec les facteurs de r\u00e9plication de l&#039;ADN et comment cette interaction provoque les anomalies de r\u00e9plication.<\/p>\n<p>Le Dr Zou est professeur au d\u00e9partement de biochimie et de biologie mol\u00e9culaire du Quillen College of Medicine de l&#039;East Tennessee State University. Il a obtenu son doctorat en biophysique en 1991 \u00e0 l&#039;universit\u00e9 Clark. Les recherches du Dr Zou ont principalement port\u00e9 sur la compr\u00e9hension de l&#039;instabilit\u00e9 du g\u00e9nome dans le cancer et des voies associ\u00e9es, notamment la r\u00e9paration de l&#039;ADN et les points de contr\u00f4le des dommages \u00e0 l&#039;ADN. Il s&#039;est r\u00e9cemment int\u00e9ress\u00e9 \u00e0 l&#039;instabilit\u00e9 du g\u00e9nome et aux r\u00e9ponses aux dommages \u00e0 l&#039;ADN dans la prog\u00e9ria caus\u00e9e par une maturation d\u00e9fectueuse de la pr\u00e9lamine A, en particulier le syndrome de Hutchinson-Gilford Progeria, et son groupe a fait des d\u00e9couvertes int\u00e9ressantes sur les m\u00e9canismes mol\u00e9culaires de l&#039;instabilit\u00e9 du g\u00e9nome dans le HGPS.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2010-5\u2033 module_id=\u201d2010-5\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2010 (date de d\u00e9but 1er janvier 2011) :\u00a0<\/strong>\u00c0 Kan Cao, PhD, Universit\u00e9 du Maryland, College Park, MD ; La rapamycine inverse le ph\u00e9notype cellulaire et am\u00e9liore la clairance des prot\u00e9ines mutantes dans le syndrome de Hutchinson Gilford Progeria<\/p>\n<p>Les travaux du Dr Cao porteront sur l&#039;effet de l&#039;Everolimus sur les cellules HGPS, seul ou en association avec le Lanafarnib. Cette \u00e9tude permettra d&#039;\u00e9valuer \u00e0 la fois le potentiel th\u00e9rapeutique et les bases m\u00e9canistiques d&#039;une telle approche th\u00e9rapeutique combinatoire.<\/p>\n<p>Le Dr Cao est professeur adjoint au d\u00e9partement de biologie cellulaire et de g\u00e9n\u00e9tique mol\u00e9culaire de l&#039;Universit\u00e9 du Maryland. Le laboratoire du Dr Cao s&#039;int\u00e9resse \u00e0 l&#039;\u00e9tude des m\u00e9canismes cellulaires de la prog\u00e9ria et du vieillissement normal.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2010-6\u2033 module_id=\u201d2010-6\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Juin 2010 (date de d\u00e9but 1er octobre 2010) :\u00a0<\/strong>\u00c0 Evgeny Makarov, PhD, Universit\u00e9 Brunel, Uxbridge, Royaume-Uni ; Identification des r\u00e9gulateurs d&#039;\u00e9pissage LMNA par prot\u00e9omique comparative des complexes spliceosomal.<\/p>\n<p>Les recherches du Dr Makarov portent sur l&#039;\u00e9pissage des pr\u00e9curseurs d&#039;ARN messager (pr\u00e9-ARNm). L&#039;\u00e9pissage des pr\u00e9-ARNm est un processus cellulaire au cours duquel les s\u00e9quences non codantes (introns) sont supprim\u00e9es et les s\u00e9quences codantes (exons) sont jointes pour g\u00e9n\u00e9rer de l&#039;ARNm destin\u00e9 \u00e0 la production de prot\u00e9ines. L&#039;\u00e9pissage des pr\u00e9-ARNm est quelque peu similaire au montage d&#039;un film : s&#039;il n&#039;est pas effectu\u00e9 correctement, deux sc\u00e8nes non appari\u00e9es peuvent \u00eatre cousues ensemble dans un m\u00eame \u00e9pisode, ce qui n&#039;aurait aucun sens. Lors de l&#039;\u00e9pissage, si les limites exon-intron (sites d&#039;\u00e9pissage) ne sont pas correctement identifi\u00e9es, le mauvais ARNm sera produit. Une prot\u00e9ine d\u00e9fectueuse sera alors synth\u00e9tis\u00e9e et cela peut provoquer une maladie. Pour \u00e9tendre l&#039;analogie, un sc\u00e9nario de film est radicalement modifi\u00e9 par la s\u00e9lection de sc\u00e8nes ; de la m\u00eame mani\u00e8re, dans une cellule vivante, le pr\u00e9-ARNm peut \u00eatre trait\u00e9 de diff\u00e9rentes mani\u00e8res via l&#039;utilisation alternative de diff\u00e9rents sites d&#039;\u00e9pissage. Ce ph\u00e9nom\u00e8ne est appel\u00e9 \u00e9pissage alternatif et permet la production de plusieurs prot\u00e9ines \u00e0 partir d&#039;un seul g\u00e8ne. Le Dr Makarov se concentre actuellement sur l&#039;\u00e9tude de l&#039;\u00e9pissage alternatif associ\u00e9 \u00e0 la maladie. Le principal projet en cours porte sur l&#039;\u00e9tude de l&#039;\u00e9pissage du pr\u00e9-ARNm li\u00e9 au vieillissement du g\u00e8ne humain LMNA, codant les prot\u00e9ines lamines A et C, et en particulier sur son \u00e9pissage aberrant qui provoque le vieillissement pr\u00e9matur\u00e9 des patients atteints du syndrome de Hutchinson Gilford Progeria. L&#039;objectif est d&#039;identifier les prot\u00e9ines modulant les r\u00e9sultats d&#039;\u00e9pissage sp\u00e9cifiques qui, \u00e0 leur tour, sont susceptibles d&#039;affecter la vitesse du processus de vieillissement. \u00c0 cet \u00e9gard, le ciblage pharmaceutique des prot\u00e9ines identifi\u00e9es dans la recherche propos\u00e9e - l&#039;inhibition de leur fonction par de petites mol\u00e9cules en interaction - pourrait conduire \u00e0 la d\u00e9couverte de nouveaux m\u00e9dicaments capables de ralentir le processus de vieillissement. Les autres projets en cours sont : (i) l&#039;\u00e9tude de l&#039;\u00e9pissage alternatif associ\u00e9 au SCLC (cancer du poumon \u00e0 petites cellules) du pr\u00e9-ARNm d&#039;actinine-4 ; (ii) la r\u00e9gulation de l&#039;\u00e9pissage alternatif hTERT comme modalit\u00e9 th\u00e9rapeutique potentielle du cancer.<\/p>\n<p>Le Dr Makarov est n\u00e9 et a grandi \u00e0 Leningrad, en URSS, o\u00f9 il a \u00e9galement obtenu son dipl\u00f4me de l&#039;Universit\u00e9 Polytechnique de Leningrad, D\u00e9partement de Biophysique, en 1980. Il a obtenu son doctorat en biologie mol\u00e9culaire de l&#039;Institut de Physique Nucl\u00e9aire de Leningrad, D\u00e9partement de Biophysique Mol\u00e9culaire et Radiationnelle, en URSS en 1986 pour l&#039;\u00e9tude des m\u00e9canismes mol\u00e9culaires de la biosynth\u00e8se des prot\u00e9ines. Lorsque le rideau de fer a \u00e9t\u00e9 lev\u00e9, il a eu l&#039;opportunit\u00e9 de partir \u00e0 l&#039;\u00e9tranger et a travaill\u00e9 aux \u00c9tats-Unis pendant trois ans de 1990 \u00e0 1993 (Universit\u00e9 de Washington, St. Louis et UC Davis) o\u00f9 il a continu\u00e9 l&#039;\u00e9tude du traitement de l&#039;ARN chez les bact\u00e9ries. En 1993, il s&#039;est install\u00e9 en Europe et a commenc\u00e9 \u00e0 travailler \u00e0 l&#039;\u00c9cole Normale Sup\u00e9rieure de Paris, en France, o\u00f9 il a \u00e9tudi\u00e9 l&#039;efficacit\u00e9 de l&#039;initiation de la traduction. \u00c0 ce moment-l\u00e0, il a commenc\u00e9 \u00e0 penser \u00e0 appliquer son exp\u00e9rience exp\u00e9rimentale de l&#039;\u00e9tude de la traduction procaryote \u00e0 des domaines plus complexes et en d\u00e9veloppement rapide de l&#039;expression des g\u00e8nes eucaryotes. Ainsi, depuis 1994, il a poursuivi ses recherches dans le domaine de l&#039;\u00e9pissage des pr\u00e9-ARNm. En 1997, le Dr Makarov a eu l&#039;occasion rare de rejoindre l&#039;un des plus grands laboratoires dans le domaine du traitement de l&#039;ARN, le laboratoire de Reinhard L\u00fchrmann en Allemagne, o\u00f9 des travaux pionniers ont \u00e9t\u00e9 r\u00e9alis\u00e9s dans l&#039;isolement des petites particules nucl\u00e9aires de ribonucl\u00e9oprot\u00e9ines. Son travail s&#039;est poursuivi dans le laboratoire de L\u00fchrmann jusqu&#039;en 2005, et l&#039;accent de ses recherches a port\u00e9 sur la purification et la caract\u00e9risation des \u00e9pissosomes. En 2007, le Dr Makarov a \u00e9t\u00e9 nomm\u00e9 ma\u00eetre de conf\u00e9rences \u00e0 la Division des biosciences de l&#039;Universit\u00e9 Brunel, \u00e0 l&#039;ouest de Londres, o\u00f9 ses recherches actuelles portent sur l&#039;\u00e9pissage alternatif associ\u00e9 aux maladies.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2009-1\u2033 module_id=\u201d2009-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Octobre 2009 :\u00a0<\/strong>\u00e0 Jason D. Lieb, PhD, Universit\u00e9 de Caroline du Nord, Chapel Hill NC ; Interactions entre les g\u00e8nes et la lamine A\/prog\u00e9rine : une fen\u00eatre sur la compr\u00e9hension de la pathologie et du traitement de la prog\u00e9ria<strong><br \/>\n<\/strong><br \/>\nLe syndrome de Hutchinson-Gilford-Progeria (HGPS) est caus\u00e9 par une mutation du g\u00e8ne de la lamine A, qui entra\u00eene la production d\u2019une prot\u00e9ine raccourcie appel\u00e9e prog\u00e9rine. La lamine A joue normalement un r\u00f4le important dans le maintien de l\u2019organisation du noyau cellulaire, et la mutation qui cr\u00e9e la prog\u00e9rine peut entra\u00eener une d\u00e9sorganisation qui conduit \u00e0 des changements dans la r\u00e9gulation des g\u00e8nes et, en fin de compte, au HGPS. Cependant, on ne sait pas quels g\u00e8nes interagissent avec la lamine A dans les cellules normales, ou avec la prog\u00e9rine dans les cellules des patients atteints de HGPS. Nous \u00e9mettons l\u2019hypoth\u00e8se qu\u2019une liaison ou une dissociation anormale des g\u00e8nes avec la lamine A ou la prog\u00e9rine dans les cellules HGPS provoque une mauvaise r\u00e9gulation des g\u00e8nes, conduisant finalement au HGPS. Pour trouver quels g\u00e8nes interagissent avec la lamine A et la prog\u00e9rine normales dans l\u2019ensemble du g\u00e9nome, le Dr Lieb utilisera une technique appel\u00e9e ChIP-seq. Tout d\u2019abord, il vise \u00e0 identifier les g\u00e8nes qui se lient anormalement \u00e0 la lamine A ou \u00e0 la prog\u00e9rine ou s\u2019en d\u00e9tachent dans les cellules HGPS. Deuxi\u00e8mement, il effectuera une ChIP-seq dans des cellules HGPS trait\u00e9es avec un inhibiteur de la farn\u00e9syltransf\u00e9rase (FTI), qui montre une efficacit\u00e9 partielle dans le traitement des sympt\u00f4mes du HGPS dans des mod\u00e8les de souris. Cette exp\u00e9rience r\u00e9v\u00e9lera quelles interactions entre g\u00e8nes restent anormales m\u00eame apr\u00e8s le traitement par FTI. Les donn\u00e9es permettront \u00e0 son \u00e9quipe de pr\u00e9dire les voies de signalisation qui peuvent \u00eatre responsables du HGPS et des sympt\u00f4mes persistants du HGPS signal\u00e9s dans les mod\u00e8les de souris trait\u00e9s par FTI, et fourniront une piste pour de nouveaux m\u00e9dicaments et traitements pour les patients atteints de HGPS.<\/p>\n<p>Le Dr Lieb est professeur associ\u00e9 au d\u00e9partement de biologie et au Carolina Center for Genome Sciences. Les projets de son laboratoire sont unis par l&#039;objectif scientifique de comprendre les relations entre l&#039;empaquetage de l&#039;ADN, le ciblage des facteurs de transcription et l&#039;expression des g\u00e8nes. Ils utilisent trois syst\u00e8mes biologiques : S. cerevisiae (levure de boulanger) pour \u00e9tudier les m\u00e9canismes mol\u00e9culaires de base ; C. elegans pour tester l&#039;importance de ces m\u00e9canismes dans un organisme multicellulaire simple ; et (3) des lign\u00e9es cellulaires et des \u00e9chantillons cliniques pour interroger directement la fonction de la chromatine dans le d\u00e9veloppement et la maladie humains. Les exp\u00e9riences seront men\u00e9es par le Dr Kohta Ikegami, chercheur postdoctoral, qui a suivi une formation d&#039;\u00e9tudiant dipl\u00f4m\u00e9 \u00e0 l&#039;Universit\u00e9 de Tokyo.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2009-2\u2033 module_id=\u201d2009-2\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Octobre 2009 :\u00a0<\/strong>\u00c0 Tom Misteli, PhD, National Cancer Institute, NIH, Bethesda, MD ; Identification de petites mol\u00e9cules modulatrices de l&#039;\u00e9pissage LMNA<\/p>\n<p>Le Dr Misteli et son \u00e9quipe d\u00e9veloppent de nouvelles strat\u00e9gies th\u00e9rapeutiques pour la prog\u00e9ria. Les travaux de son groupe visent \u00e0 interf\u00e9rer avec la production de la prot\u00e9ine prog\u00e9rine \u00e0 l&#039;aide d&#039;outils mol\u00e9culaires tr\u00e8s sp\u00e9cifiques et \u00e0 trouver de nouvelles petites mol\u00e9cules pour contrer les effets n\u00e9fastes de la prog\u00e9rine dans les cellules des patients. Ces efforts conduiront \u00e0 une compr\u00e9hension d\u00e9taill\u00e9e de la biologie cellulaire des cellules prog\u00e9ria et nous rapprocheront d&#039;une th\u00e9rapie mol\u00e9culaire pour la prog\u00e9ria.<\/p>\n<p>Le Dr Misteli est chercheur principal au National Cancer Institute, o\u00f9 il dirige le groupe de biologie cellulaire des g\u00e9nomes et l&#039;initiative de d\u00e9pistage cellulaire du NCI. Il est membre du centre d&#039;excellence en biologie chromosomique du NCI. Le Dr Misteli a \u00e9t\u00e9 le pionnier de la technologie permettant d&#039;analyser la fonction des g\u00e8nes dans les cellules vivantes et ses travaux ont fourni des informations fondamentales sur la fonction du g\u00e9nome. Le Dr Misteli a re\u00e7u de nombreux prix nationaux et internationaux pour ses travaux et il occupe de nombreuses fonctions consultatives et \u00e9ditoriales.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2009-3\u2033 module_id=\u201d2009-3\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Ao\u00fbt 2009 :\u00a0<\/strong>\u00e0 William L. Stanford, Ph. D., Universit\u00e9 de Toronto, Canada<br \/>\nCellules souches pluripotentes induites (iPSC) issues de fibroblastes de patients atteints de HGPS pour \u00e9lucider le m\u00e9canisme mol\u00e9culaire associ\u00e9 \u00e0 la diminution de la fonction vasculaire<\/p>\n<p>Les cellules iPS, ou cellules souches pluripotentes induites, sont des cellules qui ont commenc\u00e9 comme un type de cellule mature facilement obtenu et cultiv\u00e9 en laboratoire, et qui sont trait\u00e9es avec des \u00ab signaux \u00bb biochimiques qui signalent au m\u00e9canisme g\u00e9n\u00e9tique des cellules de les transformer en cellules souches immatures. Ces cellules souches re\u00e7oivent ensuite des \u00ab signaux \u00bb biochimiques suppl\u00e9mentaires pour m\u00fbrir \u00e0 nouveau, mais pas dans leur type cellulaire d&#039;origine. Par exemple, une cellule de peau (mature) peut d&#039;abord \u00eatre transform\u00e9e en cellule souche (immature) puis en cellule vasculaire (mature). Cette technologie de pointe est extr\u00eamement importante pour la recherche sur la prog\u00e9ria, o\u00f9 nous ne pouvons pas obtenir de cellules vivantes des vaisseaux sanguins, du c\u0153ur et des os d&#039;enfants atteints de prog\u00e9ria pour les \u00e9tudier. La capacit\u00e9 de prendre une cellule de peau de prog\u00e9ria, cultiv\u00e9e facilement \u00e0 la banque de cellules et de tissus PRF, et de cr\u00e9er une cellule de vaisseau sanguin de prog\u00e9ria, nous permettra d&#039;\u00e9tudier les maladies cardiaques li\u00e9es \u00e0 la prog\u00e9ria de mani\u00e8re totalement in\u00e9dite.<\/p>\n<p>Ces cellules seront utiles pour la mise en banque et la distribution aux membres de la communaut\u00e9 de recherche sur la Progeria pour des \u00e9tudes fondamentales et le d\u00e9veloppement de m\u00e9dicaments. Le Dr Stanford d\u00e9veloppera plusieurs cellules iPS de la Progeria pour mod\u00e9liser les cellules souches de la maladie vasculaire de la Progeria (VSMC), qui sont gravement \u00e9puis\u00e9es dans la Progeria.<\/p>\n<p>Le Dr Stanford est titulaire de la chaire de recherche du Canada en bio-ing\u00e9nierie des cellules souches et en g\u00e9nomique fonctionnelle, ainsi que professeur agr\u00e9g\u00e9 et directeur associ\u00e9 de l&#039;Institut des biomat\u00e9riaux et de l&#039;ing\u00e9nierie biom\u00e9dicale de l&#039;Universit\u00e9 de Toronto. Il est \u00e9galement codirecteur scientifique de l&#039;Ontario Human iPS Cell Facility. Son laboratoire se concentre sur la recherche fondamentale et appliqu\u00e9e en biologie des cellules souches, l&#039;ing\u00e9nierie tissulaire et la mod\u00e9lisation des maladies humaines \u00e0 l&#039;aide de la mutagen\u00e8se de la souris et de cellules iPS sp\u00e9cifiques au patient.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2009-4\u2033 module_id=\u201d2009-4\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Juillet 2009 :\u00a0<\/strong>\u00e0 Jakub Tolar, Universit\u00e9 du Minnesota, Minneapolis, MN<br \/>\nCorrection des cellules pluripotentes induites par la prog\u00e9ria humaine par recombinaison homologue<\/p>\n<p>Le laboratoire du Dr Tolar a montr\u00e9 que la th\u00e9rapie cellulaire allog\u00e9nique avec des cellules souches m\u00e9senchymateuses peut prolonger la survie dans le mod\u00e8le murin de Progeria, ce qui sugg\u00e8re que la th\u00e9rapie cellulaire peut \u00eatre b\u00e9n\u00e9fique pour les enfants atteints de Progeria. Cependant, les enfants pr\u00e9sentent une r\u00e9paration anormale de l&#039;ADN et, par cons\u00e9quent, on s&#039;attend \u00e0 ce qu&#039;ils subissent des toxicit\u00e9s importantes avec la chimioradioth\u00e9rapie n\u00e9cessaire \u00e0 la greffe de cellules provenant de donneurs non apparent\u00e9s. Par cons\u00e9quent, le Dr Tolar limitera cette toxicit\u00e9 en d\u00e9veloppant des cellules g\u00e9n\u00e9tiquement corrig\u00e9es \u00e0 partir des enfants Progeria eux-m\u00eames, en combinant le nouveau concept de cellules iPS provenant de patients Progeria avec la technologie \u00e9mergente de correction g\u00e9n\u00e9tique m\u00e9di\u00e9e par les nucl\u00e9ases \u00e0 doigt de zinc. De cette mani\u00e8re, il vise \u00e0 \u00e9tablir une plate-forme pour la traduction clinique d&#039;une th\u00e9rapie g\u00e9nique \u00e0 base de cellules souches plus s\u00fbre avec des types de cellules prog\u00e9nitrices de cellules iPS comme traitement d\u00e9finitif pour les enfants atteints de Progeria.<\/p>\n<p>Le Dr Tolar est professeur adjoint et m\u00e9decin traitant \u00e0 l&#039;Universit\u00e9 du Minnesota dans les divisions d&#039;h\u00e9matologie-oncologie p\u00e9diatrique et de transplantation de sang et de moelle osseuse p\u00e9diatrique. Les recherches du Dr Tolar portent sur l&#039;utilisation de cellules souches d\u00e9riv\u00e9es de la moelle osseuse et sur la th\u00e9rapie g\u00e9nique pour corriger les maladies g\u00e9n\u00e9tiques et am\u00e9liorer les r\u00e9sultats des transplantations de sang et de moelle osseuse.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2008-1\u2033 module_id=\u201d2008-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Septembre 2008 (date de d\u00e9but janvier 2009) :\u00a0<\/strong>\u00c0 Kris Noel Dahl, Ph. D., Universit\u00e9 Carnegie Mellon, Pittsburgh, Pennsylvanie<br \/>\n\u00ab Quantification du recrutement de la prog\u00e9rine dans les membranes \u00bb<\/p>\n<p>Le syndrome de Hutchinson-Gilford-Progeria (HGPS) r\u00e9sulte d&#039;une association anormale d&#039;une forme mutante d&#039;une prot\u00e9ine structurale de la lamine nucl\u00e9aire, la prog\u00e9rine, avec la membrane nucl\u00e9aire. Cependant, la nature de cette association accrue n&#039;a pas \u00e9t\u00e9 d\u00e9termin\u00e9e. Dans ce projet, le Dr Dahl et ses collaborateurs quantifieront les diff\u00e9rences d&#039;association membranaire de la lamine A normale et de la prog\u00e9rine en utilisant des prot\u00e9ines et des membranes purifi\u00e9es. Gr\u00e2ce \u00e0 ce syst\u00e8me, ils peuvent quantifier avec pr\u00e9cision la force de l&#039;interaction prot\u00e9ine-membrane, d\u00e9terminer les changements physiques que la membrane subit au contact de la prot\u00e9ine et examiner l&#039;orientation des prot\u00e9ines \u00e0 l&#039;interface. De plus, ce syst\u00e8me purifi\u00e9 leur permettra de manipuler diff\u00e9rentes variables telles que la composition de la membrane et la charge de la solution. Certaines des hypoth\u00e8ses \u00e0 examiner sont le r\u00f4le de la queue lipidique et du groupe de charge retenu sur la prog\u00e9rine par rapport \u00e0 la lamine A native et les effets sur l&#039;interaction membranaire.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/dahl.jpg\" alt=\"\" width=\"100\" height=\"133\" align=\"left\" hspace=\"3\" vspace=\"3\" \/>Le professeur Kris Noel Dahl est professeur adjoint aux d\u00e9partements de g\u00e9nie chimique et de g\u00e9nie biom\u00e9dical de l&#039;universit\u00e9 Carnegie Mellon. Elle a obtenu son doctorat en g\u00e9nie chimique \u00e0 l&#039;universit\u00e9 de Pennsylvanie et a effectu\u00e9 un stage postdoctoral au d\u00e9partement de biologie cellulaire de la facult\u00e9 de m\u00e9decine Johns Hopkins. Le groupe du Dr Dahl se concentre sur les propri\u00e9t\u00e9s m\u00e9caniques du noyau, du niveau mol\u00e9culaire au niveau multicellulaire. Le syndrome de Heidegger-Hyperion-Phosphorus est l&#039;un des nombreux types de maladies dans lesquels les mutations et la r\u00e9organisation mol\u00e9culaire conduisent \u00e0 des propri\u00e9t\u00e9s m\u00e9caniques nucl\u00e9aires uniques.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2008-2\u2033 module_id=\u201d2008-2\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Janvier 2008 :\u00a0<\/strong>\u00c0 Bryce M. Paschal, Ph. D., Facult\u00e9 de m\u00e9decine de l&#039;Universit\u00e9 de Virginie, Charlottesville, Virginie<br \/>\nTransport nucl\u00e9aire dans le syndrome de Hutchinson-Guilford<\/p>\n<p>En tant que composant principal de la lame nucl\u00e9aire, la lamine A contribue \u00e0 la plasticit\u00e9 structurelle de la membrane de l&#039;enveloppe nucl\u00e9aire, fournit des sites de fixation pour la chromatine et organise les complexes de pores nucl\u00e9aires dans la membrane. Compte tenu de cette disposition, nous \u00e9tudions comment les d\u00e9fauts de la lame nucl\u00e9aire observ\u00e9s dans le syndrome de Hutchinson-Guilford Progeria (HGPS) affectent la structure et la fonction du complexe de pores nucl\u00e9aires. Ces \u00e9tudes sont con\u00e7ues pour fournir un aper\u00e7u de la mani\u00e8re dont les changements dans l&#039;architecture nucl\u00e9aire contribuent aux changements dans l&#039;expression des g\u00e8nes dans le HGPS par le biais de m\u00e9canismes bas\u00e9s sur le transport.<\/p>\n<p>Le Dr Paschal est professeur associ\u00e9 de biochimie et de g\u00e9n\u00e9tique mol\u00e9culaire \u00e0 la facult\u00e9 de m\u00e9decine de l&#039;universit\u00e9 de Virginie, o\u00f9 il est membre du Centre de signalisation cellulaire et du Centre du cancer de l&#039;UVA. Le Dr Paschal s&#039;int\u00e9resse depuis longtemps aux voies responsables du transport intracellulaire.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2007-1\u2033 module_id=\u201d2007-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Octobre 2007 :\u00a0<\/strong>\u00c0 Michael A. Gimbrone, Jr., MD, en collaboration avec Guillermo Garcia-Cardena, Ph.D. et Belinda Yap, Ph.D., Center for Excellence in Vascular Biology, Brigham and Women&#039;s Hospital, Boston, MA<\/p>\n<p>\u00ab Dysfonctionnement endoth\u00e9lial et pathobiologie de l\u2019ath\u00e9roscl\u00e9rose acc\u00e9l\u00e9r\u00e9e dans le syndrome de Hutchinson-Gilford Progeria \u00bb<\/p>\n<p>Le syndrome de Hutchinson-Gilford Progeria (HGPS) affecte de multiples syst\u00e8mes organiques de diverses mani\u00e8res, mais ses manifestations les plus graves se situent peut-\u00eatre au niveau du syst\u00e8me cardiovasculaire, o\u00f9 il entra\u00eene une forme d&#039;ath\u00e9roscl\u00e9rose inhabituellement grave et acc\u00e9l\u00e9r\u00e9e, entra\u00eenant des crises cardiaques ou des accidents vasculaires c\u00e9r\u00e9braux mortels \u00e0 un \u00e2ge pr\u00e9coce. Le c\u0153ur et les vaisseaux sanguins sont tapiss\u00e9s d&#039;une membrane transparente, \u00e9paisse comme une cellule unique, compos\u00e9e de cellules endoth\u00e9liales vasculaires (EC), qui forment normalement le contenant naturel du sang ; les changements pathologiques de cette paroi vitale, collectivement appel\u00e9s \u00ab dysfonctionnement endoth\u00e9lial \u00bb, sont d\u00e9sormais reconnus comme essentiels au d\u00e9veloppement de maladies vasculaires, telles que l&#039;ath\u00e9roscl\u00e9rose. Le but de nos \u00e9tudes propos\u00e9es est de d\u00e9terminer comment la prot\u00e9ine mutante prog\u00e9rine, qui s&#039;accumule dans les noyaux des cellules du HGPS, influence la structure et la fonction des EC, conduisant potentiellement \u00e0 un dysfonctionnement endoth\u00e9lial. Pour explorer cette question, nous avons cr\u00e9\u00e9 une\u00a0<em>in vitro<\/em>\u00a0Nous avons \u00e9tudi\u00e9 un syst\u00e8me mod\u00e8le dans lequel la prot\u00e9ine mutante prog\u00e9rine est exprim\u00e9e dans des cellules endoth\u00e9liales humaines cultiv\u00e9es et avons commenc\u00e9 \u00e0 explorer les cons\u00e9quences pathologiques en utilisant une combinaison d&#039;analyses g\u00e9nomiques \u00e0 haut d\u00e9bit et d&#039;\u00e9tudes de structure-fonction mol\u00e9culaire. Nos donn\u00e9es pr\u00e9liminaires indiquent que l&#039;accumulation de prog\u00e9rine dans les cellules endoth\u00e9liales humaines entra\u00eene des changements marqu\u00e9s dans leur structure nucl\u00e9aire et, surtout, diverses manifestations mol\u00e9culaires de dysfonctionnement endoth\u00e9lial. Ces derni\u00e8res incluent l&#039;expression de mol\u00e9cules d&#039;adh\u00e9sion des leucocytes et de m\u00e9diateurs solubles qui se sont av\u00e9r\u00e9s \u00eatre associ\u00e9s au d\u00e9veloppement de l&#039;ath\u00e9roscl\u00e9rose. Nos \u00e9tudes promettent d&#039;apporter des informations m\u00e9canistes sur les pathologies vasculaires du HGPS et, esp\u00e9rons-le, conduiront \u00e0 de nouvelles strat\u00e9gies pour son traitement efficace.<\/p>\n<p>Le Dr Gimbrone est professeur de pathologie \u00e0 la Harvard Medical School (HMS) et pr\u00e9sident du d\u00e9partement de pathologie au Brigham and Women&#039;s Hospital (BWH). Il est \u00e9galement directeur du Centre d&#039;excellence en biologie vasculaire du BWH. Il est membre \u00e9lu de la National Academy of Sciences (\u00c9tats-Unis), de l&#039;Institute of Medicine et de l&#039;American Academy of Arts and Sciences. Son laboratoire est consacr\u00e9 \u00e0 l&#039;\u00e9tude de l&#039;endoth\u00e9lium vasculaire et de son r\u00f4le dans les maladies cardiovasculaires telles que l&#039;ath\u00e9roscl\u00e9rose. Le Dr Garcia-Cardena est professeur adjoint de pathologie \u00e0 la HMS et directeur du laboratoire de biologie des syst\u00e8mes au Centre d&#039;excellence en biologie vasculaire. Le Dr Yap est chercheur postdoctoral dans le laboratoire du Dr Gimbrone.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2007-2\u2033 module_id=\u201d2007-2\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Mai 2007 :\u00a0<\/strong>\u00c0 Thomas N. Wight, Ph. D., Benaroya Research Institute, Seattle, Washington<br \/>\nUtilisation d&#039;un mod\u00e8le murin de HGPS pour d\u00e9finir l&#039;influence de l&#039;expression de Lamin AD50 sur la production de matrice extracellulaire vasculaire et le d\u00e9veloppement de maladies vasculaires.<\/p>\n<p>La matrice extracellulaire (ECM) est compos\u00e9e de mol\u00e9cules qui entourent les cellules et agissent \u00e0 la fois comme support structurel et comme moyen pour une cellule de communiquer avec ses voisines. Au cours du d\u00e9veloppement de l&#039;ath\u00e9roscl\u00e9rose, ces mol\u00e9cules changent et entra\u00eenent le d\u00e9veloppement de la plaque, un processus qui prend des d\u00e9cennies chez la plupart des humains. Dans le syndrome de Hutchinson Gilford Progeria (HGPS), ce processus est consid\u00e9rablement acc\u00e9l\u00e9r\u00e9 et les changements sp\u00e9cifiques de la MEC ne sont pas enti\u00e8rement compris. Nous proposons donc d&#039;\u00e9tudier l&#039;effet du g\u00e8ne HGPS sur les changements d&#039;un groupe de mol\u00e9cules de la MEC, appel\u00e9es prot\u00e9oglycanes, qui sont connues pour jouer un r\u00f4le important dans le d\u00e9veloppement de la plaque ath\u00e9roscl\u00e9reuse. Pour ce faire, nous \u00e9tudierons un mod\u00e8le murin de HGPS d\u00e9velopp\u00e9 dans le laboratoire du Dr Francis Collins au NIH, qui d\u00e9veloppe une maladie vasculaire. Nos pr\u00e9c\u00e9dentes recherches utilisant cette souris ont montr\u00e9 une accumulation d&#039;une MEC riche en prot\u00e9oglycanes dans les r\u00e9gions malades des principales art\u00e8res. En plus d\u2019\u00e9tudier les prot\u00e9oglycanes dans les vaisseaux de ces souris nourries avec un r\u00e9gime riche en graisses, nous pr\u00e9l\u00e8verons \u00e9galement des cellules des vaisseaux pour les cultiver dans des bo\u00eetes de Petri, ce qui nous permettra d\u2019examiner de plus pr\u00e8s l\u2019effet sp\u00e9cifique du g\u00e8ne HGPS sur la matrice extracellulaire des cellules musculaires lisses vasculaires. Ingrid Harten, doctorante au d\u00e9partement de pathologie de l\u2019universit\u00e9 de Washington, travaillera avec le Dr Wight sur ce projet. Ces \u00e9tudes aideront \u00e0 identifier les voies possibles par lesquelles la forme mutante de la lamine A trouv\u00e9e dans le HGPS peut r\u00e9guler l\u2019expression des prot\u00e9oglycanes de mani\u00e8re \u00e0 conduire au d\u00e9veloppement d\u2019une ath\u00e9roscl\u00e9rose acc\u00e9l\u00e9r\u00e9e chez les enfants atteints du HGPS.<\/p>\n<p>Le Dr Wight est chercheur au Benaroya Research Institute de Virginia Mason et professeur affili\u00e9 de pathologie \u00e0 l&#039;Universit\u00e9 de Washington, o\u00f9 il a \u00e9t\u00e9 professeur de 1988 \u00e0 2000. Il a obtenu son doctorat \u00e0 l&#039;Universit\u00e9 du New Hampshire en 1972. Il a \u00e9t\u00e9 laur\u00e9at d&#039;une bourse American Heart Established Investigatorship, a si\u00e9g\u00e9 dans des sections d&#039;\u00e9tude du NIH et de l&#039;AHA et fait actuellement partie du comit\u00e9 de r\u00e9daction de quatre revues scientifiques. Le programme de recherche du Dr Wight se concentre sur la biologie cellulaire et la pathologie du tissu conjonctif. Ses int\u00e9r\u00eats sp\u00e9cifiques incluent les interactions entre les cellules et la matrice extracellulaire, en mettant l&#039;accent sur le r\u00f4le des prot\u00e9oglycanes et des mol\u00e9cules associ\u00e9es dans la r\u00e9gulation du comportement cellulaire, en particulier en relation avec les maladies cardiovasculaires.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2007-3\u2033 module_id=\u201d2007-3\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Mars 2007 :\u00a0<\/strong>\u00c0 Jemima Barrowman, PhD, Johns Hopkins School of Medicine, Baltimore, MD ; M\u00e9canisme fondamental du traitement de la lamine A : pertinence pour le trouble du vieillissement HGPS<\/p>\n<p>Le HGPS est caus\u00e9 par une mutation du g\u00e8ne codant la lamine A. Normalement, la lamine A subit une s\u00e9rie transitoire de modifications biochimiques \u00e0 son extr\u00e9mit\u00e9 C-terminale, y compris l&#039;ajout d&#039;un lipide (farn\u00e9syl) et d&#039;un groupe carboxylm\u00e9thyle. Finalement, la queue C-terminale modifi\u00e9e est cliv\u00e9e pour g\u00e9n\u00e9rer la forme finale de la lamine A. La mutation qui cause le HGPS emp\u00eache le clivage de la queue, ce qui donne une forme de lamine A farn\u00e9syl\u00e9e et m\u00e9thyl\u00e9e de mani\u00e8re permanente appel\u00e9e prog\u00e9rine. Un certain nombre d&#039;\u00e9tudes sugg\u00e8rent que le blocage de l&#039;ajout du lipide farn\u00e9syl \u00e0 la lamine A par un m\u00e9dicament (inhibiteur de la farn\u00e9syltransf\u00e9rase ; FTI) pourrait fournir une strat\u00e9gie th\u00e9rapeutique pour la prog\u00e9ria. Dans cette proposition, nous \u00e9tudierons la possibilit\u00e9 que la r\u00e9tention permanente du groupe carboxylm\u00e9thyle puisse \u00e9galement contribuer aux effets cellulaires toxiques de la prog\u00e9rine. Si tel est le cas, les m\u00e9dicaments qui inhibent la m\u00e9thylation carboxyle pourraient \u00e9galement \u00eatre consid\u00e9r\u00e9s comme une option th\u00e9rapeutique potentielle pour la prog\u00e9ria. Nous \u00e9tudierons \u00e9galement la possibilit\u00e9 que la prog\u00e9rine puisse imiter la lamine B, un parent farn\u00e9syl\u00e9 en permanence de la lamine A, entrant ainsi en comp\u00e9tition pour les partenaires de liaison de la lamine B au niveau de la membrane nucl\u00e9aire.<\/p>\n<p>Le Dr Barrowman est chercheur postdoctoral au d\u00e9partement de biologie cellulaire de la facult\u00e9 de m\u00e9decine Johns Hopkins et travaille dans le laboratoire du Dr Michaelis. Le Dr Michaelis est professeur au d\u00e9partement de biologie cellulaire de la facult\u00e9 de m\u00e9decine Johns Hopkins et s&#039;int\u00e9resse depuis longtemps \u00e0 la machinerie cellulaire qui modifie les prot\u00e9ines farn\u00e9syl\u00e9es. Son laboratoire a apport\u00e9 d&#039;importantes contributions \u00e0 la documentation des avantages potentiels de l&#039;utilisation d&#039;inhibiteurs de la farn\u00e9syl transf\u00e9rase (FTI) pour inhiber les effets cellulaires toxiques de la prog\u00e9rine.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2006-1\u2033 module_id=\u201d2006-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Ao\u00fbt 2006 :\u00a0<\/strong>\u00c0 Zhongjun Zhou, PhD, Universit\u00e9 de Hong Kong, Chine<strong><br \/>\n<\/strong><em>Th\u00e9rapie par cellules souches pour le vieillissement pr\u00e9matur\u00e9 li\u00e9 \u00e0 la laminopathie<br \/>\n<\/em><br \/>\nLes cellules souches sont des cellules qui peuvent se renouveler et se diff\u00e9rencier en diff\u00e9rents types de cellules. Elles sont importantes car elles remplacent les cellules us\u00e9es du corps et maintiennent l&#039;int\u00e9grit\u00e9 fonctionnelle de notre corps. Les diff\u00e9rents tissus de notre corps sont rapidement renouvel\u00e9s par les cellules souches et il est courant que les cellules souches d\u00e9clinent chez les personnes \u00e2g\u00e9es. Nous \u00e9mettons l&#039;hypoth\u00e8se que le potentiel des cellules souches chez les patients atteints de HGPS est compromis et ne peut pas fournir suffisamment de nouvelles cellules pour le renouvellement de divers tissus, ce qui conduit donc \u00e0 des processus de vieillissement acc\u00e9l\u00e9r\u00e9s. Dans ce projet, le Dr Zhou utilisera un mod\u00e8le murin pour HGPS pour tester si le nombre et les fonctions des cellules souches chez les souris HGPS sont diminu\u00e9s et si les cellules souches (moelle osseuse) d\u00e9riv\u00e9es de souris saines sauveront les ph\u00e9notypes vieillissants chez les souris HGPS. Il \u00e9tudiera \u00e9galement comment les cellules souches sont affect\u00e9es dans le HGPS. Ce travail teste directement la faisabilit\u00e9 d&#039;une strat\u00e9gie th\u00e9rapeutique potentielle pour le vieillissement pr\u00e9matur\u00e9 bas\u00e9 sur la laminopathie.<\/p>\n<p>Le Dr Zhou est professeur associ\u00e9 au d\u00e9partement de biochimie et \u00e0 la facult\u00e9 de m\u00e9decine de l&#039;universit\u00e9 de Hong Kong et a obtenu son doctorat en biochimie m\u00e9dicale \u00e0 l&#039;institut Karolinska, o\u00f9 il a \u00e9galement effectu\u00e9 sa formation postdoctorale au d\u00e9partement de biochimie m\u00e9dicale et de biophysique de l&#039;institut. Le principal objectif de recherche du groupe HI est le m\u00e9canisme mol\u00e9culaire du vieillissement pr\u00e9matur\u00e9 bas\u00e9 sur la laminopathie. En collaboration avec des groupes en Espagne et en Su\u00e8de, ils ont cr\u00e9\u00e9 une souris d\u00e9ficiente en Zmpste24 pour servir de mod\u00e8le murin pour HGPS. Ils ont d\u00e9couvert que la pr\u00e9lamine A non trait\u00e9e et la pr\u00e9lamine A tronqu\u00e9e trouv\u00e9es dans HGPS compromettent le recrutement des prot\u00e9ines de r\u00e9ponse\/r\u00e9paration des points de contr\u00f4le de l&#039;ADN endommag\u00e9, conduisant ainsi \u00e0 une r\u00e9paration d\u00e9fectueuse de l&#039;ADN qui \u00e0 son tour contribue \u00e0 un vieillissement acc\u00e9l\u00e9r\u00e9. Actuellement, ils \u00e9tudient si les cellules souches sont affect\u00e9es dans HGPS et testent sur des souris si la transplantation de moelle osseuse pourrait sauver, au moins partiellement, les ph\u00e9notypes de vieillissement pr\u00e9matur\u00e9.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2006-2\u2033 module_id=\u201d2006-2\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Ao\u00fbt 2006 :\u00a0<\/strong>\u00c0 Michael Sinensky, Ph. D., Universit\u00e9 d&#039;\u00c9tat de l&#039;Est du Tennessee, Johnson City, TN\u00a0<em>Effet des FTI sur la structure et l&#039;activit\u00e9 de la prog\u00e9rine<\/em><\/p>\n<p>Le syndrome de Hutchinson-Gilford Progeria (HGPS) r\u00e9sulte d&#039;une nouvelle mutation du g\u00e8ne codant la prot\u00e9ine pr\u00e9lamine A. Normalement, la pr\u00e9lamine A subit une s\u00e9rie d&#039;alt\u00e9rations biochimiques qui lui permettent de former une partie d&#039;une structure du noyau appel\u00e9e lamina nucl\u00e9aire. La pr\u00e9lamine A mutante form\u00e9e dans le HGPS (appel\u00e9e prog\u00e9rine) est d\u00e9fectueuse dans la derni\u00e8re de ces alt\u00e9rations biochimiques conduisant \u00e0 l&#039;accumulation d&#039;une mol\u00e9cule interm\u00e9diaire portant un groupe lipidique appel\u00e9 farn\u00e9syle. Des compos\u00e9s, appel\u00e9s FTI, qui bloquent la formation de cette version lipidique de la prog\u00e9rine ont \u00e9t\u00e9 postul\u00e9s comme ayant une utilisation th\u00e9rapeutique dans le traitement du HGPS. Dans cette proposition, nous d\u00e9crivons les tests de l&#039;hypoth\u00e8se selon laquelle la prog\u00e9rine pr\u00e9sente des nouveaut\u00e9s dans sa structure mol\u00e9culaire qui sont secondaires \u00e0 l&#039;ajout de farn\u00e9syle, en particulier l&#039;ajout de phosphate. Cette hypoth\u00e8se sera test\u00e9e ainsi que les effets des FTI sur ces ajouts postul\u00e9s de phosphate<\/p>\n<p>Le Dr Sinensky est professeur et directeur du d\u00e9partement de biochimie et de biologie mol\u00e9culaire du Quillen College of Medicine de l&#039;East Tennessee State University. Entre 1987 et 1994, son laboratoire, alors situ\u00e9 au centre des sciences de la sant\u00e9 de l&#039;universit\u00e9 du Colorado, a d\u00e9montr\u00e9 que la farn\u00e9sylation de la pr\u00e9lamine A se produisait et constituait la premi\u00e8re \u00e9tape d&#039;une voie de maturation prot\u00e9olytique de la mol\u00e9cule. Ce travail est n\u00e9 des efforts visant \u00e0 comprendre le m\u00e9canisme de r\u00e9gulation de la biosynth\u00e8se du cholest\u00e9rol, qui a \u00e9galement constitu\u00e9 une partie importante de notre programme de recherche. Depuis son d\u00e9m\u00e9nagement au Tennessee en 1995, ses principaux int\u00e9r\u00eats de recherche ont port\u00e9 sur la reconstruction in vitro de la voie de traitement de la pr\u00e9lamine A.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2006-3\u2033 module_id=\u201d2006-3\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Juin 2006 :\u00a0<\/strong>\u00c0 Jan Lammerding, Ph. D., Brigham and Women&#039;s Hospital, Cambridge, Massachusetts<br \/>\n<em>Le r\u00f4le de la m\u00e9canique nucl\u00e9aire et de la m\u00e9canotransduction dans le syndrome de Hutchinson-Gilford Progeria et l&#039;effet du traitement par inhibiteur de la farn\u00e9syltransf\u00e9rase<\/em><\/p>\n<p>Le syndrome de Hutchinson-Gilford Progeria (HGPS) est caus\u00e9 par des mutations du g\u00e8ne codant la lamine A\/C. Le Dr Lammerding a r\u00e9cemment d\u00e9montr\u00e9 que les cellules d\u00e9pourvues de lamine A\/C sont m\u00e9caniquement plus fragiles et pr\u00e9sentent une mort cellulaire accrue et une signalisation cellulaire protectrice diminu\u00e9e en r\u00e9ponse \u00e0 une stimulation m\u00e9canique. Une sensibilit\u00e9 m\u00e9canique anormale en r\u00e9ponse au flux sanguin et \u00e0 la dilatation des vaisseaux sanguins pourrait rendre les vaisseaux sanguins plus sensibles \u00e0 l&#039;ath\u00e9roscl\u00e9rose, principale cause de d\u00e9c\u00e8s chez les patients atteints du HGPS. De plus, une sensibilit\u00e9 accrue au stress m\u00e9canique pourrait \u00e9galement contribuer aux anomalies osseuses et musculaires observ\u00e9es chez les patients atteints du HGPS. Dans le cadre de ce projet, le Dr Lammerding m\u00e8nera une s\u00e9rie d&#039;exp\u00e9riences pour \u00e9valuer si les cellules des patients atteints du syndrome de Hutchinson-Gilford Progeria sont plus sensibles aux dommages caus\u00e9s par la stimulation m\u00e9canique. En outre, les exp\u00e9riences du Dr Lammerding permettront de tester si le traitement avec des inhibiteurs de la farn\u00e9syl-transf\u00e9rase (FTI), un nouveau m\u00e9dicament prometteur pour le HGPS, peut inverser les d\u00e9ficiences m\u00e9caniques des cellules HGPS et ainsi conduire \u00e0 une inversion de certains ph\u00e9notypes de maladies sp\u00e9cifiques aux tissus.<\/p>\n<p>Le Dr Lammerding est charg\u00e9 de cours \u00e0 la Harvard Medical School au sein du d\u00e9partement de m\u00e9decine du Brigham and Women&#039;s Hospital. Ses domaines d&#039;int\u00e9r\u00eat comprennent la biom\u00e9canique subcellulaire et la r\u00e9ponse de signalisation cellulaire \u00e0 la stimulation m\u00e9canique. Il se concentre en particulier sur la fa\u00e7on dont les mutations dans les prot\u00e9ines de l&#039;enveloppe nucl\u00e9aire telles que la lamine peuvent rendre les cellules plus sensibles au stress m\u00e9canique et affecter leur signalisation de m\u00e9canotransduction. Les connaissances acquises gr\u00e2ce \u00e0 ces travaux peuvent conduire \u00e0 une meilleure compr\u00e9hension du m\u00e9canisme mol\u00e9culaire sous-jacent aux laminopathies, un groupe diversifi\u00e9 de maladies comprenant la dystrophie musculaire d&#039;Emery-Dreifuss, la HGPS et la lipodystrophie partielle familiale.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2006-4\u2033 module_id=\u201d2006-4\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<\/p>\n<p align=\"left\"><strong>Juin 2006 :\u00a0<\/strong>\u00c0 Tom Misteli, Ph. D., National Cancer Institute, NIH, Bethesda, MD<br \/>\n<em>Approches th\u00e9rapeutiques mol\u00e9culaires pour le syndrome de Heidegger par correction de l&#039;\u00e9pissage du pr\u00e9-ARNm<\/em><\/p>\n<p>Le Dr Misteli et son \u00e9quipe d\u00e9veloppent de nouvelles strat\u00e9gies th\u00e9rapeutiques pour la prog\u00e9ria. Les travaux de son groupe visent \u00e0 interf\u00e9rer avec la production de la prot\u00e9ine prog\u00e9rine \u00e0 l&#039;aide d&#039;outils mol\u00e9culaires tr\u00e8s sp\u00e9cifiques et \u00e0 trouver de nouvelles petites mol\u00e9cules pour contrer les effets n\u00e9fastes de la prot\u00e9ine prog\u00e9rine dans les cellules des patients. Ces efforts conduiront \u00e0 une compr\u00e9hension d\u00e9taill\u00e9e de la biologie cellulaire des cellules prog\u00e9ria et nous rapprocheront d&#039;une th\u00e9rapie mol\u00e9culaire pour la prog\u00e9ria.<\/p>\n<p>Le Dr Misteli est chercheur principal au National Cancer Institute, o\u00f9 il dirige le groupe de biologie cellulaire des g\u00e9nomes. Il est membre du Centre d&#039;excellence en biologie chromosomique du NCI. Le Dr Misteli a \u00e9t\u00e9 le pionnier de la technologie permettant d&#039;analyser la fonction des g\u00e8nes dans les cellules vivantes et ses travaux ont fourni des informations fondamentales sur la fonction du g\u00e9nome. Le Dr Misteli a re\u00e7u de nombreux prix nationaux et internationaux pour ses travaux et il occupe de nombreuses fonctions consultatives et \u00e9ditoriales.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2005-1\u2033 module_id=\u201d2005-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Juin 2005 :\u00a0<\/strong>\u00c0 Lucio Comai, PhD, Universit\u00e9 de Californie du Sud, Los Angeles, CA\u00a0<em>Analyse fonctionnelle du syndrome de Hutchinson-Gilford<\/em><\/p>\n<p>Le Dr Comai \u00e9met l\u2019hypoth\u00e8se que l\u2019expression de la prot\u00e9ine mutante prog\u00e9rine (\u00e0 l\u2019origine de la prog\u00e9ria) entra\u00eene un vieillissement pr\u00e9matur\u00e9 et des maladies cardiaques en raison de la composition et de la fonction alt\u00e9r\u00e9es des complexes contenant la lamine A dans le noyau. Pour tester cette hypoth\u00e8se, il cherchera \u00e0 identifier les facteurs cellulaires qui interagissent diff\u00e9remment avec la lamine A et la prog\u00e9rine. Ces \u00e9tudes fourniront des informations essentielles sur les d\u00e9fauts mol\u00e9culaires de la prog\u00e9ria, alors que nous travaillons au d\u00e9veloppement de traitements au niveau cellulaire.<\/p>\n<p>Le Dr Comai est professeur associ\u00e9 de microbiologie mol\u00e9culaire et d&#039;immunologie \u00e0 la facult\u00e9 de m\u00e9decine USC Keck et membre de l&#039;Institut de m\u00e9decine g\u00e9n\u00e9tique de la facult\u00e9 de m\u00e9decine Keck, du Norris Comprehensive Cancer Center et du Research Center for Liver Diseases.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2005-2\u2033 module_id=\u201d2005-2\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Juin 2005 :\u00a0<\/strong>\u00c0 Loren G. Fong, PhD, Universit\u00e9 de Californie, Los Angeles, CA<em>; De nouveaux mod\u00e8les de souris pour \u00e9tudier la cause du syndrome de Hutchinson-Gilford<\/em><\/p>\n<p>Depuis la d\u00e9couverte de la mutation du g\u00e8ne de la Prog\u00e9ria il y a plus de deux ans, des efforts ont \u00e9t\u00e9 d\u00e9ploy\u00e9s dans plusieurs laboratoires pour cr\u00e9er une souris produisant la \u00ab mauvaise \u00bb lamine A (prog\u00e9rine) produite par la Prog\u00e9ria. Le Dr Fong et ses coll\u00e8gues y sont parvenus et vont maintenant \u00e9tudier les effets de la prog\u00e9rine de souris sur la croissance et les propri\u00e9t\u00e9s m\u00e9taboliques des cellules, le d\u00e9veloppement de l\u2019ath\u00e9roscl\u00e9rose, les anomalies osseuses et la lipodystrophie chez l\u2019animal entier, et enfin pour v\u00e9rifier si certaines anomalies peuvent \u00eatre invers\u00e9es par des inhibiteurs de la farn\u00e9syltransf\u00e9rase, actuellement les principaux candidats au traitement de la Prog\u00e9ria.<\/p>\n<p>Le Dr Fong est professeur adjoint adjoint \u00e0 l&#039;UCLA et s&#039;est associ\u00e9 au Dr Stephen Young, b\u00e9n\u00e9ficiaire d&#039;une subvention PRF en mai 2005, pour s&#039;attaquer \u00e0 cet important probl\u00e8me scientifique et m\u00e9dical.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2005-3\u2033 module_id=\u201d2005-3\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Janvier 2005 :\u00a0<\/strong>Au Dr Karima Djabali, PhD, Columbia University, New York, NY\u00a0;\u00a0<em>D\u00e9finition des effets n\u00e9gatifs dominants de la prog\u00e9rine sur les fonctions nucl\u00e9aires dans les cellules HGPS<\/em><\/p>\n<p>Le Dr Djabali m\u00e8nera une s\u00e9rie d\u2019exp\u00e9riences fascinantes visant \u00e0 d\u00e9montrer la relation directe entre le d\u00e9faut g\u00e9n\u00e9tique du syndrome de Hutchinson Gilford Progeria et de nombreux partenaires de liaison importants afin de caract\u00e9riser la base biologique de la maladie de Progeria. Ce travail fournira les donn\u00e9es de base n\u00e9cessaires pour aboutir \u00e0 des traitements potentiels.<\/p>\n<p>Le Dr Djabali est professeure adjointe au d\u00e9partement de dermatologie de la facult\u00e9 de m\u00e9decine de l&#039;universit\u00e9 de Columbia. Elle a particip\u00e9 \u00e0 des \u00e9tudes de g\u00e9n\u00e9tique mol\u00e9culaire sur les maladies g\u00e9n\u00e9tiques et dans les domaines de la biologie mol\u00e9culaire, de la biologie cellulaire, de la biochimie et de la prot\u00e9omique.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2004-1\u2033 module_id=\u201d2004-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2004 :\u00a0<\/strong>\u00c0 Robert D. Goldman, PhD et Dale Shumaker, PhD, \u00c9cole de m\u00e9decine de l&#039;Universit\u00e9 Northwestern, Chicago, Illinois<br \/>\n<em>Les effets de la mutation majeure sur la fonction de la lamine A humaine dans la r\u00e9plication de l&#039;ADN<\/em><\/p>\n<p>Les docteurs Goldman et Shumaker cherchent \u00e0 d\u00e9terminer la base mol\u00e9culaire par laquelle les mutations du g\u00e8ne de la prog\u00e9ria alt\u00e8rent la fonction nucl\u00e9aire et provoquent les effets du vieillissement pr\u00e9matur\u00e9 observ\u00e9s chez les enfants atteints de prog\u00e9ria. Cela permettra de mettre en lumi\u00e8re les m\u00e9canismes de base responsables des troubles li\u00e9s \u00e0 l&#039;\u00e2ge chez les enfants, des informations essentielles pour d\u00e9terminer les moyens de lutter contre la progression de la maladie.<\/p>\n<p>Professeur et pr\u00e9sident du d\u00e9partement de biologie cellulaire et mol\u00e9culaire \u00e0 la facult\u00e9 de m\u00e9decine de l&#039;universit\u00e9 Northwestern, le Dr Goldman a ax\u00e9 ses recherches sur la dynamique des lamines nucl\u00e9aires au cours du cycle cellulaire, en examinant la relation entre leur structure et leur fonction. Il est membre du NIH du groupe Molecular Approaches to Cell Functions and Interactions et si\u00e8ge au conseil consultatif sur les cellules souches embryonnaires humaines de la Juvenile Diabetes Foundation. Il a travaill\u00e9 comme instructeur et directeur en biologie cellulaire et mol\u00e9culaire au Marine Biological Laboratory de Woods Hole, dans le Massachusetts.<\/p>\n<p>Le Dr Shumaker est chercheur postdoctoral en biologie cellulaire et mol\u00e9culaire \u00e0 Northwestern et travaille avec le Dr Goldman sur l&#039;\u00e9tude des lamines nucl\u00e9aires depuis 2001.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2004-2\u2033 module_id=\u201d2004-2\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Ao\u00fbt 2004 (Date de d\u00e9but janvier 2005) :\u00a0<\/strong>\u00c0 Stephen Young, Ph. D., pour son projet intitul\u00e9 \u00ab Exp\u00e9riences g\u00e9n\u00e9tiques sur des souris pour comprendre la prog\u00e9ria \u00bb.<br \/>\nL&#039;objectif de ce projet de recherche est d&#039;utiliser des mod\u00e8les de souris pour \u00e9tablir une base intellectuelle pour la conception de th\u00e9rapies appropri\u00e9es pour le syndrome de Hutchinson-Gilford Progeria caus\u00e9 par l&#039;accumulation d&#039;une pr\u00e9lamine A mutante (souvent appel\u00e9e \u00ab prog\u00e9rine \u00bb) dans les cellules. Le laboratoire du Dr Young cr\u00e9era un mod\u00e8le de souris de Progeria et utilisera ce mod\u00e8le pour comprendre comment le changement g\u00e9n\u00e9tique de Progeria conduit \u00e0 une maladie cardiaque. Comme le conclut le\u00a0<strong>Atelier BMT<\/strong>, l\u2019\u00e9tude des mod\u00e8les de souris est une \u00e9tape cruciale dans le processus de d\u00e9couverte de traitements et de rem\u00e8des contre la prog\u00e9ria. Le Dr Young \u00e9crit : \u00ab Au cours des derni\u00e8res ann\u00e9es, nous avons cr\u00e9\u00e9 plusieurs mod\u00e8les animaux pour explorer la biologie de la lamin A\/C\u2026 Nous sommes absolument convaincus que des analyses approfondies de ces mod\u00e8les de souris apporteront des informations pertinentes pour la conception de th\u00e9rapies pour le HGPS.<\/p>\n<p>Le Dr Young est chercheur principal aux instituts J. David Gladstone, professeur de m\u00e9decine \u00e0 l&#039;UCSF et cardiologue au San Francisco General Hospital. Le Dr Young dirigera et supervisera la r\u00e9alisation de toutes les \u00e9tudes propos\u00e9es. Le Dr Young a de l&#039;exp\u00e9rience dans l&#039;utilisation de souris g\u00e9n\u00e9tiquement modifi\u00e9es dans la recherche biom\u00e9dicale. Son groupe de recherche a g\u00e9n\u00e9r\u00e9 et examin\u00e9 plus de 50 lign\u00e9es de souris transg\u00e9niques et plus de 20 souris cibl\u00e9es par g\u00e8ne. Ces derni\u00e8res ann\u00e9es, le Dr Young a \u00e9tudi\u00e9 les modifications post-traductionnelles des prot\u00e9ines, et en particulier les \u00e9tapes de traitement post-isopr\u00e9nylation. Au cours des derni\u00e8res ann\u00e9es, son laboratoire a g\u00e9n\u00e9r\u00e9 des souris knockout pour la farn\u00e9syltransf\u00e9rase, Zmpste24, Icmt et Rce1, et la pr\u00e9nylcyst\u00e9ine lyase.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2004-3\u2033 module_id=\u201d2004-3\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Avril 2004 :\u00a0<\/strong>\u00c0 Monica Mallampalli, Ph. D., et Susan Michaelis, Ph. D. : \u00ab Structure, localisation et analyse ph\u00e9notypique de la prog\u00e9rine, la forme mutante de la pr\u00e9lamine A dans le HGPS \u00bb<br \/>\nCe projet vise \u00e0 d\u00e9finir la structure de la prog\u00e9rine (la prot\u00e9ine anormale du HGPS), \u00e0 d\u00e9velopper un syst\u00e8me de culture cellulaire qui leur permet d&#039;\u00e9tudier la localisation de la prog\u00e9rine et \u00e0 g\u00e9n\u00e9rer des anticorps et des aptam\u00e8res sp\u00e9cifiques \u00e0 la prog\u00e9rine pour l&#039;analyse de la fonction et de la distribution de la prog\u00e9rine dans les cellules et les tissus des patients atteints du HGPS. La compr\u00e9hension de la structure de la prog\u00e9rine et la d\u00e9termination de la mani\u00e8re dont la prog\u00e9rine donne naissance \u00e0 l&#039;\u00e9tat pathologique aideront \u00e0 r\u00e9v\u00e9ler le m\u00e9canisme mol\u00e9culaire du HGPS, facilitant ainsi les approches rationnelles pour le d\u00e9veloppement de traitements.<\/p>\n<p>Le Dr Mallampalli est chercheur postdoctoral au d\u00e9partement de biologie cellulaire de la facult\u00e9 de m\u00e9decine Johns Hopkins avec le Dr Michaelis, professeur de biophysique de biologie cellulaire \u00e0 la facult\u00e9 de m\u00e9decine Johns Hopkins.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2003-1\u2033 module_id=\u201d2003-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Septembre 2003 :\u00a0<\/strong>\u00c0 Thomas W. Glover, Ph.D. pour le projet intitul\u00e9 \u00ab R\u00f4le des mutations de la lamine A dans le syndrome de Hutchinson-Gilford prog\u00e9ria \u00bb<strong><br \/>\n<\/strong>Ce projet s\u2019int\u00e9resse \u00e0 la question de savoir pourquoi les mutations de la lamine A conduisent au ph\u00e9notype de la prog\u00e9ria. R\u00e9cemment, le g\u00e8ne responsable du syndrome de HGPS a \u00e9t\u00e9 identifi\u00e9 et le syndrome de HGPS a rejoint un groupe de syndromes \u2013 les laminopathies \u2013 qui pr\u00e9sentent tous un d\u00e9faut sous-jacent dans le g\u00e8ne de la lamine A\/C (LMNA). Pratiquement tous les patients atteints de HGPS pr\u00e9sentent la m\u00eame mutation cr\u00e9ant un site donneur d\u2019\u00e9pissage anormal dans l\u2019exon 11 du g\u00e8ne LMNA. Le r\u00e9sultat de l\u2019\u00e9pissage erron\u00e9 cr\u00e9e une prot\u00e9ine \u00e0 laquelle il manque 50 acides amin\u00e9s pr\u00e8s de l\u2019extr\u00e9mit\u00e9 C-terminale. La r\u00e9gion supprim\u00e9e comprend un site de clivage de la prot\u00e9ine qui supprime normalement 18 acides amin\u00e9s, y compris un site de farn\u00e9sylation de la bo\u00eete CAAX. Nos efforts de recherche se concentrent d\u00e9sormais sur l\u2019examen des effets de la mutation causale dans des mod\u00e8les de culture cellulaire afin de mieux comprendre la maladie et de travailler vers l\u2019objectif \u00e0 long terme de d\u00e9couvrir un rem\u00e8de. \u00c0 cette fin, nous \u00e9tudions l&#039;effet de l&#039;expression de la lamine A mutante sur une vari\u00e9t\u00e9 de ph\u00e9notypes cellulaires, notamment la localisation de la lamine A, la mort cellulaire, le cycle cellulaire et la morphologie nucl\u00e9aire. Ces exp\u00e9riences impliquent l&#039;expression de la lamine A mutante et normale \u00e0 partir de constructions d&#039;expression de mammif\u00e8res dans une vari\u00e9t\u00e9 de types de cellules, et la confirmation par l&#039;examen des effets de la prot\u00e9ine native dans les lign\u00e9es cellulaires HGPS. De plus, nous d\u00e9veloppons un mod\u00e8le in vitro d&#039;adipogen\u00e8se dans le HGPS, qui pourrait donner un aper\u00e7u de l&#039;absence de graisse sous-cutan\u00e9e et des ph\u00e9notypes associ\u00e9s observ\u00e9s chez les patients atteints de HGPS. Enfin, nous \u00e9mettons l&#039;hypoth\u00e8se qu&#039;il pourrait \u00eatre possible de corriger ou d&#039;am\u00e9liorer le ph\u00e9notype mutant en exposant les cellules \u00e0 des compos\u00e9s qui inhibent la farn\u00e9sylation. Nous avons obtenu une vari\u00e9t\u00e9 de ces inhibiteurs et nous \u00e9tudions actuellement les effets de ces compos\u00e9s sur les ph\u00e9notypes cellulaires HGPS.<\/p>\n<p>Le Dr Glover est professeur au d\u00e9partement de g\u00e9n\u00e9tique humaine de l&#039;Universit\u00e9 du Michigan et s&#039;int\u00e9resse aux bases mol\u00e9culaires des maladies g\u00e9n\u00e9tiques humaines et \u00e0 l&#039;instabilit\u00e9 chromosomique. Il est l&#039;auteur de plus de 120 publications de recherche et chapitres de livres. Son laboratoire a beaucoup travaill\u00e9 sur l&#039;instabilit\u00e9 chromosomique dans les sites fragiles et a identifi\u00e9 et clon\u00e9 un certain nombre de g\u00e8nes de maladies humaines, plus r\u00e9cemment un g\u00e8ne responsable du lymph\u0153d\u00e8me h\u00e9r\u00e9ditaire, et a collabor\u00e9 \u00e0 l&#039;identification du g\u00e8ne de la lamine A responsable de la prog\u00e9ria de Hutchinson-Gilford.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2003-2\u2033 module_id=\u201d2003-2\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2003 :\u00a0<\/strong>\u00c0 Joan Lemire,\u00a0<strong>Doctorat : \u00ab D\u00e9veloppement d\u2019un mod\u00e8le de cellule musculaire lisse pour l\u2019\u00e9tude du syndrome de Hutchinson-Gilford Progeria : l\u2019aggr\u00e9cane est-il un composant important du ph\u00e9notype ? \u00bb<\/strong><br \/>\nCe projet vise \u00e0 comprendre le m\u00e9canisme par lequel la prog\u00e9rine entra\u00eene des alt\u00e9rations des tissus conjonctifs et, plus important encore, des maladies cardiovasculaires. Les enfants atteints de HGPS meurent d&#039;infarctus du myocarde, d&#039;insuffisance cardiaque congestive et d&#039;accidents vasculaires c\u00e9r\u00e9braux. L&#039;aggr\u00e9cane est un composant du tissu conjonctif et est consid\u00e9rablement \u00e9lev\u00e9 dans les fibroblastes des patients atteints de HGPS. Le Dr Lemire \u00e9met l&#039;hypoth\u00e8se que cette surexpression d&#039;aggr\u00e9cane ne se limite pas aux fibroblastes et que les cellules musculaires lisses art\u00e9rielles produiront \u00e9galement de l&#039;aggr\u00e9cane, ce qui pourrait contribuer de mani\u00e8re significative \u00e0 ce r\u00e9tr\u00e9cissement des art\u00e8res dans le HGPS. Si cela s&#039;av\u00e8re exact, la pr\u00e9vention ou l&#039;inversion du r\u00e9tr\u00e9cissement luminal par la manipulation de l&#039;aggr\u00e9cane pourrait retarder l&#039;apparition des sympt\u00f4mes cardiovasculaires.<\/p>\n<p>Le Dr Lemire est professeur adjoint \u00e0 l&#039;Universit\u00e9 Tufts et a r\u00e9cemment obtenu une subvention financ\u00e9e par le NIH pour soutenir la recherche sur le r\u00f4le de la d\u00e9corine dans le HGPS.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2003-3\u2033 module_id=\u201d2003-3\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2003 :<\/strong>\u00a0\u00c0 W. Ted Brown, MD, PhD, FACMG : \u00ab Effets de mutation n\u00e9gatifs dominants de la prog\u00e9rine \u00bb<br \/>\nPour trouver un traitement potentiel pour le HGPS, il faut comprendre le m\u00e9canisme par lequel la forme mut\u00e9e de la prot\u00e9ine lamine A, la prog\u00e9rine, conduit \u00e0 la maladie. La prog\u00e9rine semble avoir un\u00a0<em>mutation dominante n\u00e9gative;<\/em>\u00a0Elle prend de nouvelles fonctions et produit des effets n\u00e9gatifs et ind\u00e9sirables sur les fonctions cellulaires. Le Dr Brown \u00e9met l&#039;hypoth\u00e8se que la prog\u00e9rine se lie \u00e0 une prot\u00e9ine nucl\u00e9aire cl\u00e9, \u00e0 laquelle la lamine A ne se lie normalement pas, et que cette liaison anormale provoque des effets n\u00e9fastes. Le projet se concentre sur la caract\u00e9risation de cette liaison inhabituelle pour aider \u00e0 expliquer comment la mutation conduit au HGPS.<\/p>\n<p>Le Dr Brown est pr\u00e9sident du d\u00e9partement de g\u00e9n\u00e9tique humaine et directeur de la clinique George A Jervis \u00e0 l&#039;Institut de recherche fondamentale de l&#039;\u00c9tat de New York. Il est un expert mondial de la prog\u00e9ria, ayant \u00e9tudi\u00e9 le syndrome au cours des 25 derni\u00e8res ann\u00e9es. Sa banque de cellules d&#039;un certain nombre de lign\u00e9es cellulaires de la prog\u00e9ria et ses \u00e9tudes ont contribu\u00e9 \u00e0 l&#039;identification \u00e9ventuelle de mutations LMNA dans la prog\u00e9ria.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2002-1\u2033 module_id=\u201d2002-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Mai 2002 :\u00a0<\/strong>Au professeur associ\u00e9 Anthony Weiss de l&#039;Universit\u00e9 de Sydney<br \/>\nTitre du projet : Marqueurs mol\u00e9culaires candidats pour le syndrome de Hutchinson-Gilford Progeria<\/p>\n<p>Description du projet : Un diagnostic pr\u00e9cis du syndrome de Hutchinson-Gilford Progeria (HGPS) n\u00e9cessite un marqueur fiable. Nous avons utilis\u00e9 la d\u00e9tection de gli\u00e8ne pour d\u00e9crire le gp200 et identifi\u00e9 des transcrits surexprim\u00e9s cl\u00e9s qui sont d&#039;excellents candidats pour les marqueurs HGPS dans les fibroblastes en culture. Ce projet d&#039;un an nous permettra d&#039;utiliser la prot\u00e9omique pour identifier le gp200 et les m\u00e9thodes de RT-PCR en temps r\u00e9el pour examiner un marqueur candidat transcrit de premier plan, hgpg200. Nous am\u00e9liorerons la sensibilit\u00e9 de notre test gp200 publi\u00e9, \u00e9largirons l&#039;utilit\u00e9 de l&#039;analyse de transcriptions sp\u00e9cifiques et d\u00e9velopperons un test sensible pour faciliter la d\u00e9tection des marqueurs.<\/p>\n<p>Ce travail est important pour les enfants atteints de HGPS. (1) Il contribuera \u00e0 un diagnostic pr\u00e9coce et pr\u00e9cis. (2) Ce projet marque la premi\u00e8re fois que cette combinaison de prot\u00e9omique et de microarrays\/outils RT-PCR en temps r\u00e9el est utilis\u00e9e pour explorer les caract\u00e9ristiques mol\u00e9culaires du HGPS. (3) Nous identifierons les mol\u00e9cules cl\u00e9s qui distinguent le HGPS. Leur identification nous fournira des informations sur la biologie mol\u00e9culaire et la biochimie du HGPS. (4) D&#039;ici la fin de la premi\u00e8re ann\u00e9e, nous esp\u00e9rons fournir un test qui pourra \u00eatre envisag\u00e9 de mani\u00e8re fiable, au-del\u00e0 de la subvention actuelle, dans de petits \u00e9chantillons de biopsie et des cellules buccales pr\u00e9lev\u00e9es par \u00e9couvillonnage doux.<\/p>\n<p>Fran\u00e7ais:Notre biographie : Tony Weiss est pr\u00e9sident fondateur du programme de biotechnologie mol\u00e9culaire de l&#039;universit\u00e9 de Sydney, professeur associ\u00e9 de biochimie \u00e0 l&#039;\u00e9cole de biosciences mol\u00e9culaires et microbiennes de l&#039;universit\u00e9 de Sydney, chercheur invit\u00e9 honoraire en g\u00e9n\u00e9tique mol\u00e9culaire et clinique au Royal Prince Alfred Hospital et professeur invit\u00e9 \u00e0 l&#039;universit\u00e9 nationale de Singapour. Tony a re\u00e7u le prix Roslyn Flora Goulston et un prix australien de recherche postdoctorale, puis a \u00e9t\u00e9 nomm\u00e9 boursier postdoctoral de l&#039;ARC, apr\u00e8s quoi il s&#039;est install\u00e9 aux \u00c9tats-Unis en tant que boursier international Fogarty du NIH. Il a re\u00e7u d&#039;autres r\u00e9compenses, notamment une bourse Fulbright \u00e0 l&#039;universit\u00e9 de Stanford, avant de retourner en Australie en tant que boursier postdoctoral du CSIRO pour occuper un poste de professeur \u00e0 l&#039;universit\u00e9 de Sydney. Il a \u00e9t\u00e9 deux fois boursier Thomas et Ethel Mary Ewing et a \u00e9t\u00e9 nomm\u00e9 boursier d&#039;\u00e9change de la Royal Society pour poursuivre des \u00e9tudes de recherche au LTK. Tony a \u00e9t\u00e9 r\u00e9compens\u00e9 par la Soci\u00e9t\u00e9 australienne de biochimie et de biologie mol\u00e9culaire pour ses contributions remarquables dans le domaine de la biochimie et de la biologie mol\u00e9culaire et a re\u00e7u la m\u00e9daille de biotechnologie Amersham Pharmacia. Il a \u00e9galement re\u00e7u le prix et la m\u00e9daille de recherche David Syme, qui sont d\u00e9cern\u00e9s pour le meilleur travail de recherche original en biologie, chimie, g\u00e9ologie ou physique, produit en Australie, au cours des deux ann\u00e9es pr\u00e9c\u00e9dentes.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2001-1\u2033 module_id=\u201d2001-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Janvier 2001 (Date de d\u00e9but juillet 2001) :\u00a0<\/strong>\u00c0 John M. Sedivy, PhD, Brown University, Providence, RI ; et Junko Oshima, MD, PhD, University of Washington, Seattle, WA, \u00ab Clonage du g\u00e8ne du syndrome de Hutchinson-Gilford Progeria par compl\u00e9mentation de cellules somatiques \u00bb<\/p>\n<p>L&#039;objectif du projet de recherche est d&#039;identifier le g\u00e8ne dont la mutation est responsable du syndrome de Hutchinson-Gilford Progeria (HGPS). Le g\u00e8ne d&#039;un autre syndrome prog\u00e9ro\u00efde, le syndrome de Werner, a r\u00e9cemment \u00e9t\u00e9 identifi\u00e9 gr\u00e2ce \u00e0 des \u00e9tudes g\u00e9n\u00e9tiques men\u00e9es aupr\u00e8s de plusieurs grandes familles atteintes. Malheureusement, cette approche ne peut pas \u00eatre utilis\u00e9e dans le cas du HGPS, car il n&#039;existe pas de familles avec des pedigrees \u00e9tendus de HGPS. Le Dr Sedivy et son collaborateur, le Dr Frank Rothman, ont plut\u00f4t propos\u00e9 d&#039;identifier le g\u00e8ne du HGPS par des \u00e9tudes g\u00e9n\u00e9tiques de cellules obtenues de patients atteints du HGPS. Cette approche tirera parti de deux d\u00e9veloppements r\u00e9cents en biotechnologie : d&#039;une part, les microarrays d&#039;ADNc ou d&#039;oligonucl\u00e9otides \u00e0 haute densit\u00e9 (commun\u00e9ment appel\u00e9s \u00ab puces \u00e0 g\u00e8nes \u00bb), qui permettent d&#039;\u00e9tudier de nombreux g\u00e8nes \u00e0 la fois ; et d&#039;autre part, les syst\u00e8mes de vecteurs r\u00e9troviraux, qui permettent de concevoir un transfert tr\u00e8s efficace de l&#039;information g\u00e9n\u00e9tique d&#039;une cellule \u00e0 l&#039;autre. Les chercheurs tenteront d\u2019abord d\u2019identifier les mod\u00e8les d\u2019expression g\u00e9n\u00e9tique qui diff\u00e9rencient les cellules HGPS des cellules normales, puis utiliseront la technologie du vecteur r\u00e9troviral pour rechercher le g\u00e8ne (ou les g\u00e8nes) dans les cellules normales qui peuvent \u00ab gu\u00e9rir \u00bb les cellules HGPS.<\/p>\n<p>John M. Sedivy est professeur de biologie et de m\u00e9decine au d\u00e9partement de biologie mol\u00e9culaire, de biologie cellulaire et de biochimie de l&#039;universit\u00e9 Brown. Apr\u00e8s avoir termin\u00e9 ses \u00e9tudes de premier cycle \u00e0 l&#039;universit\u00e9 de Toronto en 1978, il a obtenu son doctorat en microbiologie et g\u00e9n\u00e9tique mol\u00e9culaire en 1984 \u00e0 l&#039;universit\u00e9 Harvard. Apr\u00e8s quatre ann\u00e9es de formation postdoctorale en g\u00e9n\u00e9tique des cellules somatiques dans le laboratoire du laur\u00e9at du prix Nobel Philip Sharp au Massachusetts Institute of Technology, il a commenc\u00e9 sa carri\u00e8re de chercheur ind\u00e9pendant en 1988 \u00e0 la facult\u00e9 de l&#039;universit\u00e9 Yale. Il a \u00e9t\u00e9 nomm\u00e9 jeune chercheur pr\u00e9sidentiel en 1990 et a re\u00e7u le prix Andrew Mellon en 1991.<\/p>\n<p>Il a rejoint l&#039;Universit\u00e9 Brown en 1996, o\u00f9 il enseigne la g\u00e9n\u00e9tique et supervise un groupe de recherche travaillant sur la biologie fondamentale du cancer et les m\u00e9canismes du vieillissement des cellules et des tissus humains. Il a si\u00e9g\u00e9 et continue de si\u00e9ger \u00e0 de nombreux comit\u00e9s d&#039;\u00e9valuation par les pairs pour les National Institutes of Health et l&#039;American Cancer Society. Son laboratoire a \u00e9t\u00e9 continuellement financ\u00e9 par les National Institutes of Health et a maintenu un record de publications productives dans des revues \u00e0 comit\u00e9 de lecture. En 2000, John Sedivy a \u00e9t\u00e9 nomm\u00e9 directeur d\u00e9sign\u00e9 du Centre de g\u00e9n\u00e9tique et de g\u00e9nomique qui est actuellement en cours de cr\u00e9ation \u00e0 l&#039;Universit\u00e9 Brown.<\/p>\n<p><strong>Frank G. Rothman, Ph. D., co-chercheur<\/strong><\/p>\n<p>Frank G. Rothman est professeur de biologie et recteur \u00e9m\u00e9rite \u00e0 l&#039;universit\u00e9 Brown. Il a obtenu son doctorat en chimie \u00e0 l&#039;universit\u00e9 Harvard en 1955. De 1957 \u00e0 1961, apr\u00e8s deux ans de service dans l&#039;arm\u00e9e am\u00e9ricaine, il a \u00e9t\u00e9 chercheur postdoctoral et associ\u00e9 en g\u00e9n\u00e9tique mol\u00e9culaire au MIT. De 1961 jusqu&#039;\u00e0 sa retraite en 1997, il a fait partie de la facult\u00e9 de biologie de l&#039;universit\u00e9 Brown. Il a enseign\u00e9 la biochimie, la g\u00e9n\u00e9tique et la biologie mol\u00e9culaire \u00e0 tous les niveaux. Ses recherches sur l&#039;expression des g\u00e8nes dans les micro-organismes ont \u00e9t\u00e9 financ\u00e9es en permanence par la National Science Foundation de 1961 \u00e0 1984. Il a \u00e9t\u00e9 doyen de la facult\u00e9 de biologie de 1984 \u00e0 1990 et recteur de l&#039;universit\u00e9 de 1990 \u00e0 1995. \u00c0 la fin des ann\u00e9es 1980, il a men\u00e9 des recherches sur le vieillissement du ver rond, Caenorhabditis elegans. Il a enseign\u00e9 des cours sur la biologie du vieillissement en 1988, puis \u00e0 nouveau en 1996. En tant que professeur \u00e9m\u00e9rite, il a particip\u00e9 \u00e0 des \u00e9tudes collaboratives sur la biologie du vieillissement, en mettant l&#039;accent sur la prog\u00e9ria.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2001-2\u2033 module_id=\u201d2001-2\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>D\u00e9cembre 2001 :\u00a0<\/strong>(Date de d\u00e9but f\u00e9vrier 2002) : \u00c0 Thomas W. Glover, Ph.D.<br \/>\n\u00ab Maintien du g\u00e9nome dans le syndrome de Hutchinson-Gilford Progeria \u00bb<\/p>\n<p>L&#039;objectif ultime est de comprendre le d\u00e9faut fondamental responsable du HGPS. Dans ce projet, nous examinerons des aspects sp\u00e9cifiques de la maintenance du g\u00e9nome dans les cellules HGPS. Nous nous concentrerons sur trois domaines, la dynamique des t\u00e9lom\u00e8res, le taux de mutation spontan\u00e9e et les effets sp\u00e9cifiques de la r\u00e9paration de l&#039;ADN. Nous mesurerons quantitativement les taux de d\u00e9gradation des t\u00e9lom\u00e8res dans les fibroblastes HGPS en infectant les cellules avec un r\u00e9trovirus exprimant hTERT (sous-unit\u00e9 catalytique de la t\u00e9lom\u00e9rase), modifi\u00e9 pour permettre un contr\u00f4le strict de l&#039;expression de la t\u00e9lom\u00e9rase. De plus, la maintenance de l&#039;ADN sera examin\u00e9e pour d\u00e9terminer si le HGPS, comme de nombreux syndromes de vieillissement pr\u00e9matur\u00e9, implique un d\u00e9faut de r\u00e9paration ou de r\u00e9plication de l&#039;ADN. Les \u00e9tudes comprendront l&#039;examen des niveaux basaux de p53 dans les fibroblastes HGPS, la capacit\u00e9 des fibroblastes HGPS \u00e0 r\u00e9parer des l\u00e9sions sp\u00e9cifiques de l&#039;ADN \u00e0 l&#039;aide d&#039;anticorps sp\u00e9cifiques aux l\u00e9sions et l&#039;examen du taux de mutations spontan\u00e9es dans les fibroblastes HGPS. De nombreuses \u00e9tudes porteront sur des lign\u00e9es de fibroblastes immortalis\u00e9s par t\u00e9lom\u00e9rase, ce qui permettra de r\u00e9aliser des exp\u00e9riences sans mesurer les effets caus\u00e9s par la s\u00e9nescence pr\u00e9matur\u00e9e des fibroblastes HGPS. Les \u00e9tudes propos\u00e9es ont le potentiel d&#039;apporter des r\u00e9ponses concr\u00e8tes quant \u00e0 savoir si le d\u00e9faut sous-jacent du HGPS est d\u00fb \u00e0 un mauvais entretien du g\u00e9nome. L&#039;\u00e9lucidation des ph\u00e9notypes cellulaires associ\u00e9s au HGPS constituera un outil pr\u00e9cieux pour d\u00e9terminer les voies mol\u00e9culaires d\u00e9fectueuses et, en fin de compte, pour d\u00e9couvrir le ou les g\u00e8nes de la maladie.<\/p>\n<p>Thomas W. Glover, Ph.D. : Le Dr Glover est professeur aux d\u00e9partements de g\u00e9n\u00e9tique humaine et de p\u00e9diatrie de l&#039;Universit\u00e9 du Michigan, \u00e0 Ann Arbor, dans le Michigan. Ses recherches portent sur la g\u00e9n\u00e9tique mol\u00e9culaire des troubles g\u00e9n\u00e9tiques humains et sur les \u00e9tudes de l&#039;instabilit\u00e9 chromosomique et de la r\u00e9paration de l&#039;ADN. Il a r\u00e9ussi \u00e0 identifier ou \u00e0 cloner un certain nombre de g\u00e8nes de maladies humaines, notamment ceux du syndrome de Menkes, une forme courante du syndrome d&#039;Ehlers-Danlos, et du lymph\u0153d\u00e8me h\u00e9r\u00e9ditaire. Il a publi\u00e9 plus de 100 publications scientifiques \u00e9valu\u00e9es par des pairs et a b\u00e9n\u00e9fici\u00e9 d&#039;un soutien financier continu du NIH. Il a si\u00e9g\u00e9 \u00e0 plusieurs comit\u00e9s de r\u00e9daction et est examinateur de subventions pour la March of Dimes Birth Defects Foundation et les National Institutes of Health.<\/p>\n<p>Michael W. Glynn, MS, co-chercheur, est un \u00e9tudiant dipl\u00f4m\u00e9 en derni\u00e8re ann\u00e9e de doctorat dans le laboratoire du Dr Glover au d\u00e9partement de g\u00e9n\u00e9tique humaine de l&#039;universit\u00e9 du Michigan. Il a termin\u00e9 les qualifications requises pour la candidature et a termin\u00e9 tous les travaux de classe et les exigences d&#039;enseignement. Parmi les distinctions, citons le prix James V. Neel pour l&#039;excellence acad\u00e9mique d\u00e9cern\u00e9 par le d\u00e9partement de g\u00e9n\u00e9tique humaine. Il est l&#039;auteur de plusieurs articles, d&#039;un chapitre de livre et de deux brevets. Michael a obtenu une ma\u00eetrise en microbiologie de l&#039;universit\u00e9 du Connecticut. Il a ensuite supervis\u00e9 le laboratoire de diagnostic ADN de la facult\u00e9 de m\u00e9decine de Yale sous la direction du Dr Allen Bale.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d2000-1\u2033 module_id=\u201d2000-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Janvier 2000 :\u00a0<\/strong>\u00c0 l&#039;attention du Dr Leslie B. Gordon, Ph. D.<br \/>\n\u00ab Le r\u00f4le de l\u2019acide hyaluronique dans le syndrome de Hutchinson-Gilford prog\u00e9ria \u00bb<\/p>\n<p>Le Dr Gordon se concentre sur la seule diff\u00e9rence constante entre les patients atteints du syndrome de Hutchinson-Gilford Progeria (HGPS) et les enfants en bonne sant\u00e9 : les patients atteints du syndrome de Hutchinson-Gilford Progeria (HGPS) ont des taux beaucoup plus \u00e9lev\u00e9s d\u2019un compos\u00e9 particulier \u2013 l\u2019acide hyaluronique (AH) \u2013 dans leurs urines. L\u2019AH est n\u00e9cessaire \u00e0 la vie car il aide \u00e0 maintenir les tissus ensemble, mais une trop grande quantit\u00e9 peut \u00eatre n\u00e9faste. Les concentrations d\u2019AH augmentent chez les personnes \u00e2g\u00e9es et les plaques qui s\u2019accumulent dans les vaisseaux sanguins des personnes qui meurent d\u2019une maladie cardiaque sont impr\u00e9gn\u00e9es d\u2019AH. Les enfants atteints du syndrome de Hutchinson-Gilford Progeria ont ces m\u00eames plaques dans tout leur corps, et c\u2019est ce qui joue un r\u00f4le majeur dans les crises cardiaques et les accidents vasculaires c\u00e9r\u00e9braux. L\u2019id\u00e9e que l\u2019AH contribue aux maladies cardiaques n\u2019est pas nouvelle, mais les travaux dans ce domaine ont \u00e9t\u00e9 r\u00e9cemment encourag\u00e9s par de nouveaux outils analytiques. Dans ce domaine de recherche relativement inexplor\u00e9, le Dr Gordon tente de suivre les preuves jusqu\u2019\u00e0 leur source pour d\u00e9couvrir si la maladie s\u2019aggrave \u00e0 mesure que les niveaux d\u2019AH augmentent et pour \u00e9tablir si le produit chimique favorise effectivement la formation de plaques. Si un tel lien \u00e9tait confirm\u00e9, cela pourrait conduire \u00e0 des th\u00e9rapies qui combattraient \u00e0 la fois le syndrome de Hutchinson-Gilford-Progeria et les maladies cardiovasculaires en r\u00e9duisant les niveaux d\u2019acide hyaluronique. \u00ab Tout traitement qui aide ces enfants aidera tr\u00e8s probablement des millions de personnes atteintes de maladies cardiovasculaires et potentiellement d\u2019autres probl\u00e8mes associ\u00e9s au vieillissement \u00bb, affirme le Dr Gordon.<\/p>\n<p>Le Dr Leslie Beth Gordon est professeure en p\u00e9diatrie \u00e0 l&#039;h\u00f4pital pour enfants Hasbro de Providence, dans le Rhode Island, et chercheuse associ\u00e9e \u00e0 la facult\u00e9 de m\u00e9decine de l&#039;universit\u00e9 Tufts de Boston, dans le Massachusetts, o\u00f9 elle m\u00e8ne ses recherches sur le syndrome de Guillain-Barr\u00e9. Elle a termin\u00e9 le programme combin\u00e9 de m\u00e9decine et de doctorat \u00e0 la facult\u00e9 de m\u00e9decine de l&#039;universit\u00e9 Brown en 1998, o\u00f9 elle a obtenu la meilleure note dans la cat\u00e9gorie des meilleurs r\u00e9sultats du programme m\u00e9dical et est devenue membre de la Sigma Xi Honor Society. Avant cela, elle a obtenu sa ma\u00eetrise en sciences \u00e0 l&#039;universit\u00e9 Brown en 1991. Son baccalaur\u00e9at \u00e8s arts de l&#039;universit\u00e9 du New Hampshire lui a \u00e9t\u00e9 d\u00e9cern\u00e9 en 1986.<\/p>\n<p>Le Dr Gordon travaille dans le laboratoire du Dr Bryan P. Toole, professeur d&#039;anatomie \u00e0 la facult\u00e9 de m\u00e9decine de l&#039;universit\u00e9 Tufts. Les autres personnes qui participent au projet sont Ingrid Harten, MS, Margaret Conrad, RN, et Charlene Draleau, RN.<br \/>\n[\/et_pb_text][et_pb_text admin_label=\u201d1999-1\u2033 module_id=\u201d1999-1\u2033 _builder_version=\u201d4.16\u2033 custom_margin=\u201d20px||35px|\u201d z_index_tablet=\u201d500\u2033 global_colors_info=\u201d{}\u201d]<strong>Ao\u00fbt 1999 :\u00a0<\/strong>\u00c0 l&#039;attention du Dr Leslie B. Gordon, Ph. D.<br \/>\n\u00ab La physiopathologie de l\u2019art\u00e9rioscl\u00e9rose est li\u00e9e au syndrome de Hutchinson-Gilford Progeria \u00bb<br \/>\n[\/et_pb_text][\/et_pb_column_inner][\/et_pb_row_inner][\/et_pb_column][\/et_pb_section][et_pb_section fb_built=\u201d1\u2033 module_class=\u201dfooter\u201d _builder_version=\u201d4.21.0\u2033 background_color=\u201d#29327a\u201d custom_margin=\u201d-2px|||||\u201d custom_padding=\u201d0|0px|0|0px|false|false\u201d z_index_tablet=\u201d500\u2033 border_width_top=\u201d12px\u201d border_color_top=\u201d#00b2e2\u2033 global_module=\u201d133\u2033 locked=\u201doff\u201d global_colors_info=\u201d{}\u201d][et_pb_row column_structure=\u201d1_4,1_4,1_2\u2033 make_equal=\u201don\u201d module_class=\u201d et_pb_row_fullwidth\u201d _builder_version=\u201d4.16\u2033 width=\u201d89%\u201d width_tablet=\u201d80%\u201d width_phone=\u201d\u201d width_last_edited=\u201don|desktop\u201d max_width=\u201d89%\u201d max_width_tablet=\u201d80%\u201d max_width_phone=\u201d\u201d max_width_last_edited=\u201don|desktop\u201d z_index_tablet=\u201d500\u2033 make_fullwidth=\u201don\u201d width_unit=\u201doff\u201d custom_width_percent=\u201d100%\u201d global_colors_info=\u201d{}\u201d][et_pb_column type=\u201d1_4\u2033 _builder_version=\u201d4.16\u2033 custom_padding=\u201d|||\u201d global_colors_info=\u201d{}\u201d custom_padding__hover=\u201d|||\u201d][et_pb_cta button_url=\u201dhttps:\/\/lp.constantcontactpages.com\/sl\/88gWWwz\u201d button_text=\u201dS&#039;inscrire maintenant\u201d admin_label=\u201dS&#039;inscrire aux mises \u00e0 jour\u201d module_class=\u201dsign-btn\u201d _builder_version=\u201d4.27.4\u2033 header_font_size=\u201d25px\u201d background_color=\u201d#29327a\u201d animation_style=\u201dslide\u201d animation_direction=\u201dleft\u201d animation_intensity_slide=\u201d25%\u201d link_option_url=\u201dhttps:\/\/lp.constantcontactpages.com\/sl\/88gWWwz\u201d header_font_size_tablet=\u201d\u201d header_font_size_phone=\u201d30px\u201d header_font_size_last_edited=\u201don|desktop\u201d z_index_tablet=\u201d500\u2033 border_radii=\u201don|25px|25px|25px|25px\u201d global_colors_info=\u201d{}\u201d button_bg_color__hover_enabled=\u201don\u201d button_bg_color__hover=\u201d#8fd2ed\u201d button_border_color__hover_enabled=\u201don\u201d]<\/p>\n<h2>S&#039;inscrire<\/h2>\n<h2>pour notre<\/h2>\n<h2>Mises \u00e0 jour\u00a0!<\/h2>\n<p>[\/et_pb_cta][\/et_pb_column][et_pb_column type=\u201d1_4\u2033 _builder_version=\u201d4.16\u2033 custom_padding=\u201d|||\u201d global_colors_info=\u201d{}\u201d custom_padding__hover=\u201d|||\u201d][et_pb_cta button_url=\u201dhttps:\/\/progeriaresearch.donorsupport.co\/-\/XZHJVWZR\u201d button_text=\u201dFaites un don maintenant\u201d admin_label=\u201dEnsemble, nous trouverons le rem\u00e8de !\u201d module_class=\u201dsign-btn\u201d _builder_version=\u201d4.16\u2033 header_font_size=\u201d25px\u201d background_color=\u201d#29327a\u201d animation_style=\u201dslide\u201d animation_direction=\u201dleft\u201d animation_intensity_slide=\u201d25%\u201d header_font_size_tablet=\u201d\u201d header_font_size_phone=\u201d30px\u201d header_font_size_last_edited=\u201don|desktop\u201d body_font_size_tablet=\u201d\u201d body_font_size_phone=\u201d\u201d body_font_size_last_edited=\u201don|desktop\u201d z_index_tablet=\u201d500\u2033 border_radii=\u201don|25px|25px|25px|25px\u201d global_colors_info=\u201d{}\u201d button_bg_color__hover_enabled=\u201don\u201d bouton_bg_color__hover=\u201d#8fd2ed\u201d bouton_border_color__hover_enabled=\u201don\u201d]<\/p>\n<h2>Ensemble, nous<\/h2>\n<h2><em>VOLONT\u00c9<\/em><\/h2>\n<h2>trouve le rem\u00e8de !<\/h2>\n<p>[\/et_pb_cta][\/et_pb_column][et_pb_column type=\u201d1_2\u2033 _builder_version=\u201d4.16\u2033 custom_padding=\u201d|||\u201d global_colors_info=\u201d{}\u201d custom_padding__hover=\u201d|||\u201d][et_pb_image src=\u201dhttps:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2025\/05\/2025-strip-for-website-footer-no-years.png\u201d title_text=\u201dBande 2025 pour pied de page de site web sans ann\u00e9es\u201d _builder_version=\u201d4.27.4\u2033 _module_preset=\u201ddefault\u201d custom_margin=\u201d35px||||false|false\u201d global_colors_info=\u201d{}\u201d][\/et_pb_image][\/et_pb_column][\/et_pb_row][\/et_pb_section]<\/p>","protected":false},"excerpt":{"rendered":"<p>[et_pb_section fb_built=\u201d1\u2033 fullwidth=\u201don\u201d disabled_on=\u201doff|off|off\u201d _builder_version=\u201d4.16\u2033 border_width_bottom=\u201d55px\u201d border_color_bottom=\u201d#29327a\u201d locked=\u201doff\u201d global_colors_info=\u201d{}\u201d][et_pb_fullwidth_header _builder_version=\u201d4.16\u2033 title_font_size=\u201d55\u2033 background_color=\u201d#29327a\u201d background_image=\u201dhttps:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2020\/12\/Alexandra_1920x687.jpg\u201d background_position=\u201dcenter_left\u201d custom_padding=\u201d11.5vw||11.5vw|\u201d custom_padding_tablet=\u201d\u201d custom_padding_phone=\u201d|56px||\u201d custom_padding_last_edited=\u201dsur|bureau\u201d title_font_size_tablet=\u201d45px\u201d title_font_size_phone=\u201d40px\u201d title_font_size_last_edited=\u201dsur|t\u00e9l\u00e9phone\u201d z_index_tablet=\u201d500\u2033 custom_css_main_element=\u201dbackground-position: center 18% !important;\u201d global_colors_info=\u201d{}\u201d] Subventions financ\u00e9es [\/et_pb_fullwidth_header][\/et_pb_section][et_pb_section fb_built=\u201d1\u2033 use_custom_gutter=\u201don\u201d gutter_width=\u201d1\u2033 specialty=\u201don\u201d padding_left_1=\u201d35px\u201d padding_left_2=\u201d35px\u201d padding_2_tablet=\u201d|||0px\u201d padding_2_phone=\u201d|||0px\u201d padding_2_last_edited=\u201don|desktop\u201d module_class_1=\u201dsidebar-secondary-nav\u201d module_class=\u201dhandprint-bg\u201d _builder_version=\u201d4.16\u2033 background_image=\u201dhttps:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2019\/04\/blue-handprint-only.png\u201d parallax=\u201don\u201d parallax_method=\u201doff\u201d inner_width=\u201d100%\u201d inner_max_width=\u201d100%\u201d custom_padding=\u201d0|0px|54px|0px|false|false\u201d z_index_tablet=\u201d500\u2033 border_width_top=\u201d10px\u201d border_color_top=\u201d#8fd2ed\u201d use_custom_width=\u201don\u201d width_unit=\u201doff\u201d custom_width_percent=\u201d100%\u201d [\u2026]<\/p>","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"\t\t\t\t[vc_row][vc_column][vc_custom_heading text=\"Grants Funded\" font_container=\"tag:h1|text_align:center\" use_theme_fonts=\"yes\"][vc_column_text]<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/09.gif\" alt=\"\" width=\"160\" height=\"167\" align=\"left\" border=\"0\" \/>\r\n\r\nAs of April 2018, PRF has provided over $7.7 million to fund 71 grants for Progeria-related research projects performed in 18 states and 14 other countries! In our continuing effort to encourage researchers to work in this field, we solicit proposals worldwide and through our scientific workshops. All projects are carefully evaluated by our Medical Research Committee and Board of Directors and we strive to fund research targeted to help us reach our goal of developing treatments and the cure for Progeria.\r\n\r\n<strong>Grants We Have Funded and Biological Sketches of the Researchers<\/strong>\r\n<ul>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#DRA\" target=\"_blank\" rel=\"noopener noreferrer\"><b>November 2017:<\/b><\/a> to Dr. Richard K. Assoian, PhD, Professor, University of Pennsylvania, Philadelphia, PA.\u00a0 \u201cAnalysis and attenuation of arterial stiffness in HGPS: implications for lifespan.\u201d<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Finkel\" target=\"_blank\" rel=\"noopener noreferrer\"><b>September 2017 (start date October 2017):<\/b><\/a> To Dr. Toren Finkel MD\/PhD, Director, Aging Institute, Pittsburgh, PA. \u201cVascular autophagy and HGPS Progression.\u201d<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#JCBI\" target=\"_blank\" rel=\"noopener noreferrer\"><b>December 2016 (start date February 1, 2017):<\/b><\/a> To Juan Carlos Belmonte Izpisua, PhD, Professor, Gene Expression Laboratories at The <a title=\"Salk Institute for Biological Studies\" href=\"https:\/\/en.wikipedia.org\/wiki\/Salk_Institute_for_Biological_Studies\" target=\"_blank\" rel=\"noopener noreferrer\">Salk Institute for Biological Studies<\/a>, La Jolla, CA, USA. He is the former director and assisted in establishing the <a title=\"es:Centro de Medicina Regenerativa de Barcelona\" href=\"https:\/\/es.wikipedia.org\/wiki\/Centro_de_Medicina_Regenerativa_de_Barcelona\" target=\"_blank\" rel=\"noopener noreferrer\">Center for Regenerative Medicine in Barcelona<\/a>. He has a Ph.D. in Biochemistry and Pharmacology from The University of Bologna, Italy and from the University of Valencia, Spain. He is a postdoctoral fellow from the University of Marburg\u2019 European Molecular Biology Laboratory (EMBL), in Heidelberg, Germany and UCLA, USA. \u201cAmelioration of premature aging phenotypes in Hutchinson-Gilford Progeria Syndrome.\u201d<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#RVB\" target=\"_blank\" rel=\"noopener noreferrer\"><b>December 2016 (start date February 1, 2017):<\/b><\/a> To Ricardo Villa-Bellosta, PhD, Team Leader, \u00a0\u00a0Fundaci\u00f3n Jim\u00e9nez D\u00edaz University Hospital Health Research Institute (FIIS-FJD, Spain). \u201cTherapeutic strategies to recover the normal pyrophosphate homeostasis in HGPS.\u201d<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#ISaggio\" target=\"_blank\" rel=\"noopener noreferrer\"><b>December 2016 (start date February 1, 2017):<\/b><\/a> To Isabella Saggio, PhD, Associate Professor of Genetics and Gene Therapy, Sapienza University (Rome, Italy). \"The lamin-interacting telomeric protein AKTIP in HGPS.\"<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#TMisteli\" target=\"_blank\" rel=\"noopener noreferrer\"><b>December 2016 (start date March 1, 2017):<\/b><\/a> To Tom Misteli, PhD, NIH Distinguished Investigator and the Director of the Center for Cancer Research at the National Cancer Institute, NIH. \"In vivo testing of candidate HGPS therapeutics.\"<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Silvia\" target=\"_blank\" rel=\"noopener noreferrer\"><strong>August 2016 (start date January 1, 2017):<\/strong><\/a>\u00a0To Silvia Ortega-Guti\u00e9rrez, Universidad Complutense de Madrid, Spain: Associate Professor since 2013; Ram\u00f3n y Cajal Scholar, Organic Chemistry Dept., 2008-2012; PhD, 2004; Worked under the supervision of Prof. Mar\u00eda Luz L\u00f3pez-Rodr\u00edguez, Medicinal Chemistry Dept. Fulbright Scholar, Prof. Ben Cravatt\u2019s Lab, Chemical Biology and Proteomics, The Scripps Research Institute in California, USA; \u201cNew isoprenylcysteine carboxylmethyltransferase (ICMT) inhibitors for the treatment of progeria.<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#foisner\" target=\"_blank\" rel=\"noopener noreferrer\"><strong>July 2016 (start date October 1, 2016):<\/strong><\/a> \u00a0To Roland Foisner, PhD, Professor of Biochemistry, Medical University Vienna and Deputy Director, Max F. Perutz Laboratories, Vienna, Austria. Scientific coordinator, former European network project EURO-Laminopathies and Editor-in-Chief, journal Nucleus; \u201cContribution of endothelial cell dysfunction to cardiovascular disease in progeria and implications for diagnostic and therapeutic targets.\u201d<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Izpisua\" target=\"_blank\" rel=\"noopener noreferrer\"><b>December 2015 (start date January 1, 2016):<\/b><\/a> To\u00a0Juan Carlos Belmonte Izpisua, PhD, Professor, Gene Expression Laboratories at The Salk Institute for Biological Studies, La Jolla, CA, USA.\u00a0 \u201cThe use of novel technologies to identify and validate potential therapeutic compounds for the treatment of Hutchinson-Gilford Progeria Syndrome.\u201d<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Fahey\" target=\"_blank\" rel=\"noopener noreferrer\"><b>December 2015 (start date March 1, 2016): <\/b><\/a><b>\u00a0<\/b>To Jed William Fahey, Sc.D., Director, Cullman Chemoprotection Center, <i>Assistant Professor, <\/i>Johns Hopkins University, School of Medicine, Department of Medicine, Division of Clinical Pharmacology, Department of Pharmacology & Molecular Sciences; Bloomberg School of Public Health, Department of International Health, Center for Human Nutrition; \u201cThe capacity of plant-derived isothiocyanates to surpass the efficacy of sulforaphane, with reduced toxicity to Progeria cell lines.\u201d<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Bum-Joon\" target=\"_blank\" rel=\"noopener noreferrer\"><strong>June 2015 (start date July 1, 2015): <\/strong><\/a>To Bum-Joon Park, PhD, Chairperson and Professor of the Department of Molecular Biology, Pusan National University, Republic of Korea; \u201cImprovement of therapeutic effect of JH4, progerin-lamin A\/C binding inhibitor, against progeria syndrome.\u201d<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Cooke\" target=\"_blank\" rel=\"noopener noreferrer\"><strong>June 2015 (start date September 1, 2015): <\/strong><\/a>To John P. Cooke, MD, PhD, Joseph C. \u201cRusty\u201d Walter and Carole Walter Looke Presidential Distinguished Chair in Cardiovascular Disease Research, Chair and Full Member of the Department of Cardiovascular Sciences Houston Methodist Research Institute, Director of the Center for Cardiovascular Regeneration Houston Methodist DeBakey Heart<b> <\/b>and Vascular Center, Houston, TX; \u201cTelomerase Therapy for Progeria.\u201d<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#FCollins\" target=\"_blank\" rel=\"noopener noreferrer\"><strong>June 2015 (start date September 1, 2015): <\/strong><\/a>To Francis Collins, MD, PhD, Director of the National Institutes of Health (NIH\/NHGRI), Bethesda, MD; \u201cPost-doctoral Candidate Funding for HGPS Research.\u201d<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Lamming\" target=\"_blank\" rel=\"noopener noreferrer\"><strong>June 2015 (start date September 1, 2015): <\/strong><\/a>Dudley Lamming, PhD, Assistant Professor in the Department of Medicine at the University of Wisconsin-Madison, Co-Director of the UW Department of Medicine Mouse Metabolic Phenotyping Platform, Madison, WI;\u00a0 \u201cIntervention in Progeria by Restriction of Specific Dietary Amino Acids\u201d.\u201d<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#CCavadas\" target=\"_blank\" rel=\"noopener noreferrer\"><strong>June 2015 (start date September 1, 2015):<\/strong>\u00a0<\/a>To Cl\u00e1udia Cavadas, PhD, Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra Portugal; \u201cPeripheral NPY reverts HGPS phenotype: a study in human fibroblasts and mouse model\u201d<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#CFerreira\" target=\"_blank\" rel=\"noopener noreferrer\"><strong><b>December 2014 (start date April 1, 2015):\u00a0<\/b><\/strong><\/a>To C\u00e9lia Alexandra Ferreira de Oliveira Aveleira, PhD, Center for Neuroscience and Cell Biology (CNC) and Institute for Interdisciplinary Research (IIIUC), University of Coimbra Portugal; \u201cGhrelin: a novel therapeutic intervention to rescue the phenotype of Hutchinson\u2010Gilford Progeria Syndrome\u201d<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#JCobos\" target=\"_blank\" rel=\"noopener noreferrer\"><b>December 2014 (start date February 1, 2015):<\/b><\/a><b>\u00a0<\/b><\/strong>To Jes\u00fas V\u00e1zquez Cobos, PhD, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain; \u201cQuantitation of Farnesylated Progerin in Progeroid Mouse Tissues and Circulating Leukocytes from Hutchinson-Gilford Progeria Patients\u201d<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#MMoses\" target=\"_blank\" rel=\"noopener noreferrer\"><strong><b>December 2014 (start date February 1, 2015): <\/b><\/strong><\/a>To Marsha Moses, PhD, Boston Children\u2019s Hospital, Boston, MA; \u201cDiscovering Novel Non-Invasive Biomarkers for Hutchinson-Gilford Progeria Syndrome\u201d<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#JRabinowitz\" target=\"_blank\" rel=\"noopener noreferrer\"><strong><b>December 2014 (start date March 1, 2015): <\/b><\/strong><\/a>To Joseph Rabinowitz, PhD, Temple University School of Medicine, Philadelphia, PA; \u201cAdeno-associated virus mediated co-delivery of wild type lamin A and microRNA against progerin\u201d<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#July2014\"><strong>July 2014 (start date November 1, 2014):<\/strong><\/a> To Vicente Andr\u00e9s Garc\u00eda, PhD, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain; \u201cGeneration of a HGPS Knock-in Pig Model to Expedite the Developement of Effective Clinical Applications\u201d.<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#June2013Snyder\"><strong>June 2013 (start date September 1, 2013): <\/strong><\/a>To Dr. Brian Snyder, PhD, : Beth Israel Deaconess Medical Center, Boston, MA.; \u201cCharacterization of the Musculoskeletal, Craniofacial and Skin Phenotypes of the G608G Progeria Mouse Model\u201d.<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#goldman2013\"><strong>June 2013 (start date September 1, 2013): <\/strong><\/a>To Dr. Robert Goldman, PhD, : Northwestern University; \u201cNew Insights into the Role of Progerin in Cellular Pathology\u201d.<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#June2013Carroll\"><strong>June 2013 (start date September 1, 2013): <\/strong><\/a>To Dr. Christopher Carroll, PhD, : Yale University, New Haven, CT.; \u201cRegulation of progerin abundance by the inner nuclear membrane protein Man1\u201d.<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#June2013Ullman\"><strong>June 2013 (start date September 1, 2013): <\/strong><\/a>To Dr. Katharine Ullman,: University of Utah, Salt Lake City, UT; \"Elucidating how progerin impacts the role of Nup153 in the DNA damage response\u201d.<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#June2013Wilson\"><strong>June 2013 (start date September 1, 2013): <\/strong><\/a>To Dr. Katherine Wilson,: Johns Hopkins School of Medicine, Baltimore, MD; \u201cNatural expression of progerin and consequences of reduced lamin A tail O-GlcNAcylation\u201d.<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#June2013Kennedy\"><strong>June 2013 (start date September 1, 2013):<\/strong><\/a> To Dr. Brian Kennedy,: Buck Institute for Research on Aging, Novato, CA;\u00a0\u201cSmall Molecule Aging Intervention in Progeria\u201d.<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Dec2012Ferbeyre\">December 2012 (start date August 2013):<\/a> <\/strong>\u00a0To Dr. Gerardo Ferbeyre, PhD, University of Montreal, Montreal, Canada: \u201cControl of progerin clearance by defarnesylation and phosphorylation at serine 22\u201c<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Dec2012Misteli\"><strong>December 2012 (start date February 2013):<\/strong><\/a> To Dr. Thomas Misteli, PhD, National Cancer Institute NIH, Bethesda, MD: \"Small molecule discovery in HGPS\"<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Dec2012Djabali\"><strong>December 2012 (start date April or May 2013):<\/strong> <\/a>To Karima Djabali, PhD, Technical University of Munich, Munich, Germany: \"Progerin dynamics during cell cycle progression\"<strong>\r\n<\/strong><\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Sept2012TM\">September 2012:<\/a> <\/strong>To Tom Misteli, PhD, National Cancer Institute, NIH, Bethesda, MD; Technician Award<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#July2012\">July 2012 (start date September 1, 2012):<\/a> <\/strong>To Vicente Andr\u00e9s Garc\u00eda, PhD, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain; \u201cQuantification of farnesylated progerin and identification of genes that activate aberrant <em>LMNA<\/em> splicing in Hutchinson-Gilford Progeria Syndrome\u201d<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#July2012SB\">July 2012 (start date September 1, 2012):<\/a> <\/strong>To Dr. Samuel Benchimol, York University, Toronto, Canada: \u201cInvolvement of p53 in the premature senescence of HGPS\u201d<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#July2012TM\"><strong>July 2012:<\/strong> <\/a>To Tom Misteli, PhD, National Cancer Institute, NIH, Bethesda, MD; Specialty Award Amendment<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Dec2011Dechat\">December 2011 (start date March 1, 2012):<\/a> <\/strong>To Dr. Thomas Dechat, PhD, Medical University of Vienna, Austria; \u201cStable membrane association of progerin and implications for pRb signaling<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Dec2011\"><strong>December 2011 (start date March 1, 2012): <\/strong><\/a>To Maria Eriksson,PhD, Karolinska Institute, Sweden; Analyzing the possibility for Progeria disease reversal<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Dec2011feb1\">December 2011 (start date March 1, 2012):<\/a> <\/strong>To Colin L. Stewart D.Phil, Institute of Medical Biology, Singapore; \"Defining themolecular basis to vascular smooth muscle deterioration in Progeria<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Sept2011\"><strong>September 2011 (start date January 1, 2012):<\/strong><\/a> To Dr. Dylan Taatjes, University of Colorado, Boulder, CO: Comparative metabolic profiling of HGPS cells and evaluation of phenotypic changes upon modulation of key metabolites<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#June2011\"><strong>June 2011 (start date January 1, 2012):<\/strong><\/a> to Jan Lammerding, PhD, Cornell University\u2019s Weill Institute for Cell and Molecular Biology, Ithaca, NY; Vascular smooth muscle cell dysfunction in Hutchinson-Gilford Progeria Syndrome<strong>\u00a0<\/strong><\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Dec2010 NWU\">December 2010 (start date April 1, 2011):<\/a> <\/strong>To Robert D. Goldman, PhD, Northwestern University Medical School, Chicago, IL; A Role for B-type Lamins in Progeria<strong>\u00a0<\/strong><\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Dec2010 MGH\">December 2010:<\/a> <\/strong>To John Graziotto, PhD,\u00a0 Massachusetts General Hospital, Boston, MA; Clearance of Progerin Protein as Therapeutic Target in Hutchinson-Gilford Progeria Syndrome<strong>\r\n<\/strong><\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Dec2010TG\"><strong>December 2010 (Start date April 1, 2011):<\/strong><\/a> To Tom Glover PhD, U Michigan, Ann Arbor, MI; \u201cIdentifying Genes for Progeria and Premature Aging by Exome Sequencing\u201d<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Dec2010 TSU\">December 2010 (start date March 1, 2011):<\/a> <\/strong>To Yue Zou, PhD, East Tennessee State University, Johnson City, TN; Molecular Mechanisms of Genome Instability in HGPS<strong>\u00a0<\/strong><\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Dec2010 UofM\">December 2010 (start date January 1, 2011):<\/a> <\/strong>To Kan Cao, PhD, University of Maryland, College Park, MD; Rapamycin Reverses Cellular Phenotype and Enhanced Mutant Protein Clearance in Hutchinson Gilford Progeria Syndrome<strong>\u00a0<\/strong><\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#June10\">June 2010 (start date October 1, 2010):<\/a> <\/strong>To Evgeny Makarov, PhD, Brunel University, Uxbridge, United Kingdom; Identification of the LMNA Splicing Regulators by Comparative Proteomics of the Spliceosomal Complexes.<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Oct09path\">October 2009:<\/a><\/strong>\u00a0 to Jason D. Lieb, PhD, University of North Carolina, Chapel Hill NC;\u00a0 Interactions between genes and lamin A\/progerin: a window to understanding Progeria pathology and treatment<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Oct09splice\">October 2009:<\/a><\/strong> To Tom Misteli, PhD, National Cancer Institute, NIH, Bethesda, MD;\u00a0 Identification of small molecule modulators of LMNA splicing<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#aug09\">August 2009:<\/a><\/strong> to William L. Stanford, PhD, University of Toronto, Canada\r\nInduced-Pluripotent Stem Cells (iPSC) from HGPS patient fibroblasts to elucidate the molecular mechanism associated with diminishing vascular function<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#jul09\">July 2009:<\/a><\/strong> to Jakub Tolar, University of Minnesota, Minneapolis, MN;\r\nCorrection of human progeria induced pluripotent cells by homologous recombination<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Sept08\">September 2008 (start date January 2009):<\/a><\/strong> To Kris Noel Dahl, PhD, Carnegie Mellon University, Pittsburgh, PA;\r\n\u201cQuantification of progerin recruitment to membranes\u201d<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#oct07\"><strong>October 2007<\/strong>:<\/a> To Michael A. Gimbrone, Jr., MD, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA Endothelial Dysfunction and the Pathobiology of Accelerated Atherosclerosis in Hutchinson-Gilford Progeria Syndrome<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#jano8\"><strong>September 2007 (Start date January 2008):<\/strong><\/a> To Bryce M. Paschal, PhD, University of Virginia School of Medicine, Charlottesville, VA; Nuclear Transport in Hutchinson-Guilford Progeria Syndrome<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#May07\">May 2007:<\/a><\/strong> To Thomas N. Wight, PhD, Benaroya Research Institute, Seattle, WA; The use of a mouse model of HGPS to define the influence of Lamin AD50 expression on vascular extracellular matrix production and the development of vascular disease.<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#March07\">March 2007:<\/a><\/strong> To Jemima Barrowman, PhD, Johns Hopkins School of Medicine, Baltimore, MD; Fundamental Mechanism of Lamin A Processing: Relevance to the Aging Disorder HGPS<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#aug206\">August 2006:<\/a><\/strong> To Zhongjun Zhou, PhD, University of Hong Kong, China.\u00a0 Stem cell therapy of Laminopathy-based Premature Aging<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#aug06\">August 2006:<\/a><\/strong> To Michael Sinensky, PhD, East Tennessee State University, Johnson City, TN;\r\nEffect of FTIs\u2019 on the Structure and Activity of Progerin<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#jun06\">June 2006:<\/a><\/strong> To Jan Lammerding, PhD, Brigham and Women's Hospital, Cambridge, MA; The role of nuclear mechanics and mechanotransduction in Hutchinson-Gilford Progeria syndrome and the effect of farnesyltransferase inhibitor treatment<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#junn06\">June 2006:<\/a><\/strong>To Tom Misteli, PhD, National Cancer Institute, NIH, Bethesda, MD;\r\nMolecular Therapy Approaches for HGPS via correction of pre-mRNA Splicing<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#jun05\">June 2005:<\/a> <\/strong>To Lucio Comai, PhD, University of Southern California, Los Angeles, CA; Functional Analysis of Hutchinson-Gilford Progeria Syndrome<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#jun205\">June 2005:<\/a> <\/strong>To Loren G. Fong, PhD, University of California, Los Angeles, CA;\r\nNew Mouse Models to Study the Cause of Hutchinson-Gilford Progeria Syndrome<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#Jan05\">January 2005: <\/a><\/strong>To Dr. Karima Djabali, PhD, Columbia University, New York, NY; Defining progerin dominant negative effects on the nuclear functions in HGPS cells<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#dec04\">December 2004: <\/a><\/strong>To Robert D. Goldman, PhD and Dale Shumaker, PhD, Northwestern University Medical School, Chicago, Illinois\r\nThe Effects of the Major Mutation on Human Lamin A's Function in DNA Replication<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html##BMT\"><strong>August 2004 (Start date January 2005): <\/strong><\/a>To Stephen Young, PhD, UCLA, Los Angeles, CA; for his project entitled \"Genetic Experiments in Mice to Understand Progeria\".<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#A04\"><strong>April 2004:<\/strong><\/a> To Monica Mallampalli, Ph D, and Susan Michaelis, PhD, The Johns Hopkins School of Medicine, Baltimore, MD; \u201cStructure, Location and Phenotypic Analysis of Progerin, the mutant form of prelamin A in HGPS\u201d<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#D03\"><strong>December 2003:<\/strong><\/a> To Joan Lemire, PhD, Tufts University School of Medicine, Boston, MA; \u201cDeveloping a smooth muscle cell model for the study of Hutchinson-Gilford Progeria Syndrome: Is aggrecan a significant component of the phenotype?\u201d<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#D032\"><strong>December 2003:<\/strong><\/a> To W. Ted Brown, MD, PhD, FACMG, The Institute for Basic Research in Developmental Disabilities, Staten Island, NY: \u201cDominant Negative Mutation Effects of Progerin\u201d<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#7\">September 2003:<\/a><\/strong> To Thomas W. Glover, Ph.D., University of Michigan, \"\r\nRole of Lamin A Mutations in Hutchinson-Gilford Progeria Syndrome\"<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#5\">May 2002:<\/a><\/strong>\u00a0To Associate Professor Anthony Weiss at the University of Sydney, Australia, Title of project: Candidate Molecular Markers for Hutchinson-Gilford Progeria Syndrome<\/li>\r\n \t<li><strong><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#3\">January 2001 (Start date July 2001):<\/a><\/strong> To John M. Sedivy, PhD Brown University, Providence, RI; & Junko Oshima, MD, PhD, University of Washington, Seattle, WA, Cloning of the Gene for Hutchinson-Gilford Progeria Syndrome by Somatic Cell Complementation\"<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#4\"><strong>December 2001 (<\/strong><strong>Start date<\/strong><strong> February 2002):<\/strong><\/a> To Thomas W. Glover, Ph.D., University of Michigan, \"Genome Maintenance in Hutchinson-Gilford Progeria Syndrome\"<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#1\"><strong>January 2000:<\/strong><\/a>\u00a0To Leslie B. Gordon, MD, PhD, Tufts University School of Medicine , Boston, MA; \"The Role of Hyaluronic Acid in Hutchinson-Gilford Progeria Syndrome\"<\/li>\r\n \t<li><a href=\"https:\/\/www.progeriaresearch.org\/grants_funded.html#1\"><strong>August 1999:<\/strong><\/a> To Leslie B. Gordon, MD, PhD, Tufts University School of Medicine , Boston, MA; \"The Pathophysiology of Arterioscleros is in Hutchinson-Gilford Progeria Syndrome\"<\/li>\r\n<\/ul>\r\n\r\n<hr \/>\r\n\r\n<a id=\"DRA\"><\/a><strong>November 2017:\u00a0<\/strong>to Dr. Richard K. Assoian, PhD, Professor, University of Pennsylvania, Philadelphia, PA.\u00a0 \u201cAnalysis and attenuation of <img class=\"alignright wp-image-3637\" src=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2017\/03\/Assoian.jpg\" alt=\"\" width=\"150\" height=\"192\" \/>arterial stiffness in HGPS: implications for lifespan.\u201d\r\n\r\nDr. Assoian feels their research will investigate why HGPS arteries stiffen prematurely and whether premature arterial stiffening can be prevented, either by pharmacologic treatment or genetic modification of mice.\r\n\r\nDr. Richard Assoian received his training at Johns Hopkins University (B.A), the University of Chicago (PhD) and the National Institutes of Health (post-doctoral). He was on the faculties of Columbia University and the University of Miami before moving to the University of Pennsylvania in 1998. He is currently Professor of Pharmacology in the Department of Systems Pharmacology and Translational Therapeutics in the School of Medicine. Dr. Assoian's lab studies how changes in the stiffness of the arterial extracellular matrix affects the function of arterial smooth muscle cells. In this current study, his lab will use a Progeria mouse model to study the basis of and consequence of premature arterial stiffening in HGPS.<a id=\"Finkel\"><\/a>\r\n\r\n<hr \/>\r\n\r\n<strong>September 2017 (start date October 2017): <\/strong>To Dr. Toren Finkel MD\/PhD, Director, Aging Institute, Pittsburgh, PA. \u201cVascular autophagy and HGPS Progression.\u201d<strong><img class=\"size-full wp-image-3028 alignright\" src=\"https:\/\/www.progeriaresearch.org\/wp-content\/uploads\/2017\/03\/T_Finkel-2a.jpg\" alt=\"\" width=\"125\" height=\"181\" \/><\/strong>\r\n\r\nDr. Finkel is trying to understand why HGPS is a segmental progeria, namely, why it seems to effect certain tissues more than other tissues. He is particularly interested in why problems with blood vessels arise. It is believed that this segmental nature of the disease might be because the cell that helps make up blood vessels, the vascular smooth muscle cell, might respond slightly differently to progerin expression than other cell types. This difference has to do with another protein called p62, which is involved in the cellular process of autophagy. He believes that p62 behaves differently in smooth muscle cells compared to other cells (in smooth muscle cells it appears to localize in the cell nucleus) and that these differences might explain why the blood vessels have so many problems in HGPS. He also believes that medicine can be developed that effects p62 and that these drugs might be useful to treat HGPS patients.\r\n\r\nToren Finkel is the Director of the Aging Institute at the University of Pittsburgh\/UPMC and the G. Nicholas Beckwith III and Dorothy B. Beckwith Chair in Translational Medicine at the University of Pittsburgh Department of Medicine. He received his undergraduate degree in Physics and his MD and PhD degree from Harvard Medical School in 1986. Following a residency in Internal Medicine at the Massachusetts General Hospital, he completed a fellowship in Cardiology at Johns Hopkins Medical School. In 1992, he came to the NIH as an Investigator within the Intramural Research Program of the National Heart, Lung and Blood Institute (NHLBI). During his time at the NIH, he held various positions including Chief of the Cardiology Branch and Chief of the Center for Molecular Medicine within the NHLBI. He is a member of the American Society for Clinical Research (ASCR), the Association of American Physicians (AAP) and a Fellow of the American Association for the Advancement of Science (AAAS). He serves on numerous editorial boards including currently serving on the Board of Reviewing Editors for\u00a0<em>Science<\/em>. Although NIH Intramural Funds have primarily supported his work, his laboratory has received support as a Senior Scholar of the Ellison Medical Foundation and by the Leducq Foundation, where he currently serves as the US coordinator for a Transatlantic Network studying cardiac regeneration. His current research interests include the role of autophagy, reactive oxygen species and mitochondrial function in aging and age-related diseases.\r\n<a id=\"JCBI\"><\/a>\r\n\r\n<hr \/>\r\n\r\n<strong>December 2016 (start date February 1, 2017):<\/strong> To Juan Carlos Belmonte Izpisua, PhD, Professor, Gene Expression Laboratories at The <a title=\"Salk Institute for Biological Studies\" href=\"https:\/\/en.wikipedia.org\/wiki\/Salk_Institute_for_Biological_Studies\">Salk Institute for Biological Studies<\/a>, La Jolla, CA, USA. He is the former director and assisted in establishing the <a title=\"es:Centro de Medicina Regenerativa de Barcelona\" href=\"https:\/\/es.wikipedia.org\/wiki\/Centro_de_Medicina_Regenerativa_de_Barcelona\">Center for Regenerative Medicine in Barcelona<\/a>. He has a Ph.D. in Biochemistry and Pharmacology from The University of Bologna, Italy and from the University of Valencia, Spain. He is a postdoctoral fellow from the University of Marburg\u2019 European Molecular Biology Laboratory (EMBL), in Heidelberg, Germany and UCLA, USA. \u201cAmelioration of premature aging phenotypes in Hutchinson-Gilford Progeria Syndrome.\u201d\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/JuanCarlosIzpisuaBelmonte1.jpg\" width=\"125\" height=\"165\" \/>Cardiovascular alterations are the leading cause of death among Progeria patients. Dr. Izpisua Belmonte\u2019s laboratory has demonstrated that cellular reprogramming can rejuvenate cells from Progeria. His laboratory is now using cellular reprogramming to ameliorate aging phenotypes in mouse models of Progeria with special focus on the cardiovascular system. These discoveries could lead to the development of novel treatments for Progeria patients.\r\n\r\nDr. Izpisua Belmonte\u2019s area of research is focused on the understanding of stem cell biology,\u00a0organ and tissue development and regeneration. He has published over 350 articles in high\u00a0profile, internationally recognized, peer-reviewed journals and book chapters. He has received\u00a0several notable honors and awards, including the William Clinton Presidential Award, the Pew\u00a0Scholar Award, the National Science Foundation Creativity Award, the American Heart\u00a0Association Established Investigator Award, and the Roger Guillemin Nobel Chair for his\u00a0endeavors in these fields. Through the years his work has contributed to uncovering the role of\u00a0some homeobox genes during organ and tissue patterning and specification, as well as the\u00a0identification of the molecular mechanisms that determine how the different cell type precursors\u00a0of internal organs are organized spatially along the embryonic left right axis. His work is\u00a0contributing to give us a glimpse into the molecular basis implicated during organ regeneration\u00a0in higher vertebrates, the differentiation of human stem cells into various tissues as well as\u00a0aging and aging related diseases. The ultimate goal of his research is the development of new molecules and specific gene and cell based treatments to cure diseases affecting mankind.\r\n<a id=\"RVB\"><\/a>\r\n\r\n<hr \/>\r\n<p class=\"justifyleft\"><strong>December 2016 (start date February 1, 2017): <\/strong>To Ricardo Villa-Bellosta, PhD, Team Leader,\u00a0\u00a0 Fundaci\u00f3n Jim\u00e9nez D\u00edaz University Hospital Health Research Institute (FIIS-FJD, Spain). \u201cTherapeutic strategies to recover the normal pyrophosphate homeostasis in HGPS.\u201d<\/p>\r\n<b><img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/RicardoVillaBellosta.jpg\" width=\"125\" height=\"180\" \/><\/b>Like HGPS patients, Lmna<sup>G609G\/+<\/sup> mice exhibit excessive vascular calcification due to impaired capacity of the body to synthesize extracellular pyrophosphate (PPi). Because an imbalance between degradation and synthesis of extracellular PPi can also lead to pathological calcification of articular cartilage and other soft tissues, the systemic decrease in circulating PPi associated with progerin expression could explain several HGPS clinical manifestations, including vascular calcification, bone and joint abnormalities. Treatment with exogenous PPi reduced vascular calcification but did not increase the life span of Lmna<sup>G609G\/G609G<\/sup> mice. It is due to the rapid hydrolysis of exogenous PPi to the basal serum level, which reduce the time of action of PPi to prevent ectopic calcification in other soft tissues such as joints. Restoring the correct PPi homeostasis in Lmna<sup>G609G\/+<\/sup>mice using pharmacological inhibitors of the enzymes involved in extracellular pyrophosphate metabolism, could improve both quality of life and life span.\r\n\r\nRicardo Villa-Bellosta obtained his PhD degree in 2010 from the Zaragoza University (Spain). His doctoral work was focused on the role of phosphate transporters in vascular calcification, renal physiology and toxicokinetics of arsenic.\u00a0For his work he has received several awards including the Extraordinary Doctoral Award, the Spanish Royal Academy of Doctors Award and the Enrique Coris Research Award. He was a visiting researcher at the Emory University School of Medicine in Atlanta (USA) where he studied the extracellular pyrophosphate (ePPi) metabolism in the aortic wall. In 2012 he joined the Centro Nacional de Investigaciones Cardiovasculares (CNIC, Spain) as a Juan de la Cierva postdoctoral researcher focusing his work on the ePPi metabolism both in atheroma plaque calcification and in vascular calcification in HGPS mice. In 2015 he moved to the Fundaci\u00f3n Jim\u00e9nez D\u00edaz University Hospital Health Research Institute (FIIS-FJD, Spain) to study the phosphate\/pyrophosphate homeostasis in hemodialysis patients as a Sara Borrell postdoctoral researcher. In September 2015 he was granted with an \u201cI+D+I Young Researchers\u201d fellowship as a Team Leader in the FIIS-FJD to study the role of ePPi metabolism on vascular calcification in chronic kidney disease and diabetes.\r\n\r\n<hr \/>\r\n\r\n<strong>December 2016 (start date February 1, 2017):<\/strong> To Isabella Saggio, PhD, Associate Professor of Genetics and Gene Therapy, Sapienza University (Rome, Italy). \"The lamin-interacting telomeric protein AKTIP in HGPS.\"\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/saggio-photo-2016.jpg\" width=\"125\" height=\"136\" \/>The causative mutation of HGPS affects lamin A. AKTIP, a protein that we recently characterized, is is a lamin-interacting factor essential for cell survival, implicated in telomere and DNA metabolism. Four main observations link this new protein to HGPS: i) AKTIP impairment recapitulates HGPS characteristics in cells; ii) AKTIP impairment recapitulates HGPS characteristics in mice; iii) AKTIP interacts with lamins, and iv) AKTIP is altered in patient-derived HGPS cells. In our studies we postulate the hypothesis that an AKTIP complex acts as a checkpoint for challenging DNA replicative events. We expect that in HGPS this checkpoint is compromised, which, in turn, may contribute to the HGPS phenotype. We propose to extensively analyze AKTIP function in vitro and in mice. We expect that this research will give new insights into the connection between progerin and telomere dysfunction through AKTIP, along with information on the role of DNA replication impairment as a potential driver mechanism in progeria. Given that the knowledge of the determinants and driver mechanisms of HGPS etiology has not yet been fully acquired, we believe that studies on new lamin-interacting players, such as AKTIP, will be instrumental to dissect the mechanistic bases of HGPS and to open the path to novel therapeutic strategies.\r\n\r\nIsabella Saggio received her PhD in Genetics at Sapienza University (Rome, Italy). She worked in the Merck Research Institute for Molecular Biology (Rome Italy) from 1991 to 1994. From 1994 to 1997 she was EU postdoctoral fellow at IGR (Paris France). In 1998 she came back to Sapienza University, at first as a research assistant and then as an associate professor of Genetics and Gene Therapy. I.S. main research interests are gene therapy along with studies on telomeres and aging. I.S. has been member of the San Raffaele Science Park from 2003 to 2011, is part of CNR since 2003, of the Italian Network for Laminopathies since 2016. I.S. is the Sapienza representative in the Interuniversity Biotechnology Network in Italy, coordinates international activities at Sapienza and founded in 2016 a Master of Scientific Journalism to improve the relationships between researchers and public (<a href=\"https:\/\/www.mastersgp.it\/\">www.mastersgp.it<\/a>). I.S. activities are described on the site: <a href=\"https:\/\/www.saggiolab.com\/\">www.saggiolab.com<\/a>.\r\n\r\n<hr \/>\r\n\r\n<strong>December 2016 (start date March 1, 2017): <\/strong>To Tom Misteli, PhD, NIH Distinguished Investigator and the Director of the Center for Cancer Research at the National Cancer Institute, NIH. \"In vivo testing of candidate HGPS therapeutics.\"\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Misteliportrait-(1).jpg\" width=\"125\" height=\"146\" \/>Our goal is to test new potential progeria therapeutic agents in vivo. This highly collaborative project is based on the discovery in the laboratory of Tom Misteli of several candidate therapeutic agents, the development of a HGPS animal model in the laboratory of Carlos Lopez-Otin and the expertise of Alicia Rodriguez-Folgueras in testing of diverse compounds in an in-vivo setting.\r\n\r\nTom Misteli is an NIH Distinguished Investigator and the Director of the Center for Cancer Research at the National Cancer Institute, NIH. He is an internationally renowned cell biologist who pioneered the use of imaging approaches to study genomes and gene expression in living cells. His laboratory\u2019s interest is to uncover the fundamental principles of 3D genome organization and function and to apply this knowledge to the development of novel diagnostic and therapeutic strategies for cancer and aging. He obtained his PHD from the University of London, UK and performed post-doctoral training at the Cold Spring Harbor Laboratory. For his work he has received numerous awards including the Herman Beerman Award, the Wilhelm Bernhard Medal, the Gold Medal of the Charles University, the Flemming Award, the Gian-Tondury Prize, the NIH Director\u2019s Award, and an NIH Merit Award. He acts as an advisor for numerous national and international agencies and serves on several editorial boards including <i>Cell, Science <\/i>and<i> PLoS Biology.\u00a0 <\/i>He is the<i> <\/i>Editor-in-Chief of <i>Current Opinion in Cell Biology.<\/i>\r\n\r\n<hr \/>\r\n\r\n<b><a id=\"Silvia\"><\/a><\/b><strong>August 2016 (start date January 1, 2017): <\/strong>To Silvia Ortega-Guti\u00e9rrez. Associate Professor since 2013, Ram\u00f3n y Cajal Scholar, Organic Chemistry Department 2008-2012, PhD, 2004, Universidad Complutense de Madrid, Spain. She worked under the supervision of Professor Mar\u00eda Luz L\u00f3pez-Rodr\u00edguez, Medicinal Chemistry Department Fulbright Scholar, Professor Ben Cravatt\u2019s Lab, Chemical Biology and Proteomics, The Scripps Research Institute in California, USA; \u201cNew isoprenylcysteine carboxylmethyltransferase (ICMT) inhibitors for the treatment of progeria\"\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Ortega-Gutierrez-Siliva-cr---photo.jpg\" width=\"125\" height=\"133\" \/>In this project we propose the development of new isoprenylcysteine carboxylmethyltransferase (ICMT) inhibitors for the treatment of the Hutchinson-Gilford Progeria Syndrome (HGPS, or progeria) based on a hit previously identified in our research laboratory. This hit (UCM-13239) inhibits ICMT in a significant manner, induces mislocalization of progerin protein in progeroid fibroblasts (LmnaG609G\/G609G), increases viability of these cells and promotes pro-survival signaling pathways in the treated cells. Using this compound as a starting point, our team will carry out a medicinal chemistry program (hit to lead and lead optimization) aimed at obtaining improved compounds in terms of biological activity and pharmacokinetic parameters. The optimal compound(s) will be assessed for efficacy in an in vivo model of progeria.\r\n\r\nSilvia Ortega-Guti\u00e9rrez obtained her PhD degree in Complutense University, in Madrid, working under the supervision of Prof. Mar\u00eda Luz L\u00f3pez-Rodr\u00edguez in the field of Medicinal Chemistry. After that, she joined Prof. Ben Cravatt\u2019s lab at The Scripps Research Institute (California, USA) to work in the field of Chemical Biology and Proteomics with a Fulbright Fellowship. Between 2008 and 2012 she was Ram\u00f3n y Cajal Scholar in the Organic Chemistry Department at Complutense University where she was promoted to Associate Professor in 2013. This is the position that she currently holds.\r\n\r\nDr. Ortega-Guti\u00e9rrez\u2019 areas of interest are medicinal chemistry and chemical biology and, in particular, the fields of the endogenous cannabinoid and lysophosphatidic acid systems, the validation of new therapeutic targets, and the development of chemical probes for the study of G protein-coupled receptors. Her work has been published in prestigious journals including Science, Nature Neuroscience, Angewandte Chemie and the Journal of Medicinal Chemistry, and also in patents that have been transferred to the pharmaceutical industry. In 2011 and in 2016 she received the \u201cRunner-up Prize for a Young Medicinal Chemist in Academia\u201d by the European Federation of Medicinal Chemistry and in 2012 the \u201cYoung Researcher Award\u201d by the Spanish Royal Chemical Society.\r\n\r\n<hr \/>\r\n\r\n<strong>July 2016 (start date October 1, 2016): <\/strong>To Roland Foisner, PhD, Professor of Biochemistry, Medical University Vienna and Deputy Director, Max F. Perutz Laboratories, Vienna, Austria. Scientific coordinator, former European network project EURO-Laminopathies and Editor-in-Chief, journal Nucleus; \u201cContribution of endothelial cell dysfunction to cardiovascular disease in progeria and implications for diagnostic and therapeutic targets.\u201d\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Portrait_Foisner.jpg\" width=\"125\" height=\"152\" \/>Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disease, caused by mutation in the <i>LMNA<\/i> gene and characterized by severe symptoms resembling features of premature aging, including cardiovascular disease that leads to atherosclerosis, hypertension, heart hypertrophy and death due to heart failure. Previous studies in patients and HGPS mouse models revealed progressive loss of smooth muscle cells in blood vessels, but the role of endothelial cells in the development of HGPS-linked cardiovascular disease has not been analyzed yet, despite the fact that impaired endothelial cell function is a major risk factor for cardiovascular disease in normal aging. In order to study the molecular basis of the cardiovascular aging pathology and to investigate how the aged vascular endothelium contributes to HGPS, we generated a novel mouse model expressing the HGPS-causing <i>LMNA <\/i>mutant gene product selectively in the vascular endothelial cell system. Our preliminary analyses of the mice showed retarded growth, increased fibrosis in the heart, cardiac hypertrophy, elevation of hypertrophy markers, and premature death of mutant mice, resembling the HGPS cardiovascular phenotype. In this project we will investigate the molecular mechanisms, how the mutant <i>LMNA <\/i>gene product affects endothelial cells in blood vessel and how this can affect heart function. We will identify pro-atherogenic components secreted in mutant endothelial cells and vessels and test how this pathway can affect other tissues and cells. This project will also identify potential biomarkers for HGPS-linked cardiovascular disease in blood. Our project for the first time investigates the role of the vascular endothelium in the development of cardiovascular disease in HGPS and will identify new (pro-atherogenic) pathways and components as potential targets for diagnosis and therapy.\r\n\r\nRoland Foisner is University Professor of Biochemistry at the Medical University Vienna and Deputy Director at the Max F. Perutz Laboratories. He received his PhD (Dr. techn.) in Biotechnology at the Technical University Vienna, Austria, in 1984, was Assistant and then Associate Professor at the University of Vienna, and was appointed Full Professor at the Department of Medical Biochemistry of the Medical University Vienna in 2002. 1991\u20101992 he received post\u2010doctoral training at the Scripps Research Institute in La Jolla, California, USA.\r\n\r\nRoland Foisner was the scientific coordinator of EURO\u2010Laminopathies, a European network project of clinical and basic researchers, aiming at the analyses of molecular mechanisms of lamin\u2010linked diseases for the development of new therapeutic approaches. He is Editor\u2010in\u2010 Chief of the Journal Nucleus, serves on the Editorial Board of several Cell Biology Journals, in the scientific advisory board of EU projects, and in review panels of several international funding organizations. He was Dean of graduate studies in the International Vienna Biocenter PhD program until 2007 and has served in many national and international thesis committees.\r\n\r\nResearch in Roland Foisner\u2019s lab focuses on the dynamics and functions of lamins and lamin binding proteins in nuclear and chromatin organization, in the regulation of gene expression and signaling, and in genetic diseases ranging from muscular dystrophies to premature aging. He has published numerous important peer\u2010reviewed papers, invited reviews and book chapters, and has given numerous invited seminars at national and international meetings.\r\n\r\n<hr \/>\r\n\r\n<strong>December 2015 (start date January 1, 2016): <\/strong>To Juan Carlos Belmonte Izpisua, PhD, Professor, Gene Expression Laboratories at The Salk Institute for Biological Studies, La Jolla, CA, USA; \u00a0\u00a0\u201cThe use of novel technologies to identify and validate potential therapeutic compounds for the treatment of Hutchinson-Gilford Progeria Syndrome\u201d\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Belmonte%2C-Juan-Carlos.jpg\" width=\"125\" height=\"148\" \/>Cardiovascular alterations are the leading cause of death among Progeria patients. Dr. Belmonte\u2019s laboratory has developed novel models for the study of Progeria based on the use of induced pluripotent stem cells (iPSCs) generated from Progeria patients. His laboratory is now using vascular cells produced from these models for the discovery of novel drugs that can ameliorate cardiovascular alterations in human and mouse models of Progeria. These discoveries could lead to the development of novel treatments for Progeria patients.\r\n\r\nDr. Juan Carlos Belmonte Izpisua is a Professor at the Gene Expression Laboratories at The <a title=\"Salk Institute for Biological Studies\" href=\"https:\/\/en.wikipedia.org\/wiki\/Salk_Institute_for_Biological_Studies\">Salk Institute for Biological Studies<\/a>, La Jolla, CA, USA.\u00a0 He is the former director and assisted in establishing the <a title=\"es:Centro de Medicina Regenerativa de Barcelona\" href=\"https:\/\/es.wikipedia.org\/wiki\/Centro_de_Medicina_Regenerativa_de_Barcelona\">Center for Regenerative Medicine in Barcelona<\/a>. He has a Ph.D. in Biochemistry and Pharmacology from The University of Bologna, Italy and from the University of Valencia, Spain. He is a postdoctoral fellow from the University of Marburg\u2019 European Molecular Biology Laboratory (EMBL), in Heidelberg, Germany and UCLA, USA.\r\n\r\n<hr \/>\r\n\r\n<b><a id=\"Fahey\"><\/a>December 2015 (start date March 1, 2016): <\/b><b>\u00a0<\/b>To Jed William Fahey, Sc.D., Director, Cullman Chemoprotection Center, <i>Assistant Professor, <\/i>Johns Hopkins University, School of Medicine, Department of Medicine, Division of Clinical Pharmacology, Department of Pharmacology & Molecular Sciences; Bloomberg School of Public Health, Department of International Health, Center for Human Nutrition; \u201cThe capacity of plant-derived isothiocyanates to surpass the efficacy of sulforaphane, with reduced toxicity to Progeria cell lines.\u201d\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Fahey%2C-Jed-W.jpg\" width=\"172\" height=\"125\" \/>A recent study by others [Gabriel et al., 2015, <i>Aging Cell<\/i> 14(1):78-91] showed that the isothiocyanate sulforaphane (a phytochemical from broccoli), enhanced the growth rate of cultured cells derived from children with Progeria, and it increased a variety of biomarkers associated with the syndrome.\u00a0 Our work with isothiocyanates from edible plants suggests that some of these hundred-plus closely related compounds should have wider therapeutic windows (the range between effective, and toxic concentration), and perhaps lower effective concentrations than sulforaphane.\u00a0 We will test this hypothesis.\r\n\r\n<hr \/>\r\n\r\n<b>June 2015 (start date July 1, 2015): <\/b>To Bum-Joon Park, PhD, Chairperson and Professor of the Department of Molecular Biology, Pusan National University, Republic of Korea; \u201cImprovement of therapeutic effect of JH4, progerin-lamin A\/C binding inhibitor, against progeria syndrome.<b>\u201d<\/b><b><a id=\"Bum-Joon\"><\/a><\/b>\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Park%2CBum-Joon(2).jpg\" width=\"125\" height=\"163\" \/>We recently found novel chemicals that block the interaction between progerin and Lamin A\/C through chemical library screening. In progerin-producing mouse model (<i>Lmna<sup>G609G\/G609G<\/sup><\/i>), our chemical (JH4) can extend life span as well as ameliorate aging phenotypes including gain of body weight, increase muscle strength and organ size. Despite obvious effect of JH4 on <i>Lmna<sup>wt\/G609G<\/sup><\/i>mice, it can extend only 4 weeks of <i>Lmna<sup>G609G\/G609G<\/sup><\/i> mice life span, indicating that JH4 effect is not enough for applying as therapeutic drug for progeria syndrome at present stage. In addition, improvement of JH4 effect should be performed. For this, we will carry several trials for improvement of JH4 effect. First, we will modify our chemicals more hydrophilic form. In fact, JH4 is very hydrophobic that would be one of reason we cannot increase dosage. Concerning this, we already obtained hydrophilic compound (JH010), with similar cellular effect of JH4. Indeed, our recent result showed that increase of JH4 (from 10 mg\/kg to 20 mg\/kg) could increase life span from 16 week (carrier-treated) over to 24 weeks (actually, 20 mg\/kg-injected mice were still alive). To improve this chemical, we generated JH010-derivetives and checked the biological effect. Second, we will make nanoparticle that will deliver JH010 more effectively to whole body. In fact, this work has been already started. Through both methods, we will obtain improved JH4-related chemicals and will test them in <i>Lmna<sup>G609G\/G609G<\/sup><\/i> mouse model (life span, histological analysis, toxicity, Pharmacodynamics as well as Pharmaco-Kinetics). From these studies, we wish to provide the best way to treatment of HGPS in mouse model as well as HGPS children.\r\n\r\nDr. Park received his PhD in Cancer Biology at Korea University. He carried out his post-doctoral research in the Korea National Institute of Health (KNIH) and in Seoul National University. Since 2006, he has worked at Pusan National University. Now he is the Chairperson of the Department of Molecular Biology. His research focuses on identification of the disease specific signaling network (Cancer, HGPS, Werner syndrome) and finding novel chemicals that can block the disease related protein-protein interaction for drug candidates.\r\n\r\n<hr \/>\r\n\r\n<b>June 2015 (start date September 1, 2015): <\/b>To John P. Cooke, MD, PhD, Joseph C. \u201cRusty\u201d Walter and Carole Walter Looke Presidential Distinguished Chair in Cardiovascular Disease Research, Chair and Full Member of the Department of Cardiovascular Sciences Houston Methodist Research Institute, Director of the Center for Cardiovascular Regeneration Houston Methodist DeBakey Heart and Vascular Center, Houston, TX; \u201cTelomerase Therapy for Progeria.\u201d\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Cooke%2CJohn-P.jpg\" width=\"125\" height=\"187\" \/>In children with progeria, the blood vessels age very quickly. This causes vascular disease that leads to heart attack and stroke. We intend to develop a therapy that reverses vascular aging in these children. We have previously shown that aged human cells can be rejuvenated by treating them with modified message RNA (mmRNA) encoding telomerase.\u00a0 Telomerase is a protein that extends telomeres on chromosomes.\r\n\r\nThe telomeres are like the tip of a shoelace; they hold the chromosome together, and telomeres are necessary for normal functioning of the chromosomes. As cells age, the telomeres get shorter, and at some point the chromosome no longer functions properly.\u00a0 At this point the cell becomes senescent and can no longer proliferate. Telomeres are essentially our biological clock. In children with progeria, the telomeres shorten more quickly. We intend to test our therapy on cells from Progeria children to see if we can extend the telomeres, reverse the aging process, and rejuvenate the vascular cells. If this approach works, we intend to develop the therapy toward clinical trials in these children.\r\n\r\nDr. John P. Cooke trained in cardiovascular medicine and obtained a PhD in physiology at the Mayo Clinic. He was recruited to Harvard Medical School as an assistant professor of medicine. In 1990, he was recruited to Stanford University to spearhead the program in vascular biology and medicine, and was appointed Professor in the Division of Cardiovascular Medicine at Stanford University School of Medicine, and Associate Director of the Stanford Cardiovascular Institute until his recruitment to Houston Methodist in 2013.\r\n\r\nDr. Cooke has published over 500 research papers, position papers, reviews, book chapters and patents in the arena of vascular medicine and biology with over 20,000 citations; h index = 76 (ISI Web of Knowledge, 6-2-13). He serves on national and international committees that deal with cardiovascular diseases, including the American Heart Association, American College of Cardiology, Society for Vascular Medicine, and the National Heart, Lung and Blood Institute. He has served as President of the Society for Vascular Medicine, as a Director of the American Board of Vascular Medicine, and as an Associate Editor of Vascular Medicine.\r\n\r\nDr. Cooke\u2019s translational research program is focused on vascular regeneration. The program is funded by grants from the National Institutes of Health, the American Heart Association, and the industry.\r\n\r\nThe focus of Dr. Cooke\u2019s research program is on restoration or stimulation of endothelial functions such as vasodilation and angiogenesis, using small molecules or stem cell therapies. In his 25 years of translational endothelial biology, he first described and characterized the anti-atherogenic effects of endothelium-derived nitric oxide; the anti-angiogenic effect of the NO synthase inhibitor ADMA; the angiogenic pathway mediated by endothelial nicotinic acetylcholine receptors; the role for this pathway in states of pathological angiogenesis; and developed an antagonist of the pathway that is now in Phase II clinical trials. His clinical research group has explored the use of angiogenic agents and adult stem cells in the treatment of peripheral arterial disease. More recently, he has generated and characterized endothelial cells derived from human iPSCs, and explored their role in angiogenesis and vascular regeneration. Recent insights from the laboratory have clarified the role of innate immune signaling in nuclear reprogramming to pluripotency and therapeutic transdifferentiation for vascular disease.\r\n\r\n<hr \/>\r\n\r\n<b>June 2015 (start date Sep 1, 2015): <\/b>To Francis S. Collins, MD, PhD, Director of the National Institutes of Health (NIH\/NHGRI), Bethesda, MD; \u201cPost-doctoral Candidate Funding for HGPS Research.\u201d\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Collins%2C-Francis(1).jpg\" width=\"125\" height=\"158\" \/>Dr. Collins oversees the work of the world\u2019s largest supporter of biomedical research, from basic to clinical research. Dr. Collins and his team, together with The Progeria Research Foundation,\u00a0co-discovered the genetic cause of HGPS in 2003, and with over a dozen years invested in this work, their aim remains: to understand pathogenesis and seek treatments for HGPS. Current studies are focused on potential therapeutic approaches, including RNA-based methods and the use of rapamycin and its analogs, using both cellular and HGPS mouse models.<b><\/b>\r\n\r\nFrancis S. Collins, M.D., Ph.D. is the Director of the National Institutes of Health (NIH).\u00a0 In that role he oversees the work of the largest supporter of biomedical research in the world, spanning the spectrum from basic to clinical research.\r\n\r\nDr. Collins is a physician-geneticist noted for his landmark discoveries of disease genes and his leadership of the international Human Genome Project, which culminated in April 2003 with the completion of a finished sequence of the human DNA instruction book. He served as director of the National Human Genome Research Institute at the NIH from 1993-2008.\r\n\r\nDr. Collins\u2019 own research laboratory has discovered a number of important genes, including those responsible for cystic fibrosis, neurofibromatosis, Huntington's disease, a familial endocrine cancer syndrome, and most recently, genes for type 2 diabetes, and the gene that causes Hutchinson-Gilford progeria syndrome, a rare condition that causes premature aging.\r\n\r\nDr. Collins received a B.S. in chemistry from the University of Virginia, a Ph.D. in physical chemistry from Yale University, and an M.D. with honors from the University of North Carolina at Chapel Hill. Prior to coming to the NIH in 1993, he spent nine years on the faculty of the University of Michigan, where he was a Howard Hughes Medical Institute investigator. He is an elected member of the Institute of Medicine and the National Academy of Sciences. Dr. Collins was awarded the Presidential Medal of Freedom in November 2007 and the National Medal of Science in 2009.\r\n\r\n<hr \/>\r\n\r\n<b>June 2015 (September 1, 2015): <\/b>To Dudley Lamming, PhD, Assistant Professor in the Department of Medicine at the University of Wisconsin-Madison, Co-Director of the UW Department of Medicine Mouse Metabolic Phenotyping Platform, Madison, WI.\u00a0 \u201cIntervention in Progeria by Restriction of Specific Dietary Amino Acids\u201d\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/LammingDudley.jpg\" width=\"125\" height=\"141\" \/>Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare, fatal genetic disorder characterized by rapid aging. Treatment of human HGPS fibroblasts or mice lacking Lmna (a mouse model of HGPS) with rapamycin, an inhibitor of the mTOR (mechanistic Target Of Rapamycin) protein kinase, reverses HGPS phenotypes at the cellular level, and promotes lifespan and health at the organismal level. However, rapamycin has serious side effects in humans, including immunosuppression and diabetogenic metabolic effects, which may preclude its long-term use for HGPS patients. The mTOR protein kinase is found in two distinct complexes, and the work of Dr. Lamming\u2019s research team and work of many other laboratories suggest that many of the benefits of rapamycin benefits are derived from suppression of mTOR complex 1 (mTORC1), while many of the side effects are due to \u201coff-target\u201d inhibition of mTOR complex 2 (mTORC2).\r\n\r\nWhile rapamycin inhibits both mTOR complexes in vivo, mTORC1 and mTORC2 are naturally responsive to different environmental and nutrient cues. mTORC1 is directly stimulated by amino acids, while mTORC2 is predominately regulated by insulin and growth-factor signaling. Dr. Lamming\u2019s research team have determined that a low protein diet significantly reduces mTORC1, but not mTORC2, signaling in mouse tissues. This raises the intriguing possibility that a low-protein diet may be a relatively simple, low side-effect method to restrain mTORC1 activity and provide therapeutic benefit to HGPS patients.\u00a0 In this study, they will identify a diet that inhibits mTORC1 signaling in vivo, and determine the ability of this diet to rescue HGPS pathology both in vivo in a progerin-expressing mouse model of HGPS, and in vitro in human HGPS patient cell lines.\r\n\r\nDudley Lamming received his PhD in Experimental Pathology from Harvard University in 2008 in the laboratory of Dr. David Sinclair, and subsequently completed postdoctoral training at the Whitehead Institute for Biomedical Research in Cambridge, MA in the laboratory of Dr. David Sabatini. Dr. Lamming\u2019s research is supported in part by a NIH\/NIA K99\/R00 Pathway to Independence Award as well as a Junior Faculty Research Award from the American Federation for Aging Research. His laboratory at the University of Wisconsin is focused on learning how nutrient-responsive signaling pathways can be harnessed to promote health and delay both normal aging as well as diseases of premature aging such as Hutchinson-Gilford Progeria Syndrome.\r\n\r\n<hr \/>\r\n\r\n<b>June 2015 (start date September 1, 2015): <\/b>To Cl\u00e1udia Cavadas, PhD, Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra Portugal; \u201cPeripheral NPY reverts HGPS phenotype: a study in human fibroblasts and mouse model.\u201d\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Cavadas%2C-Claudia-(1).jpg\" width=\"125\" height=\"137\" \/>Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare genetic disease characterized by premature and accelerated aging, and premature death. The discovery of new therapeutic compounds is of utmost importance for this fatal disease. The endogenous molecule neuropeptide Y (NPY) activates NPY receptors that are localized in various organs and cells affected by HGPS. Our preliminary data and recent publications strongly suggest that neuropeptide Y (NPY) system might be a putative therapeutic target for HGPS.\r\n\r\nIn this study we will investigate the beneficial effects of NPY and\/or activators of NPY receptors in rescuing the aging phenotype in two HGPS models: in cell based and mouse model of HGPS. With this project we expect to show that NPY system activation is an innovative strategy for the therapeutics, or co-therapeutics, of HGPS.\r\n\r\nCl\u00e1udia Cavadas holds a PhD in Pharmacology from the Faculty of Pharmacy, University of Coimbra. She is Group Leader of \u201cNeuroendocrinology and Aging group\u201d at CNC - Center for Neuroscience and Cell Biology, University of Coimbra. Cl\u00e1udia Cavadas is co-author of 50 publications and has been investigating the Neuropeptide Y (NPY) system since 1998. She is the vice-president of the Portuguese Society of Pharmacology (since 2013); Cl\u00e1udia Cavadas was the former Director of the Institute for Interdisciplinary Research of the University of Coimbra (2010-2012).\r\n\r\n<hr \/>\r\n\r\n<b>December 2014 (start date April 1, 2015):\u00a0<\/b>To C\u00e9lia Alexandra Ferreira de Oliveira Aveleira, PhD, Center for Neuroscience and Cell Biology (CNC) and Institute for Interdisciplinary Research (IIIUC), University of Coimbra Portugal; \u201cGhrelin: a novel therapeutic intervention to rescue the phenotype of Hutchinson\u2010Gilford Progeria Syndrome\u201d\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Celia-Aveleira-pic.jpg\" width=\"125\" height=\"174\" \/>Hutchinson-Gilford progeria syndrome (HGPS), a lethal genetic disorder, is characterized by premature accelerated aging. HGPS is most commonly caused by a de novo point mutation (G608G) within the lamin A\/C gene (LMNA), producing an abnormal lamin A protein termed progerin. Accumulation of progerin causes nuclear abnormalities, and cell cycle arrest, ultimately leading to cellular senescence, and therefore, is one of the mechanisms underlying the progression of HGPS. It has been shown that rapamycin, by stimulating autophagy, promotes clearance of progerin and has beneficial effects on HGPS models. Since rapamycin has well-known adverse effects, the identification of safer stimulators of autophagy, with other beneficial effects, for chronic treatment of HGPS patients is of utmost importance.\r\n\r\nGhrelin is a circulating peptide hormone, and is the endogenous ligand for growth hormone secretagogue receptor, having, therefore, growth hormone-releasing activity. Apart from its well-known orexigenic effect, ghrelin has beneficial roles in different organs and systems, such as cardiovascular protective effect, atherosclerosis regulation, protection from ischemia\/reperfusion injury as well as improving the prognosis of myocardial infarction and heart failure. Moreover, ghrelin and ghrelin analogues have been tested in some clinical trials for the treatment of diseases such as cachexia in chronic heart failure, frailty in elderly, and growth hormone deficiency-related disorders, and therefore, can be considered as a safe therapeutic strategy. Additionally, our very recent data show that ghrelin stimulates autophagy and promotes progerin clearance in HGPS cells. In this study we will investigate the potential of ghrelin and ghrelin receptor agonist as treatment for HGPS. Toward this end, we will evaluate whether peripheral administration of ghrelin\/ghrelin receptor agonist can ameliorate HGPS phenotype and increase lifespan, using the LmnaG609G\/G609G mice, a HGPS mouse model. In addition, we will also determine whether ghrelin reverses HGPS senescent cellular phenotype by promoting progerin clearance through autophagy, a mechanism by which cells clear unnecessary or dysfunctional proteins and organelles to maintain cell homeostasis.\r\n\r\nC\u00e9lia Aveleira received her PhD in Biomedical Sciences from University of Coimbra, Portugal, in 2010. She performed her thesis studies at the Centre of Ophthalmology and Vision Sciences, Faculty of Medicine, University of Coimbra, Portugal and Department of Cellular and Molecular Physiology, Penn State College of Medicine, Penn State University, Hershey, Pennsylvania, USA. After that, she joined Cl\u00e1udia Cavadas\u2019s research group at the Centre for Neuroscience and Cell Biology, University of Coimbra, Portugal, to conduct her postdoctoral studies. She was granted with a FCT Post-Doc fellowship to study the potential role of neuropeptide Y (NPY) as a mimetic of caloric restriction to reduce aging and ameliorate age-related diseases. In 2013 she assumed her current position at CNC, as an Invited Scientist Research fellow. Her research centers on the role of caloric restriction mimetics as therapeutics targets to delay the aging process of normal and premature aging diseases, such as Hutchinson-Gilford progeria syndrome (HGPS), with particular focus on the homeostatic mechanisms, such as autophagy and tissue regenerative capacity of stem\/progenitor cells.\r\n\r\n<hr \/>\r\n\r\n<a id=\"JCobos\"><\/a><strong>December 2014 (start date February 1, 2015): <\/strong>To Jes\u00fas V\u00e1zquez Cobos, PhD, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain; \u201cQuantitation of Farnesylated Progerin in Progeroid Mouse Tissues and Circulating Leukocytes from Hutchinson-Gilford Progeria Patients\u201d\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/jvazquezpic.jpg\" width=\"125\" height=\"166\" \/>Hutchinson-Gilford progeria syndrome (HGPS) is a rare disorder characterized by premature severe aging and death (median age of 13.4 years). By far, the most common cause of HGPS is a mutation in the gene coding for the protein lamin A that results in the accumulation of progerin, a modified form of lamin A that contains a chemical modification called farnesylation and that is thought to produce the pathology. Hence, scientists are trying to develop therapies that prevent this modification. However, analyzing the results of these experimental therapies is challenging because to date no reliable methods exist to measure the levels of farnesylated progerin in animal models or in HGPS patients. The researchers from CNIC have demonstrated that the levels of the modified protein can be reliably quantified in cultured fibroblasts (a preparation of cells that are obtained from the skin) from mouse and also from HGPS by using a technique called mass spectrometry. In the current project, these researchers are trying to improve the technique to be able to quantify farnesylated progerin directly in blood samples from HGPS patients. If successful the technique would provide scientists with an invaluable tool to evaluate the efficacy of experimental treatments in humans and to monitor the progression and severity of this disease.\r\n\r\nDr. Jes\u00fas V\u00e1zquez graduated in Physical Chemistry at the Universidad Complutense (Madrid, 1982) and carried out his PhD in Biochemistry at the Universidad Aut\u00f3noma (Madrid, 1986), both with Special Distinction. During his postdoctoral training at Merck Sharp Research Laboratories (NJ, USA) and at the Centro de Biolog\u00eda Molecular Severo Ochoa (Madrid), he specialized in protein chemistry and in the study of biomembranes in the context of neurochemical diseases. Since then, he has played a pioneering role in the development of protein chemistry, mass spectrometry and proteomics in Spain. His laboratory has made relevant contributions to the field addressing subjects such as peptide fragmentation mechanisms, de novo peptide sequencing, and analysis of posttranslational modifications. In the last years he has devoted a considerable effort in the development of second generation techniques, relative proteome quantification by stable isotope labeling, advanced algorithms for quantitative data integration and systems biology, and high-throughput characterization of modifications produced by oxidative stress. These techniques have been applied to several research projects, where he is studying the molecular mechanisms underlying processes such as angiogenesis and nitroxidative stress in endothelium, ischemia-preconditioning in cardiomyocites and mitochondria and the interactome at the immune synapse and in exosomes. Author of more than one hundred international publications, he is Profesor de Investigaci\u00f3n of the CSIC and director of the Proteomics Platform of the RIC (Spanish Cardiovascular Research Network). He joined the CNIC as a Full Professor in 2011, where he leads the Cardiovascular Proteomics laboratory and is also in charge of the Proteomics Unit.\r\n\r\n<hr \/>\r\n\r\n<b>December 2014 (<strong>start date February 1, 2015<\/strong>): <\/b>To Marsha Moses, PhD, Boston Children\u2019s Hospital, Boston, MA; \u201cDiscovering Novel Non-Invasive Biomarkers for Hutchinson-Gilford Progeria Syndrome\u201d\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Moses.jpg\" width=\"125\" height=\"186\" \/>Our goal is to improve our collective understanding of disease development and progression through biomarker identification, with the goal of advancing current treatment and developing and assessing novel therapies for Hutchinson-Gilford Progeria Syndrome (HGPS), and potentially for cardiovascular disease (CVD) in the general population. To date, there is <i>no <\/i>consistent ability to determine who is at risk of progression or who will respond to therapy. Accurate tests, based on a specific, definable marker or panel of markers are essential in order to standardize clinical guidelines, diagnosis and management. We intend to utilize a state of the art proteomics discovery approach to meet our goal of discovering and validating minimally invasive biomarkers of HGPS and potentially of aging and cardiovascular disease. The insight gained in these studies of HGPS will inform and significantly expand our knowledge of the mechanisms underlying HGPS.\u00a0 The strong potential also exists that the biomarker discoveries made in these studies may ultimately represent potential therapeutic targets for HGPS, CVD and other aging-related disorders.\r\n\r\nDr. Marsha A. Moses is the Julia Dyckman Andrus Professor at Harvard Medical School and the Director of the Vascular Biology Program at Boston Children's Hospital.\u00a0She has had a long-standing interest in identifying and characterizing the biochemical and molecular mechanisms that underlie the regulation of tumor growth and progression.\u00a0Dr. Moses and her laboratory have discovered a number of angiogenesis inhibitors that function at both the transcriptional and translational level, some of which are in preclinical testing. Named a pioneer in the exciting field of Biomarker Medicine by the <i>Journal of the National Cancer Institute<\/i>, Dr. Moses established a Proteomics Initiative in her laboratory that has led to the discovery of panels of noninvasive urinary cancer biomarkers that can predict disease status and stage in cancer patients and that are sensitive and accurate markers of disease progression and therapeutic efficacy of cancer drugs. A number of these urine tests have been made commercially available. These diagnostics and therapeutics are included in Dr. Moses\u2019 significant patent portfolio which is composed of both US and foreign patents.\r\n\r\nDr. Moses\u2019 basic and translational work has been published in such journals as <i>Science<\/i>, the <i>New England Journal of Medicine<\/i>, <i>Cell<\/i> and the <i>Journal of Biological Chemistry<\/i>, among others.\u00a0Dr. Moses received a Ph.D. in Biochemistry from Boston University and completed a National Institutes of Health postdoctoral fellowship at Boston Children's Hospital and MIT. She is the recipient of a number of NIH and foundation grants and awards. Dr. Moses has been recognized with both of Harvard Medical School's mentoring awards, the A. Clifford Barger Mentoring Award (2003) and the Joseph B. Martin Dean\u2019s Leadership Award for the Advancement of Women Faculty (2009). In 2013, she received the Honorary Member Award from the Association of Women Surgeons of the American College of Surgeons.\u00a0 Dr. Moses was elected to the <i>Institute of Medicine<\/i> of the <i>National Academies of the United States<\/i> in 2008 and to the <i>National Academy of Inventors<\/i> in 2013.<b><\/b>\r\n\r\n<hr \/>\r\n\r\n<strong>December 2014 (start date March 1, 2015): <\/strong>To Joseph Rabinowitz, PhD, Temple University School of Medicine, Philadelphia, PA; \u201cAdeno-associated virus mediated co-delivery of wild type lamin A and microRNA against progerin\u201d\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/JRabinowitz-pic.jpg\" width=\"125\" height=\"187\" \/>Adeno-associated virus (AAV) is a small, non-disease causing DNA virus that is being used to delivery non-viral genes and other therapeutic DNAs to animals and man. The entire viral genome, except 145 bases on each end, can be removed so that no viral genes are included in the DNA that is packaged within the virus shell (virion). MicroRNAs (miRs) are small pieces of RNA that reduce protein expression by interfering with the corresponding messenger RNA of that protein(s). Research has demonstrated that Lamin A (LMNA) is not expressed at high levels in the brain, and miR-9 expression in the brain is responsible for that suppression. We will package miR-9 in an AAV genome and examine the level of LMNA suppression in human progeria and age matched non-progeria cell lines. In addition, we will package miR-9 and LMNA (that cannot be suppressed by miR-9) in AAV and examine cells for rescue of progeria phenotype. If these steps are successful we will repeat them in a mouse model of Progeria.\r\n\r\nJoseph Rabinowitz, PhD, is Assistant Professor of Pharmacology Center for Translational\u00a0Medicine Temple University School of Medicine in Philadelphia Pennsylvania. Dr. Rabinowitz\u00a0received his PhD in Genetics at Case Western Reserve University in Cleveland Ohio\u00a0(Professor Terry Magnuson, PhD). He carried out his postdoctoral studies at the University\u00a0of North Carolina at Chapel Hill in the Gene Therapy Center (R. Jude Samulski, Director)\u00a0were he begun working with Adeno-associated virus as a gene therapy vehicle. In 2004,\u00a0joined the faculty of Thomas Jefferson University the focus of his lab has been development\u00a0of Adeno-associated virus serotypes as gene delivery vehicles to the heart. In 2012 he\u00a0moved to Temple University School of Medicine and is Director of the viral vector core.\u00a0Viruses can be used as tools to delivery therapeutic genes to experimental animals and in\u00a0clinical trials to humans.\r\n\r\n<hr \/>\r\n\r\n<strong>July 2014 (start date November 1, 2014): <\/strong>To Vicente Andr\u00e9s Garc\u00eda, PhD, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain; \u201c\u201cGeneration of a HGPS Knock-in Pig Model to Expedite the Developement of Effective Clinical Applications\u201d.\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/V_Andres.jpg\" width=\"125\" height=\"158\" \/>Principal Investigator: Vicente Andr\u00e9s, PhD, Laboratory of Molecular and Genetic Cardiovascular Pathophysiology, Department of Epidemiology, Atherothrombosis and Imaging, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.\r\n\r\nHutchinson-Gilford progeria syndrome (HGPS) is caused by mutations in the <i>LMNA<\/i> gene that lead to the production of progerin, an abnormal protein that retains a toxic farnesyl modification. HGPS patients exhibit widespread atherosclerosis and die predominantly from myocardial infarction or stroke at an average age of 13.4 years, yet very little is known about the mechanisms through which progerin accelerates cardiovascular disease (CVD). More preclinical research is therefore needed to find a cure for HGPS.\r\n\r\nUnlike trials for prevalent diseases, clinical trials for HGPS patients will always be limited by small cohort size. It is therefore of the utmost importance to perform preclinical studies in the most appropriate animal models. Nowadays, genetically-modified mouse models are the gold-standard for preclinical studies of HGPS. However, mice do not faithfully recapitulate all aspects of human pathology. Compared with rodents, pigs more closely resemble humans in body and organ size, anatomy, longevity, genetics and pathophysiology. Remarkably, atherosclerosis in pigs closely recapitulates the main morphological and biochemical characteristics of the human disease, including the shape and distribution of atherosclerotic plaques, which predominantly accumulate in aorta, coronary arteries and carotid arteries. Our main objective is to generate and characterize genetically-modified pigs carrying the<i> <\/i><i>LMNA<\/i> c.1824C>T mutation, the most frequent mutation in HGPS patients. Research using this large animal model should permit major advances in our basic knowledge of CVD in progeria and expedite the development of effective clinical applications.\r\n\r\nVicente Andr\u00e9s obtained his PhD in Biological Sciences from the University of Barcelona (1990). During postdoctoral training at the Children's Hospital, Harvard University (1991-1994) and the St. Elizabeth's Medical Center, Tufts University (1994-1995), he led studies into the role of homeobox and MEF2 transcription factors in processes of cellular differentiation and proliferation; and it was also during this period that he developed an interest in cardiovascular research. His career as an independent research scientist began in 1995 when he was appointed Assistant Professor of Medicine at Tufts. Since then Dr. Andr\u00e9s and his group have studied vascular remodeling during atherosclerosis and post-angioplasty restenosis, and more recently they investigate the role of the nuclear envelope in the regulation of signal transduction, gene expression and cell-cycle activity in cardiovascular disease and aging, with particular emphasis on A-type lamins and Hutchinson-Gilford progeria syndrome (HGPS).\r\n\r\nAfter obtaining a position as a Tenured Research Scientist in the Spanish National Research Council (CSIC), Dr. Andr\u00e9s returned to Spain in 1999 to establish his research group in the Institute of Biomedicine of Valencia, where he worked as a Full Professor. Since 2006, his group has been a member of the Red Tem\u00e1tica de Investigaci\u00f3n Cooperativa en Enfermedades Cardiovasculares (RECAVA). He joined the Centro Nacional de Investigaciones Cardiovasculares (CNIC) in September 2009. In 2010 he was awarded the Doctor Leon Dumont Prize by the Belgian Society of Cardiology.\r\n\r\n<hr \/>\r\n\r\n<strong>June 2013 (start date September 1, 2013): <\/strong>To Dr. Brian Snyder, PhD, : Beth Israel Deaconess Medical Center, Boston, MA.; \u201cCharacterization of the Musculoskeletal, Craniofacial and Skin Phenotypes of the G608G Progeria Mouse Model\u201d.\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/snyder_1.jpg\" width=\"144\" height=\"129\" \/>\r\n\r\nA mouse model of Progeria has been developed at the NIH that has the same musculoskeletal characteristics observed in children with Progeria. To date, there has not been an in depth evaluation of musculoskeletal progeria features in this animal model. Specially, the issue of joint stiffness has also not been evaluated in detail, and It is unclear whether this is a consequence of changes in the skin, muscle, joint capsule, articular cartilage or joint deformity.\r\n\r\nWe will conduct a thorough evaluation of this mouse model using total body CAT scans of the skeleton and vasculture and the joints. We\u2019ll also conduct biomechanical studies of bone, cartilage and skin to characterize changes (compared to normal animal) in shape of the bone, calcification of the blood vessels, changes in the skull and the skin.\r\n\r\nWe will also assess the extent that these phenotypic changes are inter-related and whether these changes can be used to track disease severity and the response to treatment. For example are changes in the musculoskeletal system predictive of changes in the vasculature?\r\n\r\nBrian D. Snyder, M.D., Ph.D. is a Board Certified Pediatric Orthopaedic surgeon on staff at Boston Children\u2019s Hospital, where his clinical practice focuses on hip dysplasia and acquired deformities about the hip, spinal deformity, cerebral palsy and pediatric trauma. He is director of the Cerebral Palsy clinic at Boston Children\u2019s Hospital. In addition, he is an Associate Professor of Orthopaedic Surgery, Harvard Medical School and Associate Director of The Center for Advanced Orthopaedic Studies (CAOS) at Beth Israel Deaconess Medical Center (formerly the Orthopaedic Biomechanics Laboratory). The Laboratory is a multi-disciplinary core research facility associated with the Departments of Bioengineering at Harvard University, Massachusetts Institute of Technology, Boston University, Harvard Medical School and the Harvard Combined Orthopaedic Residency Program. Dr. Snyder has merged the sophisticated analytic techniques developed in the Laboratory with the innovative diagnostic and surgical techniques developed at Children\u2019s Hospital for treating musculoskeletal diseases. Dr. Snyder\u2019s group focuses on basic and applied research in musculoskeletal biomechanics including: characterization of bone structure-property relationships; prevention of pathologic fractures as a consequence of metabolic bone diseases and metastatic cancer; biomechanical analysis of mechanisms of spine injury and development of technology to evaluate the biochemical and biomechanical properties of hyaline cartilage in synovial joints. Dr. Snyder will analyze the changes in the axial and appendicular skeleton of the homozygous mouse model of the G609G gene mutation in the LMNA gene that leads to Hutchinson-Gilford Progeria syndrome (HGPS) using the CT based structural rigidity analysis software package that his lab has developed and validated to accurately predict fracture risk in children and adults with benign and malignant bone neoplasms and measure the response of the appendicular skeleton to treatment in children affected by Progeria.\r\n\r\n<hr \/>\r\n\r\n<strong>June 2013 (start date September 1, 2013): <\/strong>To Dr. Robert Goldman, PhD, : Northwestern University; \u201cNew Insights into the Role of Progerin in Cellular Pathology\u201d.\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Goldman-RD-portrait-2007-2010.jpg\" width=\"150\" height=\"219\" \/>Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare segmental premature aging disorder in which affected children acquire several phenotypic characteristics of accelerated aging. The majority of HGPS cases are caused by a de novo mutation in the gene encoding lamin A (LA) that activates a cryptic splice site in the primary transcript. The resulting mRNA encodes a permanently farnesylated LA with a 50 amino acid deletion in the carboxyl terminal domain called progerin. Although this permanently farnesylated progerin has been demonstrated to be the causative factor in the disease, the mechanism by which the abnormal protein exerts its effects remain unknown. Recently, Dr. Goldman and others have mapped many of the post-translational modification sites in LA. Recently he has observed that LA contains three distinct regions of phosphorylated serine and threonine residues in its unstructured non-\u03b1-helical C- and N- terminal domains. One of these regions is entirely within the 50 amino acid peptide deleted in progerin, suggesting that this region and its post-translational modification could be involved in LA processing and function. His lab also identified several phosphorylation sites that have a high turnover of phosphorylation during interphase. These include the two major phosphorylation sites previously shown to be important for lamin disassembly and assembly at mitosis. Another high turnover site is present in the region near the carboxyl terminus and is deleted in progerin. Preliminary experiments indicate that these high turnover sites are involved in the regulation of LA localization and mobility. Dr. Goldman will investigate the role of site-specific phosphorylation in the processing, localization, mobility and assembly of LA and progerin into a lamina structure. The proposed studies may shed new light on the function of post-translational modifications of specific sites within LA, especially those which are deleted in progerin. The results should provide new insights into the etiology of HGPS. The findings from these studies may also point to new therapeutic interventions for HGPS patients, targeting modifications to LA that are important for regulating lamin functions.\r\n\r\nRobert D. Goldman, PhD, is the Stephen Walter Ranson Professor and Chairman of the Department of Cell and Molecular Biology at Northwestern University Feinberg School of Medicine. He is an authority on the structure and function of the cytoskeletal and nucleoskeletal intermediate filament systems. He and his colleagues have published over 240 scientific articles. His work has led to a number of honors and awards, including an Ellison Foundation Senior Scholar Award in human aging and a MERIT award from the National Institute of General Medical Sciences. Dr. Goldman is a Fellow of the American Association for the Advancement of Science, and served on its board of directors from 1997-2001. He has held numerous positions in the scientific community, including organizing meetings and editing monographs and lab manuals for the Cold Spring Harbor Laboratory and has served on review committees for the American Cancer Society and the NIH. He was President of the American Society for Cell Biology and of the American Association of Anatomy, Cell Biology and Neuroscience Chairpersons. Goldman founded and for many years directed the Science Writers Hands On Fellowship Program at the Marine Biological Laboratory (MBL) and served on the MBL Board of Trustees, as Director of the MBL\u2019s Physiology Course and was Director of the MBL\u2019s Whitman Research Center. He is an Associate Editor of the FASEB Journal, the Molecular Biology of the Cell and Bioarchitecture. He also serves on the Editorial Boards of Aging Cell and Nucleus.\r\n\r\n<hr \/>\r\n\r\n<strong>June 2013 (start date September 1, 2013): <\/strong>To Dr. Christopher Carroll, PhD, : Yale University, New Haven, CT.; \u201cRegulation of progerin abundance by the inner nuclear membrane protein Man1\u201d.\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Carroll.jpg\" width=\"150\" height=\"176\" \/>The molecular mechanisms that control the abundance of Lamin A protein are not well understood. We have shown that the inner nuclear membrane protein Man1 prevents the accumulation of Lamin A in human cells. We will determine whether Man1 also acts to limit the accumulation of progerin, the mutant form of Lamin A that causes Hutchison-Gilford Progeria Syndrome (HGPS), and if so, whether this pathway represents a novel target for therapeutics that delay or prevent the accumulation of progerin in children with HGPS.\r\n\r\nTopher Carroll was a graduate student in the lab of David Morgan at University of California San Francisco where he studied the enzymology of the anaphase-promoting complex. He then went to Aaron Straight's lab in the Dept. of Biochemistry at Stanford University to explore the epigenetic mechanisms that regulate centromere assembly and propagation. Topher started his own lab in the Dept. of Cell Biology at Yale University in the spring of 2012. His lab is interested in nuclear organization and its relationship to chromatin structure and human disease.\r\n\r\n<hr \/>\r\n\r\n<strong>June 2013 (start date September 1, 2013): <\/strong>To Dr. Katharine Ullman,: University of Utah, Salt Lake City, UT; \"Elucidating how progerin impacts the role of Nup153 in the DNA damage response\u201d.\r\n\r\n<strong><img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Ullman.jpg\" width=\"150\" height=\"176\" \/><\/strong>This project aims to gain new insight into the etiology of Hutchinson-Gilford Progeria Syndrome (HGPS) by tackling how mutation in lamin A \u2013which results in expression of a mutated form of lamin A termed progerin\u2013alters the function of the protein Nup153, especially in the context of DNA damage. Nup153 is a component of a large structure called the nuclear pore complex and is recently recognized to participate in the cellular response to DNA damage. Lamin A is known to interact with Nup153 and also participates in the response to DNA damage. We will study this functional intersection, and build on these connections with the goal of rapidly integrating new information into the context of HGPS.\r\n\r\nKatie Ullman received a BA from Northwestern University and then attended Stanford University for her PhD studies. Following a postdoctoral fellowship at University of California, San Diego, she joined the faculty of the University of Utah in 1998. Katie is a member of the Departments of Oncological Sciences and Biochemistry, as well as an Investigator in the Huntsman Cancer Institute. She is the recipient of a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund and co-leads the Cell Response and Regulation Program in the Cancer Center.\r\n\r\n<hr \/>\r\n\r\n<strong>June 2013 (start date September 1, 2013): <\/strong>To Dr. Katherine Wilson,: Johns Hopkins School of Medicine, Baltimore, MD;\u00a0\u201cNatural expression of progerin and consequences of reduced lamin A tail O-GlcNAcylation\u201d.\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Katherine%20Wilson.jpg\" width=\"150\" height=\"181\" \/>Progerin has been viewed as an \u2018unnatural\u2019 form of lamin A. However new work suggests progerin is expressed at high levels at two specific times and places in the human body\u2014after birth when the newborn heart is being remodeled (closure of the ductus arteriosus), and in cells (fibroblasts) exposed to ultraviolet (UV-A) light. This suggests progerin is a natural gene product that is expressed at specific times, for specific (unknown) reasons. A basic understanding of these proposed \u2018natural\u2019 roles of progerin might identify new pathways that could be targeted therapeutically in HGPS. Starting with newborn cow hearts, and UVA-irradiated fibroblasts, this project will purify and identify proteins that associate with progerin, and evaluate their known or potential impact on HGPS. We will also test the possibility that progerin escapes regulation by an essential enzyme (\u2018OGT\u2019; O-GlcNAc Transferase) that normally \u2018tags\u2019 the lamin A tail with many copies of a small sugar (\u2018GlcNAc\u2019). This project will identify sugar-modified site(s) in lamin A versus progerin, ask if these modifications promote healthy lamin functions, and determine if they are influenced by drugs in HGPS clinical trials.\r\n\r\nKatherine Wilson, PhD, Katherine L. Wilson grew up in the Pacific Northwest. She studied microbiology in Seattle (BS, University of Washington), biochemistry and genetics in San Francisco (PhD, UCSF) and began exploring nuclear structure as a postdoctoral fellow in San Diego (UCSD). She then joined the faculty at Johns Hopkins University School of Medicine in Baltimore, where she is Professor of Cell Biology. Her lab studies the \u2018trio\u2019 of proteins (lamins, LEM-domain proteins and their enigmatic partner, BAF) that form nuclear 'lamina' structure, to understand how mutations in these proteins cause muscular dystrophy, heart disease, lipodystrophy, Hutchinson-Gilford Progeria Syndrome and Nestor-Guillermo Progeria Syndrome.\r\n\r\n<hr \/>\r\n\r\n<strong>June 2013 (start date September 1, 2013): <\/strong>To Dr. Brian Kennedy,: Buck Institute for Research on Aging, Novato, CA;\u00a0\u201cSmall Molecule Aging Intervention in Progeria\u201d.\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/KennedyMug.jpg\" width=\"150\" height=\"157\" \/>\r\n\r\nHe is actively involved in aging research in the Pacific Rim, which features the largest elderly population in the world. He is a visiting professor at the Aging Research Institute at Guangdong Medical College in China. He is also an Affiliate Professor in the Department of Biochemistry at the University of Washington, Seattle.\r\n\r\nMutations in A-type nuclear lamins give rise to a range of diseases termed laminopathies, which are associated with cardiovascular disease, muscular dystrophy and progeria. Among these are a subset, which affect C-terminal processing lamin A, and give rise to progeroid syndromes that resemble accelerated aging. The question as to whether or not progerias are mechanistically related to the events that drive normal aging has plagued the aging field for decades with respect to both Werner\u2019s and Hutchison-Gilford Progeria syndromes. Small molecules have recently been identified that slow aging (rapamycin) and protect against age-associated chronic diseases (rapamycin and resveratrol). If progeria is linked mechanistically to normal aging, these small molecules and others that are emerging may be effective agents in the treatment of HGPS. In this study, Dr. Kennedy\u2019s lab plans to employ mouse models of progeria to evaluate the efficacy of resveratrol and rapamycin (as well as derivatives of both agents) toward ameliorating disease pathology.\r\n\r\nBrian K. Kennedy, PhD is President and Chief Executive Officer of Buck Institute for Research on Aging He is internationally recognized for his research in the basic biology of aging and as a visionary committed to translating research discoveries into new ways of detecting, preventing and treating age-related conditions. These include Alzheimer\u2019s and Parkinson\u2019s diseases, cancer, stroke, diabetes and heart disease among others. He leads a team of 20 principal investigators at the Buck Institute - all of whom are involved in interdisciplinary research aimed at extending the healthy years of life.\r\n\r\n<hr \/>\r\n\r\n<strong>December 2012 (start date August 2013): \u00a0<\/strong>To Dr. Gerardo Ferbeyre, PhD, University of Montreal, Montreal, Canada: \"Control of progerin clearance by defarnesylation and phosphorylation at serine 22\"\r\n\r\nThe accumulation of progerin, an altered form of lamin A, causes the Hutchinson-Gilford Progeria syndrome. The ideal treatment for the disease should prevent the accumulation of progerin by decreasing its synthesis or promoting its degradation. However, little is known about the normal turnover of lamin A or progerin. The accumulation of progerin in nuclear lamina is controlled by farnesylation. We have found that lamin A farnesylation controls its phosphorylation at serine 22, an event previously linked to depolimerazation of the nuclear lamina during mitosis. However, we have found that S22 phosphorylation also occurs during interphase and is associated to the generation of progerin cleavage fragments. We propose a new pathway for progerin turnover that includes defarnesylation and S22 phosphorylation. We think that a molecular understanding of this pathway can leads to novel therapeutic possibilities for progeria. In particular the identification of kinases and phosphatases regulating the phosphorylation of lamin A at serine 22 and proteases mediating lamin A tunover will help to identify drugs that stimulate progerin turnover and improve HGPS patients.\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/G%20Ferbeyre.jpg\" alt=\"\" width=\"150\" height=\"189\" \/>Dr Gerardo Ferbeyre graduated from Medical School at the University of Havana, Cuba in 1987 and has a PhD in biochemistry from the University of Montreal in Canada where he studied ribozymes.\u00a0 He did postdoctoral training at Cold Spring Harbor Laboratory with Dr. Scott Lowe. There he established a link between the promyelocytic leukemia protein PML and oncogene-induced senescence and studied the role of p53 and p19ARF as mediators of cellular senescence. In October 2001, Dr Ferbeyre joined the Department of biochemistry of the University of Montreal to continue his scientific research on senescence and the possibilities to reactivate the promyelocytic leukemia protein to treat cancers. Recent contributions from his laboratory include the discovery that DNA damage signaling mediates senescence and a link between defects in lamin A expression and senescence.\r\n\r\n<hr \/>\r\n\r\n<strong>December 2012 (start date February 2013): <\/strong>To Dr. Thomas Misteli, PhD, National Cancer Institute NIH, Bethesda, MD: \"Small molecule discovery in HGPS\"\r\n\r\nDr. Misteli\u2019s team is developing novel therapeutic strategies for Progeria. His group\u2019s work focuses on interfering with the production of the progerin protein using molecular tools and to find novel small molecules to counteract the detrimental effects of progerin in patient cells. These efforts will lead to a detailed cell biological understanding of Progeria cells and will bring us closer to a molecularly targeted therapy for Progeria.\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/MISTELI_portrait2007small.jpg\" alt=\"\" width=\"150\" height=\"130\" \/>\r\n\r\nTom Misteli is an internationally renowned cell biologist who pioneered the use of imaging approaches to study genomes and gene expression in living cells. He is a Senior Investigator and Associate Director at the National Cancer Institute, NIH. His laboratory\u2019s interest is to uncover fundamental principles of spatial genome organization and to apply this knowledge to the development of novel diagnostic and therapeutic strategies for cancer and aging. He has received numerous awards including the Gold Medal of the Charles University, the Flemming Award, the Gian-Tondury Prize, the NIH Director\u2019s Award, and an NIH Merit Award. He acts as an advisor for numerous national and international agencies and serves on several editorial boards including Cell. He is the Editor-in-Chief of The Journal of Cell Biology and of Current Opinion in Cell Biology.\r\n\r\n<hr \/>\r\n\r\n<strong>December 2012 (start date April or May 2013): <\/strong>To Karima Djabali, PhD, Technical University of Munich, Munich, Germany: \"Progerin dynamics during cell cycle progression\"\r\n\r\nHutchinson-Gilford progeria syndrome (HGPS) is caused by mutations in the lamin A gene, which results in the production and accumulation of a mutant prelamin A protein termed progerin. Because this protein accumulates and interferes with nuclear components and functions, identifying progerin direct effectors during mitosis and differentiation is crucial for understanding how and when progerin triggers the nuclear defects that lead cells to premature senesce.\r\n\r\nIn this study Dr. Djabali lab\u2019s plans to identify progerin direct effectors within the nuclear scaffold, nuclear envelope, and nuclear interior to determine the initial molecular interactions that are disrupted by progerin expression. Toward this end, they will use anti-progerin antibodies and HGPS cellular models, including fibroblasts and skin derived-precursor cells established from skin biopsies derived from patients with HGPS (PRF Cell Bank). They will combine biochemical and cellular imaging to identify progerin effectors and investigate their contribution to the molecular events leading to the typical phenotypic changes observed in HGPS cells that are responsible for the development of HGPS disease. Insights gained from these studies will permit the identification of new therapeutic targets for HGPS treatment and new cellular endpoints for testing the efficacy of potential interventions. We hope that our work will provide the knowledge necessary to bring us and other teams in the HGPS field closer to finding a cure(s) that will help children with HGPS live a longer healthy life.\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/djabali-photo.jpg\" alt=\"\" width=\"150\" height=\"225\" \/>\r\n\r\nKarima Djabali, PhD, is Professor of Epigenetics of Aging, Faculty of Medicine, Department of Dermatology and Institute for Medical Engineering (IMETUM) at the Technical University of Munich Germany. Dr. Djabali received her MSc and PhD in Biochemistry at the University Paris VII. She performed her thesis work at the College de France (Prof. F. Gros lab, France) and at the Rockefeller University (Prof. G. Blobel lab, USA). She carried out her postdoctoral research at EMBL (Heidelberg, Germany). She received a Charg\u00e9 de recherche position at the National Centre for Scientific Research (CNRS, France) in 1994 and served as an associate research scientist in the Department of Dermatology, Columbia University of New York (USA) from 1999 to 2003. Thereafter, Dr Djabali served as an assistant professor in the Department of Dermatology at Columbia University of New York (USA) from 2004 to 2009. Dr. Djabali\u2019s research centers around cellular aging in normal and disease states, with a particular focus on the molecular and cellular pathogenesis of premature aging diseases, such as Hutchinson-Gilford progeria syndrome (HGPS). Her research combines molecular biology, cellular biology, genetics, and proteomics to identify signaling pathways associated with cellular aging to develop preventive strategies to delay and\/or correct aging processes.\r\n\r\n<hr \/>\r\n\r\n<strong>September 2012: <\/strong>To Tom Misteli, PhD, National Cancer Institute, NIH, Bethesda, MD; Technician Award\r\n\r\nDr. Misteli's laboratory seeks to identify lead compounds for HGPS drug development by screening of large libraries of chemical molecules. The Specialty Award was used to purchase robotic laboratory equipment required for these studies.\r\n\r\nTom Misteli is an internationally renowned cell biologist who pioneered the use of imaging approaches to study genomes and gene expression in living cells. He is a Senior Investigator and Associate Director at the National Cancer Institute, NIH. His laboratory\u2019s interest is to uncover fundamental principles of spatial genome organization and to apply this knowledge to the development of novel diagnostic and therapeutic strategies for cancer and aging. He has received numerous awards including the Gold Medal of the Charles University, the Flemming Award, the Gian-Tondury Prize, the NIH Director\u2019s Award, and an NIH Merit Award. He acts as an advisor for numerous national and international agencies and serves on several editorial boards including <em>Cell. <\/em>He is theEditor-in-Chief of <em>The Journal of Cell Biology <\/em>and of<em> Current Opinion in Cell Biology.<\/em>\r\n\r\n<hr \/>\r\n\r\n<strong>July 2012 (start date September 1, 2012): <\/strong>To Vicente Andr\u00e9s Garc\u00eda, PhD, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain; \u201cQuantification of farnesylated progerin and identification of genes that activate aberrant <em>LMNA<\/em> splicing in Hutchinson-Gilford Progeria Syndrome\u201d\r\n\r\nHutchinson-Gilford progeria syndrome (HGPS) is a rare fatal genetic disorder characterized by premature aging and death at an average age of 13 years. Most HGPS patients carry a mutation in the <em>LMNA<\/em> gene (encoding mainly lamin A and lamin C) that leads to the production of \u2018progerin\u2019, an abnormal protein that retains a toxic farnesyl modification. Experiments with cell and mouse models of HGPS have conclusively demonstrated that the total amount of farnesylated progerin and the ratio of progerin to mature lamin A determine disease severity in progeria and is a key factor for lifespan. Ongoing clinical trials are therefore evaluating the efficacy of drugs that inhibit progerin farnesylation in HGPS patients. The main objective of this project is to develop a method to routinely and accurately quantify progerin expression and its level of farnesylation, and the ratio of progerin to mature lamin A, in cells from HGPS patients. Measurement of these parameters will help assess the effectiveness of drugs targeting progerin farnesylation, as well as that of future strategies devised to inhibit abnormal processing (splicing) of the <em>LMNA<\/em> mRNA, the cause of HGPS in most patients. A secondary objective is to perform pilot studies for the development of a high-throughput strategy to identify mechanisms that activate aberrant <em>LMNA<\/em> splicing.\r\n\r\nVicente Andr\u00e9s obtained his PhD in Biological Sciences from the University of Barcelona (1990). During postdoctoral training at the Children's Hospital, Harvard University (1991-1994) and the St. Elizabeth's Medical Center, Tufts University (1994-1995), he led studies into the role of homeobox and MEF2 transcription factors in processes of cellular differentiation and proliferation; and it was also during this period that he developed an interest in cardiovascular research.\u00a0 His career as an independent research scientist began in 1995 when he was appointed Assistant Professor of Medicine at Tufts. Since then Dr. Andr\u00e9s and his group have studied vascular remodeling during atherosclerosis and post-angioplasty restenosis, and more recently they investigate the role of the nuclear envelope in the regulation of signal transduction, gene expression and cell-cycle activity in cardiovascular disease and aging, with particular emphasis on A-type lamins and Hutchinson-Gilford progeria syndrome (HGPS).\r\n\r\nAfter obtaining a position as a Tenured Research Scientist in the Spanish National Research Council (CSIC), Dr. Andr\u00e9s returned to Spain in 1999 to establish his research group in the Institute of Biomedicine of Valencia, where he worked as a Full Professor. Since 2006, his group has been a member of the Red Tem\u00e1tica de Investigaci\u00f3n Cooperativa en Enfermedades Cardiovasculares (RECAVA). He joined the Centro Nacional de Investigaciones Cardiovasculares (CNIC) in September 2009. In 2010 he was awarded the Doctor Leon Dumont Prize by the Belgian Society of Cardiology.\r\n\r\n<hr \/>\r\n\r\n<strong>July 2012 (start date September 1, 2012): <\/strong>To Dr. Samuel Benchimol, York University, Toronto, Canada: \u201cInvolvement of p53 in the premature senescence of HGPS\u201d\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Benchimol.jpg\" alt=\"\" width=\"150\" height=\"170\" \/>Dr. Benchimol has a long record of accomplishment in the area of p53 function.\u00a0 He will use his expertise to build upon intriguing preliminary data and test novel hypotheses regarding the role of p53 in mediating the premature senescence shown by cells from Hutchinson-Gilford Progeria syndrome (HGPS) patients.\u00a0 The first aim is designed to test the hypothesis that progerin causes replication stress, which in turn elicits a senescence growth arrest, and that p53 acts downstream of the progerin-induced replication stress.\u00a0 This aim is followed by a more mechanistic aim that is designed to determine how progerin and p53 collaborate to elicit a senescence response.\r\n\r\n<hr \/>\r\n<p class=\"justifyleft\"><strong>July 2012: <\/strong>To Tom Misteli, PhD, National Cancer Institute, NIH, Bethesda, MD; Specialty Award Amendment<\/p>\r\nDr. Misteli's laboratory seeks to identify lead compounds for HGPS drug development by screening of large libraries of chemical molecules. The Specialty Award was used to purchase robotic laboratory equipment required for these studies.\r\n\r\nTom Misteli is an internationally renowned cell biologist who pioneered the use of imaging approaches to study genomes and gene expression in living cells. He is a Senior Investigator and Associate Director at the National Cancer Institute, NIH. His laboratory\u2019s interest is to uncover fundamental principles of spatial genome organization and to apply this knowledge to the development of novel diagnostic and therapeutic strategies for cancer and aging. He has received numerous awards including the Gold Medal of the Charles University, the Flemming Award, the Gian-Tondury Prize, the NIH Director\u2019s Award, and an NIH Merit Award. He acts as an advisor for numerous national and international agencies and serves on several editorial boards including <em>Cell. <\/em>He is theEditor-in-Chief of <em>The Journal of Cell Biology <\/em>and of<em> Current Opinion in Cell Biology.<\/em>\r\n\r\n<hr \/>\r\n\r\n<strong>December 2011 (start date March 1, 2012): <\/strong>To Dr. Thomas Dechat, PhD, Medical University of Vienna, Austria; \u201cStable membrane association of progerin and implications for pRb signaling\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Dechat.jpg\" alt=\"\" width=\"150\" height=\"167\" \/>A-type lamins are important structural proteins of the nucleus in mammalian cells. They are the major components of a filamentous meshwork located at the inner surface of the nuclear envelope and provide not only shape and mechanical stability to the nucleus, but are also involved in essential cellular processes such as DNA replication and gene expression. Beside their localization at the nuclear periphery, an additional more dynamic pool of A-type lamins is present within the nuclear interior, which is suggested to be important for proper cell proliferation and differentiation. In the last thirteen years over 300 mutations in the gene encoding A-type lamins have been associated with various human diseases, including the premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS). The molecular disease mechanisms are still poorly understood hampering the development of effective therapeutic strategies. The mutation in the A-type lamin gene associated with HGPS results in the production of a mutant lamin A protein, termed progerin. In contrast to normal lamin A, progerin is stably anchored to the nuclear membrane, which alters the mechanical properties of the nucleus. Our working hypothesis proposes that the membrane-anchored progerin also severely affects the dynamic pool of lamins within the nuclear interior and thus cell proliferation and differentiation.\r\n\r\nOne aim of this project is to identify the mechanisms responsible for anchoring progerin to the nuclear membrane and to find ways to specifically inhibit this membrane anchorage with the prospect of rescuing the dynamic lamin pool and thereby reverting cellular phenotypes associated with HGPS. Previous findings show that this dynamic pool of lamin in a complex with other proteins regulates cell proliferation via the retinoblastoma protein (pRb) pathway. In support of our hypothesis, it was recently shown that in cells from HGPS patients the pRb pathway is indeed impaired. In the second aim of our project we propose to study the effects of progerin on the regulation, dynamics and activities of the mobile, nucleoplasmic lamin A pool and its associated proteins and its impact on pRb signaling at molecular detail. The results of our study are expected to shed light on the disease-causing molecular mechanisms behind HGPS and may help to identify novel drug targets and drugs for more efficient and targeted therapies.\r\n\r\nDr. Dechat received his MSc and PhD in Biochemistry at the University of Vienna, Austria. After a year as PostDoc at the Neuromuscular Research Department of the Medical University of Vienna, he was a PostDoc in the laboratory of Prof. Robert Goldman, Northwestern University, Feinberg Medical School, Chicago, Illinois from 2004-2009, working on the structural and functional characterization of nuclear lamins in health and disease with a main focus on the mechanisms leading to Hutchinson-Gilford Progeria Syndrome due to the expression of progerin. Since 2010 he has been an Assistant Professor at the Max F. Perutz Laboratories, Medical University of Vienna, studying the structural and functional properties of nucleoplasmic A-type lamins and LAP2 during the cell cycle and in various diseases associated with mutations in lamins A\/C and LAP2.\r\n\r\n<hr \/>\r\n\r\n<strong>December 2011 (start date March 1, 2012): <\/strong>to Maria Eriksson,PhD, Karolinska Institute, Sweden; Analyzing the possibility for Progeria\u00a0disease reversal\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/Eriksson.jpg\" alt=\"\" width=\"150\" height=\"124\" \/>In this study Dr. Eriksson's lab plans to usetheir recently developed model for progeria with expression of the most commonLMNA gene mutation in the bone. They have previously shown that suppression ofthe expression of the progeria mutation after progeria skin disease developmentled to an almost complete reversal of the disease phenotype (Sagelius, Rosengardtenet al. 2008). Progeria disease progression will be monitored in the bone tissueat different time points following inhibition of the mutation to analyze thepossibility for disease reversal. Their preliminary results indicate improvedclinical symptoms and give promise towards identifying a possible treatment andcure for this disease.\r\n\r\nDr. Eriksson received her MSc Molecular biology at Ume\u00e5 University, Sweden in1996, and her PhD in Neurology from the Karolinska Institutet in 2001. She wasa postdoctoral fellow at the National Human Genome Research Institute, NationalInstitutes of Health 2001-2003, and has been a PI\/Research group leader andAssistant professor at the Dept of Biosciences and Nutrition at the KarolinskaInstitute since 2003. She is also Associate Professor in Medical Genetics atthe Karolinska Institute. Her research interests include Progeria and geneticmechanisms of aging.\r\n\r\n<hr \/>\r\n<p class=\"justifyleft\"><strong>December 2011 (start date March 1, 2012): <\/strong>To Colin L. Stewart D.Phil, Institute of Medical Biology, Singapore; \"Defining themolecular basis to vascular smooth muscle deterioration in Progeria<\/p>\r\nChildren with Progeria die from cardiovascular disease, either a heart attack or stroke. Over the past decade it has become apparent that a key tissue affected by Progeria is the child's blood vessels. Progeria appears to weaken the muscular wall of the blood vessels by somehow causing the smooth muscle cells to die. This not only may make the vessels more fragile, but also stimulates plaque formation leading to blockage of the vessel.\u00a0 Both outcomes result in the blood vessels failing and, if this is in the heart vessels, this will result in a heart attack.\r\n\r\nColin Stewart and his colleague Oliver Dreesen plan to study how the defective form of the nuclear protein Lamin A (progerin) specificallyaffects the growth and survival of the smooth muscle cells in blood vessels.\u00a0 Using stem cell technology Colin and colleagues were able to derive stem cells from skin cells established from 2 children with Progeria. These patient specific stem cells they were then turned into smooth muscle cells resembling those from blood vessels. Intriguingly these smooth muscle cells produced some of the highest levels of progerin, compared to other cell types, suggesting a possible reason as to why blood vessels are severely affected in Progeria. Smooth muscle cells with progerin showed evidence of damage to the DNA in the cell's nucleus. Colin and Oliver will use these and other cells derived from the stem cells to understand what type of DNA is damaged and what biochemical processes, necessary for the survival of the smooth muscle cells are affected by progerin. By being able to directly study smooth muscle cells recreated from children with Progeria, they hope to identify exactly what goes wrong with the cells so as to develop novel procedures to test new drugs that may eventually help treat affected children.\r\n\r\nColin Stewart received his D. Phil from the University of Oxford where he studied interactions between teratocarcinomas, the forerunners of ES cells, and early mouse embryos. Following postdoctoral work with Rudolf Jaenisch in Hamburg, he was a staff scientist at EMBL in Heidelberg. There he was instrumental in discovering the role of the cytokine LIF in maintaining mouse ES cells. He also initiated his interest in the nuclear lamins and nuclear architecture in development. He continued his studies on the lamins, stem cells and genomic imprinting following relocation to the Roche Institute of Molecular Biology in New Jersey. In 1996 he moved to the ABL research program in Frederick, Maryland and in 1999 was appointed Chief of theLaboratory of Cancer and Developmental Biology at the National Cancer Institute.In the last decade his interests have focused on the functional architecture ofthe cell's nucleus in stem cells, regeneration, aging and disease, particularlywith regard to how the nuclear functions are integrated with cytoskeletal dynamics in development and disease. Since June 2007 he has been senior principal investigator and assistant director at the Institute of MedicalBiology at the Singapore Biopolis.\r\n\r\nOliver Dreesen is currently a Senior Research Fellow at the Institute of Medical Biology in Singapore. After completing his undergraduate degree in Bern, Switzerland, Oliver held research positions at the Pasteur Institute in Paris and the University of California, San Diego. Hereceived his PhD from The Rockefeller University in New York where he studied the structure and function of chromosome ends (telomeres) during antigenic variation in African Trypanosomes. His current research interests focus on the roleof telomeres in human disease, aging and cellular reprogramming.\r\n\r\n<hr \/>\r\n\r\n<strong>September 2011 (start date January 1, 2012): <\/strong>To Dr. Dylan Taatjes, University of Colorado, Boulder, CO: Comparative metabolic profiling of HGPS cells and evaluation of phenotypic changes upon modulation of key metabolites\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/taatjes_dylan.jpg\" alt=\"\" width=\"150\" height=\"94\" \/>Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare and debilitating disease that is caused by mutation in the lamin A protein.\u00a0 Past studies have identified the mutations in lamin A that cause the disease and have evaluated its aberrant function in human cells and in mouse models of HGPS.\u00a0 This information, coupled with genome-wide expression studies comparing HGPS cells with those from unaffected individuals, has dramatically advanced our understanding of this disease.\u00a0 One area that has been neglected in HGPS research is a thorough analysis of the metabolic changes that occur in HGPS cells relative to healthy controls.\u00a0 Metabolic abnormalities accompany many human diseases (e.g. atherosclerosis, diabetes, and cancer), and clinical evaluation of HGPS suggests chronic abnormalities in basic metabolic pathways.\r\n\r\nCellular metabolites represent the biochemicals that\u2014together with proteins and nucleic acids\u2014comprise the entire repertoire of molecules within a cell.\u00a0 As such, metabolic changes are arguably as important as gene expression changes in disease pathogenesis.\u00a0 Indeed, the burgeoning field of \u201cmetabolomics\u201d has already yielded many key discoveries linking <em>single metabolites<\/em> to specific human diseases, including leukemia and metastatic prostate cancer.\u00a0 Therefore, identification of the metabolites and metabolic pathways that are altered in HGPS should provide insight into disease pathogenesis and may uncover entirely new therapeutic strategies.\u00a0 This is especially germane to HGPS, as numerous cell-based and in vivo studies have demonstrated that lamin A mutations do not cause irreversible damage and that cellular HGPS phenotypes, if properly treated, can actually be eliminated.\r\n\r\nUpon completing a comprehensive, comparative screen of the metabolites present in cells derived from healthy donors and HGPS patients, follow-up biochemical and cell-based assays will establish whether key metabolites identified in the screen can induce HGPS phenotypes in healthy cells, or reverse HGPS phenotypes in diseased cells.\u00a0 Consequently, this study will not only reveal how HGPS-associated lamin A mutations affect global metabolic pathways in human cells, it will also begin to evaluate whether targeting these pathways represents an effective approach for therapeutic intervention.\r\n\r\nThe Taatjes lab combines expertise in biochemistry, proteomics, and cryo-electron microscopy to study the fundamental mechanisms that regulate human gene expression.\u00a0 The lab also implements genome-wide and metabolomics approaches to help link mechanistic findings with physiological consequences.\u00a0 Metabolomics studies in the Taatjes lab, in conjunction with mechanistic studies with a p53 isoform that causes accelerated aging, serve as a basis for this HGPS study.\r\n\r\n<hr \/>\r\n\r\n<strong>June 2011 (start date January 1, 2012): <\/strong>to Jan Lammerding, PhD, Cornell University\u2019s Weill Institute for Cell and Molecular Biology, Ithaca, NY; Vascular smooth muscle cell dysfunction in Hutchinson-Gilford Progeria Syndrome\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/JanLammerding.jpg\" alt=\"\" width=\"150\" height=\"217\" \/>Hutchinson-Gilford progeria syndrome (HGPS) is caused by mutations in the gene encoding lamins A and C.\u00a0 Children with HGPS develop hair loss, bone defects, loss of fat tissue, and other signs of accelerated aging before succumbing to stroke or myocardial infarctions in their early teens. Post-mortem studies reveal a dramatic loss of vascular smooth muscle cells in the larger blood vessels of HGPS patients. Vascular smooth muscle cells are critical for the normal function of blood vessels, and loss of vascular smooth muscle cells may constitute the driving force behind the lethal cardiovascular disease in HGPS.\r\n\r\nWe have previously demonstrated that skin cells from HGPS patients are more sensitive to mechanical stress, resulting in increased cell death when subjected to repetitive stretch. In this project, we will test whether an increased sensitivity to mechanical stress is also responsible for the progressive loss of vascular smooth muscle cells in HGPS, as large blood vessels are exposed to repetitive vessel strain with each heartbeat. Combined with impaired replenishment of the damaged cells, the increased mechanical sensitivity could lead to the progressive loss of vascular smooth muscle cells and the development of cardiovascular disease in HGPS.\r\n\r\nTo study the effect of mechanical stress on vascular smooth muscle cells in vivo, we will use surgical procedures to locally increase blood pressure or to create vascular injuries in large blood vessels and then compare the effect on survival and regeneration of vascular smooth muscle cells in in a mouse model of HGPS and in healthy controls. Insights gained from these studies will yield new information on the molecular mechanisms underlying the cardiovascular disease in HGPS and may offer new clues into the development of therapeutic approaches.\r\n\r\nDr. Lammerding is an Assistant Professor at Cornell University in the Department of Biomedical Engineering and the Weill Institute for Cell and Molecular Biology. Before moving to Cornell University in 2011, Dr. Lammerding worked as an Assistant Professor in the Department of Medicine at Harvard Medical School\/Brigham and Women\u2019s Hospital and served as a Lecturer at the Massachusetts Institute of Technology. The Lammerding laboratory is studying subcellular biomechanics and the cellular signaling response to mechanical stimulation, with a particular focus on how mutations in nuclear envelope proteins such as lamins can render cells more sensitive to mechanical stress and affect their mechanotransduction signaling. Insights gained from this work can lead to a better understanding of the molecular mechanism underlying various laminopathies, a diverse group of diseases including Hutchison-Gilford progeria syndrome, Emery-Dreifuss muscular dystrophy and familial partial lipodystrophy.\r\n\r\n<hr \/>\r\n\r\n<strong>December 2010 (start date April 1, 2011): <\/strong>To Robert D. Goldman, PhD, Northwestern University Medical School, Chicago, IL; A Role for B-type Lamins in Progeria\r\n\r\nThe A and B-type nuclear lamins are proteins located within the cell\u2019s nucleus. These proteins form separate, but interacting structural networks within the nucleus. The lamins are essential for determining the size, shape, and mechanical properties of the nucleus; and they provide an intranuclear scaffold for organizing chromosomes. We have discovered that when one lamin network is altered by a mutation leading to a malfunction, the other is also altered. Although the typical and atypical forms of Hutchinson Gilford Progeria Syndrome are caused by different mutations in the nuclear lamin A gene, we have found that the B-type lamin networks in progeria patients\u2019 cells are also abnormally altered. The B-type lamins are expressed in all somatic cells from fertilization onward, and they are known to be important in regulating many nuclear functions including DNA replication and gene transcription. Yet little attention has been paid to the lamin B isoforms and their roles in progeria. In this proposal our goal is to determine the effects of the expression of progerin, the most frequently encountered mutant form of lamin A, and other atypical progeria lamin A mutations on the expression, structure and function of the B-type lamins. Our preliminary studies suggest that changes in the B-type lamin networks are important mediators of the cellular pathology in HGPS, because of their interactions with A-type lamins. We will examine changes in the B-type lamins in progeria patient cells and their relationships to cell growth defects and premature senescence. We will also investigate the effects of farnesyltransferase inhibition on the expression, modification and stability of the B-type lamins. This is important as B-type lamins are normally stably farnesylated. These proposed studies are particularly timely given the ongoing clinical trials involving progeria patients utilizing drugs that inhibit protein farnesylation. Our studies promise to provide new insights into the molecular mechanisms responsible for the premature aging of cells in patients with this devastating disease. The results of our investigations should reveal insights into additional potential targets to consider in the development of new therapies for HGPS patients.\r\n\r\nRobert D. Goldman, PhD, is the Stephen Walter Ranson Professor and Chairman of the Department of Cell and Molecular Biology at Northwestern University\u2019s Feinberg School of Medicine in Chicago.\u00a0 Dr. Goldman received his PhD in biology from Princeton University and carried out postdoctoral research at the University of London and at the MRC Institute of Virology in Glasgow.\u00a0 He served on the faculties of Case Western Reserve University, Carnegie-Mellon University and was a Visiting Scientist at the Cold Spring Harbor Laboratory prior to joining Northwestern.\u00a0 He is widely recognized as an authority on the structure and function of the nucleoskeletal and cytoskeletal intermediate filament systems.\u00a0 In the early 1980s he became fascinated with the discovery that lamins were the nuclear form of intermediate filaments.\u00a0 Since that time, his research laboratory has shown that the nuclear lamins are determinants of the size and shape of the nucleus and that they are critically important factors in the disassembly and reassembly of the nucleus during cell division. His research group has further demonstrated that the lamins assemble into a molecular scaffold within the cell\u2019s nucleus required for DNA replication, transcription and chromatin organization.\u00a0 In recent years his interest in the lamins has focused on the impact of lamin A mutations that give rise to the premature aging disease Hutchinson Gilford Progeria Syndrome and other atypical forms of progeria.\u00a0 This has led his research into determining the roles of lamins in chromosome organization, in regulating the epigenetic modifications of chromatin and in cell proliferation and senescence.\r\n\r\nDr. Goldman is a Fellow of the American Association for the Advancement of Science (AAAS), and has been the recipient of Ellison Medical Foundation Senior Scholar and NIH MERIT Awards. He is a prolific writer, has edited numerous volumes for the Cold Spring Harbor Laboratory Press and serves as Associate Editor for the FASEB Journal and Molecular Biology of the Cell. He has been elected to numerous positions in scientific societies including the Board of Directors of the AAAS, the Council and President of the American Society for Cell Biology, and was President of the American Association of Anatomy, Cell Biology and Neuroscience Chairs. He has served on numerous review committees for the American Cancer Society and the NIH, is Director of the Whitman Center of the Marine Biological Laboratory and is frequently invited to organize and speak at international meetings both here and abroad.\r\n\r\n<hr \/>\r\n\r\n<strong>December 2010: <\/strong>To John Graziotto, PhD,\u00a0 Massachusetts General Hospital, Boston, MA; Clearance of Progerin Protein as Therapeutic Target in Hutchinson-Gilford Progeria Syndrome\r\n\r\nHutchinson-Gilford Progeria Syndrome (HGPS) is caused by a mutation in the lamin A gene, which results in the production and accumulation of the mutant disease protein termed progerin.\u00a0 Since this protein accumulates, determining how it is degraded is important from a therapeutic standpoint.\u00a0 The focus of this work is to determine the cellular clearance pathways responsible for degrading the progerin protein.\u00a0 Using this information, we hope to be able to manipulate those pathways to facilitate progerin clearance, with the goal of enhancing current or future therapies for HGPS.\r\n\r\nDr. Graziotto is a Postdoctoral Fellow in the Department of Neurology at Massachusetts General Hospital.\u00a0 He is currently working in the laboratory of Dr. Dimitri Krainc.\u00a0 A major focus of the lab is the study of neurodegenerative disorders in which mutant proteins accumulate and form aggregates.\u00a0 The laboratory studies the clearance mechanisms of these proteins in order to identify modifiers of these pathways which could lead to future targets for treatment.\r\n\r\n<hr \/>\r\n\r\n<strong>December 2010 (Start date April 1, 2011):<\/strong> To Tom Glover PhD, U Michigan, Ann Arbor, MI; \u201cIdentifying Genes for Progeria and Premature Aging by Exome Sequencing\u201d.\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/glover_m_0_0.jpg\" alt=\"\" width=\"150\" height=\"125\" \/>\u201cProgeria\u201d describes a number of disorders which exhibit different aspects of premature aging or segmental progeria.\u00a0 These include HGPS and MAD, both with LMNA mutations, and the DNA repair disorders Cockayne and Werner syndromes.\u00a0 In addition, there are a number of cases of \u201catypical\u201d progeria with overlapping but distinct features.\u00a0 PRF has collected cell lines and\/or DNA on 12 such cases of atypical progeria, representing the largest cohort ever assembled.\u00a0 DNAs have been examined for LMNA exon mutations and none were found, and they are currently being tested for ZMPSTE mutations in Dr.Glover\u2019s lab. In addition, they have phenotypes distinct from classic Werner and Cockayne syndromes.\u00a0 Therefore, these individuals have mutations in unique progeria genes.\u00a0\u00a0 Since most such cases are sporadic, this has been a daunting task.\u00a0 However, during the last few years enormous technical progress has been achieved in the area of DNA sequencing.\u00a0 Whole genome exon sequencing, or \u201cexome sequencing\u201d, has been successfully used to identify mutant genes for a number of monogenic traits including, Miller syndrome, Kabuki syndrome, non-specific mental retardation, Perrault syndrome and many others, with numerous other studies in progress including many studies of <em>de novo<\/em> mutations.\u00a0 This is a powerful tool for gene identification and it is predicted that in the next few years, we will understand the genetic cause of most monogenic traits.\r\n\r\nIn view of these technological advances and the availability of similar patients, Dr. Glover hypothesizes that mutations responsible for atypical progeria can be identified by whole exome sequencing of these patient samples.\u00a0 Identifying these mutations is essential to understanding disease etiology, developing effective treatments and in developing knowledge of intersecting and interacting molecular and cellular pathways in the progerias and normal aging.\u00a0 However, this is challenging given that these are apparently all de novo mutations and the phenotypes are heterogeneous. The immediate outcome of this study will be the discovery of 7-15 novel, likely deleterious mutations for each family that are shared by affected family members and may be unique to the family. The joint analysis of these genes across 6-12 families may well reveal instances of distinct deleterious alleles of the same gene, or different defects in the same functional pathway, appearing in multiple families, thus providing the first glimpse of new candidate genes\/pathways for progeria. \u00a0\u00a0 If successful, the impact of findings could be great and be directly relevant not only to the affected patient and, because of overlapping features, to other forms of progeria including HGPS as well as to normal aging.\r\n\r\nDr. Glover is a Professor in the Department of Human Genetics and Pediatrics at the University of Michigan.\u00a0 He is the author of over 120 research publications and book chapters.\u00a0 Dr. Glover has been actively involved in Progeria research for over a decade and has been a member of the PRF Medical Research Committee since its inception in 2004.\u00a0 His laboratory was involved in the research efforts that first identified LMNA gene mutations in HGPS and in demonstrating that farnyslyation inhibitors can reverse nuclear abnormalities of HGPS cells, opening the door to clinical trials.\u00a0 A major interest of his laboratory is the mechanisms and consequences of genome instability in human genetic disease.\u00a0 Current effort s are aimed at understanding the molecular mechanisms involved in producing copy number variant (CNV) mutations in the human genome.\u00a0 These are a common yet only recently recognized form of mutation important in normal human variation and numerous genetic diseases.\u00a0 However, unlike other forms of mutation, it is not fully understood how they are formed and the genetic and environmental risk factors involved.\r\n\r\n<hr \/>\r\n\r\n<strong>December 2010 (start date March 1, 2011): <\/strong>To Yue Zou, PhD, East Tennessee State University, Johnson City, TN; Molecular Mechanisms of Genome Instability in HGPS\r\n\r\nThe objective of this project is to define the molecular basis of replication abnormality and genome instability in Hutchinson-Gilford progeria syndrome (HGPS) cells. HGPS is a dominant premature aging disease and patients of the disease have an average lifespan of only 13 years. The disease is caused by a point mutation at 1822 or 1824 in exon 11 of lamin A gene, which results in sporadic production of a lamin A mutant protein with 50 amino acids internally truncated, called progerin. Lamin A is a major inner component of the nuclear envelope and skeleton of cells and the presence of progerin leads to abnormal nuclear morphology and genome instability in HGPS cells. Interestingly, recent studies showed that progerin is also produced in normal aging individuals and its level appears to increase with age by an average of 3% per year in coronary arteries. This increase is in concordance with many aspects of cardiovascular pathology in both HGPS and geriatric patients, implicating a potentially important role of progerin in aging and aging-related diseases such cancer and cardiovascular diseases.\r\n\r\nWhile the genetic cause of HGPS is known, the molecular mechanisms by which the action of progerin leads to premature aging-associated phenotypes remain far from clear. We and others have recently demonstrated that HGPS has a phenotype of genome instability caused by cellular accumulation of DNA double-strand breaks (DSBs). DSB accumulation is also a common cause of systemic aging. We also found that <em>Xeroderma Pigmentosum<\/em> group A (XPA) mislocalizes to DSB sites in HGPS cells, leading to inhibition of DSB repair. Depletion of XPA in HGPS cells partially restores DSB repair. Based on these findings, we hypothesize that the DNA damage accumulation in HGPS is likely due to aberrant activities at replication forks which generate unrepairable DSBs, leading to early replication arrest or replicative senescence. Given the fact that HPGS cells are characterized with early replication arrest and premature replicative senescence, revealing the mechanisms underlying the defective activities at replication forks may hold a key to understand the causes of HGPS phenotypes. The understanding could lead to novel strategies for treatment of the disease by intervening in the disease-causing molecular pathways. On the other hand, it is well known that HGPS patients appear to be cancer-free. Although the mechanism remains unknown, it may be attributed to the premature replicative senescence of HPGS. In this research project, we will determine the molecular basis of DSB accumulation in HGPS with the focus on understanding how DNA damage is produced at replication forks. Next we will determine if progerin interacts with DNA replication factors and how the interaction causes the replication abnormalities.\r\n\r\nDr. Zou is a professor in the Department of Biochemistry and Molecular Biology of Quillen College of Medicine at East Tennessee State University. He received his PhD in Biophysics in 1991 from Clark University. Dr. Zou\u2019s research has mainly focused on understanding the genome instability in cancer and related pathways including DNA repair and DNA damage checkpoints. He has recently become interested in genome instability and DNA damage responses in progeria caused by defective maturation of prelamin A, particularly Hutchinson-Gilford Progeria Syndrome, and his group has made interesting findings on the molecular mechanisms of genome instability in HGPS.\r\n\r\n<hr \/>\r\n\r\n<strong>December 2010 (start date January 1, 2011): <\/strong>To Kan Cao, PhD, University of Maryland, College Park, MD; Rapamycin Reverses Cellular Phenotype and Enhanced Mutant Protein Clearance in Hutchinson Gilford Progeria Syndrome\r\n\r\nDr. Cao\u2019s work will investigate the effect of Everolimus on HGPS cells, alone or in combination with Lanafarnib. This study will allow the evaluation of both the therapeutic potential and the mechanistic basis for such combinatorial therapeutic approach.\r\n\r\nDr. Cao is an Assistant Professor in the Department of Cell Biology and Molecular Genetics at the University of Maryland. \u00a0Dr. Cao\u2019s lab is interested in studying cellular mechanisms in progeria and normal aging.\r\n\r\n<hr \/>\r\n\r\n<strong>June 2010 (start date October 1, 2010): <\/strong>To Evgeny Makarov, PhD, Brunel University, Uxbridge, United Kingdom; Identification of the LMNA Splicing Regulators by Comparative Proteomics of the Spliceosomal Complexes.\r\n\r\nDr. Makarov\u2019s research interests are in the field of precursor messenger RNA (pre-mRNA) splicing. Pre-mRNA splicing is a cellular process in which non-coding sequences (introns) are removed and coding sequences (exons) are joined together to generate mRNA for protein production. Pre-mRNA splicing is somewhat similar to film editing: if it is not done properly, two unmatched scenes may be stitched together in one episode, which would not make sense. In splicing, if exon-intron boundaries (splice sites) are not correctly identified, the wrong mRNA will be produced. From this a faulty protein will be synthesised and this may cause disease. To extend the analogy, a film scenario is dramatically changed by the selection of scenes; by the same token, in a living cell, pre-mRNA can be processed in different ways via the alternative use of different splice sites. This phenomenon is called alternative splicing and allows the production of several proteins from a single gene. Dr. Makarov is currently focused on the study of disease-associated alternative splicing. The major ongoing project is on the study of the ageing-related pre-mRNA splicing of human LMNA gene, encoding lamin A and C proteins, and especially, its aberrant splicing that causes the premature ageing of Hutchinson Gilford Progeria Syndrome patients. The aim is to identify the proteins modulating the specific splicing outcomes which, in turn, are likely to affect the speed of the ageing process. In this respect, the pharmaceutical targeting of the proteins identified in the proposed research -- inhibition of their function by small interacting molecules -- may lead to the discovery of novel drugs capable of slowing the ageing process. The other ongoing projects are: (i) The study of SCLC (small cell lung cancer) associated alternative splicing of actinine-4 pre-mRNA; (ii) The hTERT alternative splicing regulation as a potential cancer therapeutic modality.\r\n\r\nDr. Makarov was born and grew up in Leningrad, USSR, where he also graduated from the Leningrad Polytechnical University, Department of Biophysics, in 1980.\u00a0 He earned his Ph.D. degree in Molecular Biology from the Leningrad Nuclear Physics Institute, Department of Molecular and Radiation Biophysics, USSR in 1986 for the study of molecular mechanisms of protein biosynthesis. When the Iron Curtain was lifted he got an opportunity to go abroad, and worked in the United States for three years from 1990-1993 (Washington University, St. Louis and UC Davis) where he continued the study of RNA processing in bacteria. In 1993 he moved to Europe and began to work at Ecole Normale Sup\u00e9rieure, Paris, France, where he studied the efficiency of translation initiation. At that point he began to think of applying his experimental experience from the study of prokaryotic translation to more complicated, fast developing areas of eukaryotic gene expression. Thus, since 1994, he pursued his research interests in the field of pre-mRNA splicing. In 1997, Dr, Makarov had a rare opportunity to join one of the biggest laboratories in the RNA processing field, the laboratory of Reinhard L\u00fchrmann in Germany, where pioneering work was being done in the isolation of \u00a0the small nuclear ribonucleoprotein particles. His work continued in L\u00fchrmann\u2019s laboratory until 2005, and the emphasis of his research was on the purification and characterisation of the spliceosomes. In 2007, Dr. Makarov was appointed as a lecturer at the Division of Biosciences, Brunel University, West London, where his current research is focused around the disease-associated alternative splicing.\r\n\r\n<hr \/>\r\n\r\n<strong>October 2009: <\/strong>to Jason D. Lieb, PhD, University of North Carolina, Chapel Hill NC; Interactions between genes and lamin A\/progerin: a window to understanding Progeria pathology and treatment<strong>\r\n<\/strong>\r\nHutchinson\u2013Gilford Progeria Syndrome (HGPS) is caused by a mutation in the lamin A gene, resulting in production of a shortened protein called progerin. Lamin A normally plays an important function in maintaining the organization of the cell nucleus, and the mutation that creates progerin may result in a disorganization that leads to changes in gene regulation, and ultimately HGPS. However, it is not known which genes interact with lamin A in normal cells, or with progerin in the cells of HGPS patients. We hypothesize that abnormal binding or dissociation of genes with lamin A or progerin in HGPS cells causes misregulation of genes, ultimately leading to HGPS. To find which genes interact with normal lamin A and progerin across the entire genome, Dr. Lieb will perform a technique called ChIP-seq. First, he aims to identify genes that abnormally bind to or detach from lamin A or progerin in HGPS cells. Second, he will perform ChIP-seq in HGPS cells treated with a farnesyltransferase inhibitor (FTI), which shows partial efficacy in treating HGPS symptoms in mouse models. This experiment will reveal which genes\u2019 interactions remain abnormal even after FTI treatment. The data will allow his team to predict signaling pathways that may be responsible for HGPS and the persistent HGPS symptoms reported in FTI-treated mouse models, and will provide a clue for new drugs and treatments for HGPS patients.\r\n\r\nDr. Lieb is an Associate Professor in the Department of Biology and Carolina Center for Genome Sciences. The projects in his laboratory are united by the scientific goal of understanding relationships between DNA packaging, transcription factor targeting, and gene expression. They use three biological systems: S. cerevisiae (baker's yeast) to address basic molecular mechanisms; C. elegans to test the importance of those mechanisms in a simple multicellular organism; and (3) cell lines and clinical samples to directly interrogate chromatin function in human development and disease. The experiments will be carried out by postdoctoral fellow Dr. Kohta Ikegami, who was trained as a graduate student at the University of Tokyo.\r\n\r\n<hr \/>\r\n\r\n<strong><a name=\"Oct09splice\"><\/a><\/strong><strong>October 2009: <\/strong>To Tom Misteli, PhD, National Cancer Institute, NIH, Bethesda, MD;\u00a0 Identification of small molecule modulators of LMNA splicing\r\n\r\nDr. Misteli and his team are developing novel therapeutic strategies for Progeria. His group\u2019s work focuses on interfering with the production of the progerin protein using highly specific molecular tools and to find novel small molecules to counteract the detrimental effects of progerin in patient cells. These efforts will lead to a detailed cell biological understanding of Progeria cells and bring us closer to a molecularly based therapy for Progeria.\r\n\r\nDr. Misteli is a Senior Investigator at the National Cancer Institute where he heads the Cell Biology of Genomes Group and the NCI Cellular Screening Initiative. He is a member of the NCI Center for Excellence in Chromosome Biology. Dr. Misteli has pioneered technology to analyze the function of genes in living cells and his work has provided fundamental insights into genome function. Dr. Misteli has received numerous national and international awards for his work and he serves in numerous advisory and editorial functions.\r\n\r\n<hr \/>\r\n\r\n<a name=\"aug09\"><\/a><strong>August 2009: <\/strong>to William L. Stanford, PhD, University of Toronto, Canada\r\nInduced-Pluripotent Stem Cells (iPSC) from HGPS patient fibroblasts to elucidate the molecular mechanism associated with diminishing vascular function\r\n\r\niPS cells, or Induced pluripotent stem cells are cells that started out as a mature cell type easily obtained and grown in the laboratory, and are treated with biochemical \u201ccues\u201d that signal the cells\u2019 genetic machinery to turn them into immature stem cells. These stem cells are then given additional biochemical \u201ccues\u201d to mature once again, but not into their original cell type. For example, a skin cell (mature) can be first turned into a stem cell (immature) and then turned into a vascular cell (mature). This cutting edge technology is intensely important for Progeria research, where we cannot obtain live human blood vessel, heart and bone cells of children with Progeria for study. The ability to take a Progeria skin cell, grown easily at the PRF Cell and Tissue Bank, and create a Progeria blood vessel cell, will allow us to study heart disease in Progeria in brand new ways.\r\n\r\nThese cells will be valuable for the purpose of banking and distribution to members of the Progeria research community for basic studies and drug development. Dr. Stanford will develop multiple Progeria iPS cells to model Progeria vascular disease stem cells (VSMC), which are seriously depleted in Progeria.\r\n\r\nDr. Stanford is a Canada Research Chair in Stem Cell Bioengineering & Functional Genomics, and Associate Professor & Associate Director of the Institute of Biomaterials & Biomedical Engineering at the University of Toronto. He is also the co-Scientific Director of the Ontario Human iPS Cell Facility. His laboratory is focused on basic and applied research in stem cell biology, tissue engineering and modeling human disease using mouse mutagenesis and patient-specific iPS cells.\r\n\r\n<hr \/>\r\n\r\n<strong>July 2009: <\/strong>to Jakub Tolar, University of Minnesota, Minneapolis, MN\r\nCorrection of human progeria induced pluripotent cells by homologous recombination\r\n\r\nDr. Tolar\u2019s lab has shown that allogeneic cellular therapy with mesenchymal stem cells can prolong survival in the Progeria mouse model, suggesting that cellular therapy can be of benefit to children with Progeria. However, the children have abnormal DNA repair and as such are expected to experience significant toxicities with the chemoradiotherapy needed for engraftment of cells from unrelated donors. Therefore, Dr. Tolar will limit such toxicity by developing genetically corrected cells from the Progeria children themselves, combining the novel concept of iPS cells from Progeria patients with the emerging technology for gene correction mediated by zinc finger nucleases. In this manner he aims to establish a platform for clinical translation of safer stem cell gene therapy with progeny cell types of iPS cells as a definitive treatment for children with Progeria.\r\n\r\nDr. Tolar is an Assistant Professor and attending physician at the University of Minnesota in the Divisions of Pediatric Hematology-Oncology and Pediatric Blood and Marrow Transplantation. Dr. Tolar's research focuses on the use of bone marrow-derived stem cells and gene therapy for correction of genetic diseases and improving outcome of blood and marrow transplantation.\r\n\r\n<hr \/>\r\n\r\n<strong>September 2008 (start date January 2009): <\/strong>To Kris Noel Dahl, PhD, Carnegie Mellon University, Pittsburgh, PA\r\n\u201cQuantification of progerin recruitment to membranes\u201d\r\n\r\nHutchinson-Gilford Progeria Syndrome (HGPS) arises from an abnormal association of a mutant form of a structural nuclear lamin protein, progerin with the nuclear membrane. However, the nature of this increased association has not been determined. In this project, Dr. Dahl and her collaborators will quantify the differences in membrane association of normal lamin A and progerin using purified proteins and purified membranes. With this system, they can precisely quantify the strength of the protein-membrane interaction, determine physical changes that the membrane undergoes in contact with the protein and examine protein orientation at the interface. Also, this purified system will allow them to manipulate different variables such as membrane composition and solution charge. Some of the hypotheses to be examined are the role of the lipid tail and the charge cluster retained on progerin versus the native lamin A and the effects on membrane interaction.\r\n\r\n<img class=\"alignright\" src=\"https:\/\/www.progeriaresearch.org\/assets\/images\/medical_images\/dahl.jpg\" alt=\"\" width=\"100\" height=\"133\" align=\"left\" hspace=\"3\" vspace=\"3\" \/>Prof. Kris Noel Dahl is an Assistant Professor in the Departments of Chemical Engineering and Biomedical Engineering at Carnegie Mellon University. She obtained her PhD in Chemical Engineering at the University of Pennsylvania and did a Postdoctoral Fellowship in the Department of Cell Biology at Johns Hopkins Medical School. Dr. Dahl's group focuses on the mechanical properties of the nucleus from the molecular to the multicellular level. HGPS is one of several disease types in which mutations and molecular reorganization leads to unique nuclear mechanical properties.\r\n\r\n<hr \/>\r\n\r\n<strong>January 2008: <\/strong>To Bryce M. Paschal, PhD, University of Virginia School of Medicine, Charlottesville, VA\r\nNuclear Transport in Hutchinson-Guilford Progeria Syndrome\r\n\r\nAs a principle component of the nuclear lamina, lamin A contributes structural plasticity to the nuclear envelope membrane, provides attachment sites for chromatin, and organizes nuclear pore complexes in the membrane. Given this arrangement, we are exploring how defects in the nuclear lamina observed in Hutchinson-Guilford Progeria Syndrome (HGPS) affect the structure and function of the nuclear pore complex. These studies are designed to provide insight into how changes in nuclear architecture contribute to changes in gene expression in HGPS through transport-based mechanisms.\r\n\r\nDr. Paschal is Associate Professor of Biochemistry and Molecular Genetics at the University of Virginia School of Medicine where he is a member of the Center for Cell Signaling and the UVA Cancer Center. Dr. Paschal has a longstanding interest in the pathways responsible for intracellular transport.\r\n\r\n<hr \/>\r\n\r\n<strong>October 2007: <\/strong>To Michael A. Gimbrone, Jr., M.D., in collaboration with Guillermo Garcia-Cardena, Ph.D. and Belinda Yap, Ph.D., Center for Excellence in Vascular Biology, Brigham and Women\u2019s Hospital, Boston, MA\r\n\r\n\u201cEndothelial Dysfunction and the Pathobiology of Accelerated Atherosclerosis in Hutchinson-Gilford Progeria Syndrome\u201d\r\n\r\nHutchinson-Gilford Progeria Syndrome (HGPS) affects multiple organ systems in various ways, but perhaps its most serious manifestations are in the cardiovascular system, where it results in an unusually severe and accelerated form of atherosclerosis, leading to fatal heart attacks or strokes at an early age. The heart and blood vessels are lined by a transparent, single-cell-thick membrane, consisting of vascular endothelial cells (ECs), which normally forms Nature\u2019s container for blood; pathologic changes in this vital lining, collectively termed \u201cendothelial dysfunction\u201d, are now recognized as critical to the development of vascular diseases, such as atherosclerosis. The purpose of our proposed studies is to determine how the mutant protein progerin, which accumulates in the nuclei of cells in HGPS, influences the structure and function of ECs, potentially leading to endothelial dysfunction. To explore this question, we have created an <em>in vitro<\/em> model system, in which the mutant protein progerin is expressed in cultured human ECs, and have begun to explore the pathologic consequences, utilizing a combination of high-throughput genomic analyses, and molecular structure-function studies. Our preliminary data indicate that progerin accumulation in human ECs leads to marked changes in their nuclear structure, and, importantly, various molecular manifestations of endothelial dysfunction. The latter include the expression of leukocyte adhesion molecules and soluble mediators that have been shown to be associated with the development of atherosclerosis. Our studies promise to provide mechanistic insights into the vascular pathologies of HGPS, and hopefully will lead to novel strategies for its effective treatment.\r\n\r\nDr. Gimbrone is a Professor of Pathology at Harvard Medical School (HMS) and Chairman of Pathology at the Brigham and Women\u2019s Hospital (BWH). He also is Director of the BWH Center for Excellence in Vascular Biology. He is an elected member of the National Academy of Sciences (USA), the Institute of Medicine, and the American Academy of Arts and Sciences. His laboratory is devoted to the study of the vascular endothelium and its role in cardiovascular diseases such as atherosclerosis. Dr. Garcia-Cardena is an Assistant Professor of Pathology, HMS, and Director of the Systems Biology Laboratory in the Center for Excellence in Vascular Biology. Dr. Yap is a postdoctoral fellow in Dr. Gimbrone\u2019s laboratory.\r\n\r\n<hr \/>\r\n\r\n<strong>May 2007: <\/strong>To Thomas N. Wight, PhD, Benaroya Research Institute, Seattle, WA\r\nThe use of a mouse model of HGPS to define the influence of Lamin AD50 expression on vascular extracellular matrix production and the development of vascular disease.\r\n\r\nThe extracellular matrix (ECM) is comprised of molecules that surround cells and act as both structural support and a means for a cell to communicate with its neighbors.\u00a0During the development of atherosclerosis these molecules change and drive the development of the plaque, a process that takes decades in most humans.\u00a0In Hutchinson Gilford Progeria Syndrome (HGPS) this process is drastically accelerated and the specific changes in ECM are not fully understood.\u00a0We therefore propose to study the effect that the HGPS gene has on changes in a group of ECM molecules, called proteoglycans, which are known to play a significant role in atherosclerotic plaque development.\u00a0To do this we will study a mouse model of HGPS developed in the laboratory of Dr. Francis Collins at the NIH, which develops vascular disease.\u00a0Our previous investigations using this mouse have shown accumulation of a proteoglycan-rich ECM in diseased regions of the major arteries.\u00a0In addition to studying proteoglycans in the vessels of these mice fed a high fat diet, we will also take cells from the vessels to grow in petri dishes, which will allow us to more closely examine the specific effect of the HGPS gene on vascular smooth muscle cell ECM.\u00a0Ingrid Harten, a doctoral student in the Department of Pathology at the University of Washington will be working with Dr. Wight on this project. These studies will help to identify possible ways in which the mutant form of Lamin A found in HGPS can regulate the expression of proteoglycans in ways that lead to the development of accelerated atherosclerosis in children with HGPS.\r\n\r\nDr. Wight is a Research Member at the Benaroya Research Institute at Virginia Mason and an Affiliate Professor of Pathology at the University of Washington, where he was a professor from 1988 to 2000.\u00a0He received his PhD from the University of New Hampshire in 1972.\u00a0He is a past awardee of an American Heart Established Investigatorship, has served on NIH and AHA study sections, and currently is on the editorial board of four scientific journals.\u00a0Dr. Wight's research program focuses on the cell biology and pathology of connective tissue.\u00a0Specific interests include cell-extracellular matrix interactions with emphasis on the role of proteoglycans and associated molecules in the regulation of cell behavior, particularly in relation to cardiovascular disease.\r\n\r\n<hr \/>\r\n\r\n<strong>March 2007: <\/strong>To Jemima Barrowman, PhD, Johns Hopkins School of Medicine, Baltimore, MD; Fundamental Mechanism of Lamin A Processing: Relevance to the Aging Disorder HGPS\r\n\r\nHGPS is caused by a mutation in the gene encoding lamin A.\u00a0Normally, lamin A undergoes a transient series of biochemical modifications to its C-terminus, including the addition of a lipid (farnesyl) and a carboxyl methyl group.\u00a0Ultimately, the modified C-terminal tail is cleaved off to generate the final form of lamin A.\u00a0The mutation which causes HGPS prevents cleavage of the tail, resulting in a permanently farnesylated and methylated form of lamin A called progerin.\u00a0A number of studies suggest that blocking the addition of the farnesyl lipid to lamin A by a drug (farnesyl transferase inhibitor; FTI) may provide a therapeutic strategy for progeria.\u00a0In this proposal, we will investigate the possibility that the permanent retention of the carboxyl methyl group may also contribute to progerin\u2019s toxic cellular effects.\u00a0If so, drugs that inhibit carboxyl methyaltion could also be considered as a potential therapeutic option for progeria.\u00a0We will also investigate the possibility that progerin may mimic lamin B, a permanently farnesylated relative of lamin A, thereby competing for lamin B binding partners at the nuclear membrane.\r\n\r\nDr. Barrowman is a Postdoctoral Researcher in the Department of Cell Biology at The Johns Hopkins School of Medicine working in the laboratory of Dr. Michaelis.\u00a0Dr. Michaelis is a Professor in the Department of Cell Biology at Johns Hopkins School of Medicine with a long-term interest in the cellular machinery that modifies farnesylated proteins.\u00a0Her lab has made important contributions in documenting the potential benefits of using farnesyl transferase inhibitors (FTI\u2019s) to inhibit progerin\u2019s toxic cellular effects.\r\n\r\n<hr \/>\r\n\r\n<strong>August 2006: <\/strong>To Zhongjun Zhou, PhD, University of Hong Kong, China<strong>\r\n<\/strong><em>Stem cell therapy of Laminopathy-based Premature Aging\r\n<\/em>\r\nStem cells are the cells that can self-renew and differentiate into a variety of different cell types. They are important because they replace the worn-out cells in the body and maintain the functional integrity of our body. The various tissues in our bodies are rapidly renewed by stem cells and it is common that stem cells decline in aged people. We hypothesize that potential of stem cells in HGPS patients are compromised and cannot provide enough new cells for the renewal of various tissues, therefore leading to accelerated ageing processes. In this project, Dr. Zhou will use a mouse model for HGPS to test if the number and the functions of stem cells in HGPS mice are declined and whether stem cells (bone marrow) derived from healthy mice will rescue the ageing phenotypes in HGPS mice. He will also investigate how the stem cells are affected in HGPS. This work directly tests the feasibility of a potential therapeutic strategy for laminopathy-based premature aging.\r\n\r\nDr. Zhou is an Associate Professor in the Department of Biochemistry and Faculty of Medicine at the University of Hong Kong and obtained his PhD in Medical Biochemistry from Karolinska Institute, where he also performed his postdoc training in the Institute\u2019s Department of Medical Biochemistry and Biophysics. HI group\u2019s main focus of research is on molecular mechanism of laminopathy-based premature ageing. In collaboration with groups in Spain and Sweden, they have made a Zmpste24 deficient mouse to serve as a mouse model for HGPS. They found that unprocessed prelamin A and truncated prelamin A found in HGPS compromise the recruitment of checkpoint response\/repair proteins to damaged DNA, therefore leading to defective DNA repair which in turn contributes to accelerated ageing. Currently, they are investigating if stem cells are affected in HGPS and testing in mice if bone marrow transplantation could rescue, at least partially, the premature ageing phenotypes.\r\n\r\n<hr \/>\r\n\r\n<a name=\"aug06\"><\/a><strong>August 2006: <\/strong>To Michael Sinensky, PhD, East Tennessee State University, Johnson City, TN <em>Effect of FTIs\u2019 on the Structure and Activity of Progerin<\/em>\r\n\r\nHutchinson-Gilford Progeria Syndrome (HGPS) arises from a novel mutation in the gene encoding the protein prelamin A. Normally, prelamin A undergoes a series of biochemical alterations which allow it to form a part of a structure in the nucleus called the nuclear lamina. The mutant prelamin A formed in HGPS (called progerin) is defective in the last of these biochemical alterations leading to accumulation of an intermediate molecule bearing a lipid group referred to as farnesyl . Compounds, called FTIs, which block the formation of this lipid bearing version of progerin have been postulated to be of therapeutic use in the treatment of HGPS. In this proposal we describe tests of the hypothesis that progerin exhibits novelties in its molecular structure that are secondary to adding farnesyl, particularly addition of phosphate. This hypothesis will be tested as will the effects of FTIs on these postulated additions of phosphate\r\n\r\nDr. Sinensky is Professor and Chair in the Department of Biochemistry and Molecular Biology at East Tennessee State University\u2019s Quillen College of Medicine. Between 1987 and 1994 his laboratory, then located at the University of Colorado Health Sciences Center, demonstrated that farnesylation of prelamin A occurred and was the first step in a proteolytic maturation pathway for the molecule. This work grew out of efforts to understand the mechanism of regulation of cholesterol biosynthesis which has also been a significant part of our research program. Since relocating in 1995 to TN, his main research interests have been in the in vitro reconstruction of the prelamin A processing pathway.\r\n\r\n<hr \/>\r\n\r\n<strong>June 2006: <\/strong>To Jan Lammerding, PhD, Brigham and Women's Hospital, Cambridge, MA\r\n<em>The role of nuclear mechanics and mechanotransduction in Hutchinson-Gilford Progeria syndrome and the effect of farnesyltransferase inhibitor treatment<\/em>\r\n\r\nHutchinson-Gilford Progeria Syndrome (HGPS) is caused by mutations in the gene encoding lamin A\/C. Dr. Lammerding recently demonstrated that cells lacking lamin A\/C are mechanically more fragile and have increased cell death and decreased protective cellular signaling in response to mechanical stimulation. Abnormal mechanical sensitivity in response to blood flow and vessel expansion could render blood vessels more susceptible to atherosclerosis, the leading cause of death in HGPS. Furthermore, increased sensitivity to mechanical stress could also contribute to bone and muscle abnormalities seen in HGPS patients. In this project, Dr. Lammerding will conduct a series of experiments to evaluate if cells from Hutchinson-Gilford Progeria syndrome patients are more susceptible to damage through mechanical stimulation. In addition, Dr. Lammerding.s experiments will test if treatment with farnesyl-transferase inhibitors (FTI), a promising new drug for HGPS, can reverse the mechanical deficiencies in HGPS cells and thus lead to a reversal of some of the tissue-specific disease phenotypes.\r\n\r\nDr. Lammerding is an Instructor at Harvard Medical School serving in the Department of Medicine at Brigham and Women's Hospital. His areas of interest include subcellular biomechanics and the cellular signaling response to mechanical stimulation. In particular, he is focusing on how mutations in nuclear envelope proteins such as lamin can render cells more sensitive to mechanical stress and affect their mechanotransduction signaling. Insights gained from this work can lead to a better understanding of the molecular mechanism underlying laminopathies, a diverse group of diseases including Emery-Dreifuss muscular dystrophy, HGPS, and familial partial lipodystrophy.\r\n\r\n<hr \/>\r\n<p align=\"left\"><strong><a name=\"jun06\"><\/a>June 2006: <\/strong>To Tom Misteli, PhD, National Cancer Institute, NIH, Bethesda, MD\r\n<em>Molecular Therapy Approaches for HGPS via correction of pre-mRNA Splicing<\/em><\/p>\r\nDr. Misteli and his team are developing novel therapeutic strategies for progeria. His group\u2019s work focuses on interfering with the production of the progerin protein using highly specific molecular tools and to find novel small molecules to counteract the detrimental effects of the progerin protein in patient cells. These efforts will lead to a detailed cell biological understanding of progeria cells and bring us closer to a molecularly based therapy for progeria.\r\n\r\nDr. Misteli is a Senior Investigator at the National Cancer Institute where he heads the Cell Biology of Genomes Group. He is a member of the NCI Center for Excellence in Chromosome Biology. Dr. Misteli has pioneered technology to analyze the function of genes in living cells and his work has provided fundamental insights into genome function. Dr. Misteli has received numerous national and international awards for his work and he serves in numerous advisory and editorial functions.\r\n\r\n<hr \/>\r\n\r\n<strong>June 2005: <\/strong>To Lucio Comai, PhD, University of Southern California, Los Angeles, CA <em>Functional Analysis of Hutchinson-Gilford Progeria Syndrome<\/em>\r\n\r\nDr. Comai hypothesizes that expression of the mutant Lamin A protein progerin (that causes Progeria) results in premature aging and cardiac disease as a consequence of altered composition and function of Lamin A-containing complexes within the nucleus. To test this hypothesis, he will seek to identify cellular factors that differentially interact with lamin A and progerin. These studies will provide critical information on the molecular defects of Progeria, as we work toward developing treatments at the cellular level.\r\n\r\nDr. Comai is Associate Professor of Molecular Microbiology & Immunology at the USC Keck School of Medicine, and a member of the Keck School\u2019s Institute for Genetic Medicine, Norris Comprehensive Cancer Center and Research Center for Liver Diseases.\r\n\r\n<hr \/>\r\n\r\n<strong>June 2005: <\/strong>To Loren G. Fong, PhD, University of California, Los Angeles, CA<em>; New Mouse Models to Study the Cause of Hutchinson-Gilford Progeria Syndrome<\/em>\r\n\r\nSince the discovery of the Progeria gene mutation more than 2 years ago, efforts have gone on in several laboratories to create a mouse that produces the \"bad\u201d lamin A (progerin) made in Progeria. Dr. Fong and his colleagues have succeeded in doing this, and now will investigate the effects of mouse progerin on the growth and metabolic properties of cells, the development of atherosclerosis, bone abnormalities and lipodystrophy in the whole animal, and finally to test whether any abnormalities can be reversed by farnesyl transferase inhibitors, at present the leading candidates for treatment of Progeria.\r\n\r\nDr. Fong is an Assistant Adjunct Professor at UCLA, and has joined forces with Dr. Stephen Young, a May 2005 PRF grantee, to tackle this important scientific and medical problem.\r\n\r\n<hr \/>\r\n\r\n<strong>January 2005: <\/strong>To Dr. Karima Djabali, PhD, Columbia University, New York, NY; <em>Defining progerin dominant negative effects on the nuclear functions in HGPS cells<\/em>\r\n\r\nDr. Djabali will conduct a fascinating series of experiments aimed at demonstrating the direct relationship of the genetic defect in Hutchinson Gilford Progeria Syndrome to numerous important binding partners in order to characterize the biological basis of disease in Progeria. This work will provide the basic data needed to lead to potential treatments.\r\n\r\nDr. Djabali is Assistant Professor at the Department of Dermatology at the Columbia University Medical School. She has been involved in molecular genetic studies of genetic related disease, and the fields of molecular biology, cell biology, biochemistry and proteomics.\r\n\r\n<hr \/>\r\n\r\n<strong>December 2004: <\/strong>To Robert D. Goldman, PhD and Dale Shumaker, PhD, Northwestern University Medical School, Chicago, Illinois\r\n<em>The Effects of the Major Mutation on Human Lamin A's Function in DNA Replication<\/em>\r\n\r\nDrs. Goldman and Shumaker seek to determine the molecular basis by which the Progeria gene mutations alter nuclear function to cause the premature aging effects seen in children with Progeria. This will shed light on the basic mechanisms responsible for the age-related disorders in the children, information critical to determining ways to combat the progression of the disease.\r\n\r\nStephen Walter Ranson Professor and Chairman of Cell and Molecular Biology at Northwestern University Medical School, Dr Goldman's research has focused on the dynamics of nuclear lamins during cell cycle, examining the relationship between their structure and function. He is an NIH member of Molecular Approaches to Cell Functions and Interactions and serves on the Human Embryonic Stem Cell Advisory Board for the Juvenile Diabetes Foundation. He has worked as an instructor and director in cell and molecular biology at the Marine Biological Laboratory, Woods Hole, Massachusetts.\r\n\r\nDr. Shumaker is a postdoctoral fellow of Cell and Molecular Biology at Northwestern, and has worked with Dr. Goldman studying nuclear lamins since 2001.\r\n\r\n<hr \/>\r\n\r\n<a name=\"#BMT\"><\/a><strong>August 2004 (Start date January 2005): <\/strong>To Stephen Young, PhD, for his project entitled \"Genetic Experiments in Mice to Understand Progeria\".\r\nThe aim of this research project is to use mouse models to build an intellectual foundation for designing appropriate therapies for Hutchinson-Gilford Progeria Syndrome caused by the accumulation of a mutant prelamin A (frequently called \"progerin\") within cells. Dr.Young's laboratory will create a mouse model of Progeria and use that model to understand how the genetic change in Progeria leads to heart disease. As concluded from the <strong>BMT workshop<\/strong>, the study of mouse models is a critical next-step in the process to discover treatments and the cure for Progeria. Dr. Young writes, \"During the past few years, we have created several animal models to explore lamin A\/C biology...We are absolutely convinced that thorough analyses of these mouse models will yield insights relevant to the design of therapies for HGPS.\r\n\r\nDr. Young is a Senior Investigator at the J. David Gladstone Institutes, Professor of Medicine at UCSF, and Staff Cardiologist at the San Francisco General Hospital. Dr. Young will direct and oversee the performance of all the proposed studies. Dr. Young is experienced in using genetically modified mice in biomedical research. His research group has generated and examined more than 50 lines of transgenic mice and more than a 20 gene-targeted mice. In recent years, Dr. Young has studied posttranslational protein modifications, and in particular the postisoprenylation processing steps. During the past few years, his laboratory has generated knockout mice for farnesyltransferase, Zmpste24, Icmt, and Rce1, and prenylcysteine lyase.\r\n\r\n<hr \/>\r\n\r\n<a name=\"A04\"><\/a><strong>April 2004: <\/strong>To Monica Mallampalli, Ph D, and Susan Michaelis, PhD: \u201cStructure, Location and Phenotypic Analysis of Progerin, the mutant form of prelamin A in HGPS\u201d\r\nThis project aims to define the structure of progerin (the abnormal protein in HGPS), develop a cell culture system that allows them to study localization of progerin; and generate progerin-specific antibodies and aptamers for the analysis of function and distribution of progerin in cells and tissues of HGPS patients. Understanding progerin structure and determining how progerin gives rise to the disease state will help reveal the molecular mechanism of HGPS, facilitating rational approaches for the development of treatments.\r\n\r\nDr. Mallampalli is a Postdoctoral Researcher in the Department of Cell Biology at The Johns Hopkins School of Medicine with Dr. Michaelis, Professor in Cell Biology Biophysics at The Johns Hopkins School of Medicine.\r\n\r\n<hr \/>\r\n\r\n<a name=\"7\"><\/a><strong>September 2003 : <\/strong>To Thomas W. Glover, Ph.D. for the project entitled, \" Role of Lamin A Mutations in Hutchinson-Gilford Progeria Syndrome\"<strong>\r\n<\/strong>This project addresses the question of why mutations in lamin A lead to the Progeria phenotype. Recently, the gene responsible for HGPS was identified, and HGPS joined a group of syndromes - the laminopathies - all of which have an underlying defect in the lamin A\/C gene (LMNA). Virtually all HGPS patients have the same mutation creating an abnormal splice donor site in exon 11 of the LMNA gene. The result of the mis-splicing creates a protein missing 50 amino acids near the C-terminus. The deleted region includes a protein cleavage site that normally removes 18 amino acids including a CAAX box farnesylation site. Our research efforts are now focused on examining the effects of the causative mutation in cell culture models in order to gain a better understanding of the disease and work toward the long-term goal of discovering a cure. To this end, we are examining the effect of mutant lamin A expression on a variety of cellular phenotypes including lamin A localization, cell death, cell cycle, and nuclear morphology. These experiments involve the expression of mutant and normal lamin A from mammalian expression constructs in a variety of cell types, and confirmation by examination of the effects of the native protein in HGPS cell lines. In addition, we are developing an in vitro model for adipogenesis in HGPS, which may provide insight into the lack of subcutaneous fat, and related phenotypes, seen in HGPS patients. Finally, we hypothesize that it may be possible to correct or improve the mutant phenotype by exposing the cells to compounds that inhibit farnesylation. We have obtained a variety of such inhibitors and we are presently examining the effects of these compounds on the HGPS cellular phenotypes.\r\n\r\nDr. Glover is a Professor in the Department of Human Genetics at the University of Michigan with research interests in the molecular basis of human genetic disease and chromosomal instability. He is the author of over 120 research publications and book chapters. His laboratory has worked extensively on chromosome instability at fragile sites and has identified and cloned a number of human disease genes, most recently a gene responsible for hereditary lymphedema, and collaborated in the identification of the lamin A gene responsible for Hutchinson-Gilford Progeria.\r\n\r\n<hr \/>\r\n\r\n<a name=\"D03\"><\/a><strong>December 2003: <\/strong>To Joan Lemire, <strong>PhD: \u201cDeveloping a smooth muscle cell model for the study of Hutchinson-Gilford Progeria Syndrome: Is aggrecan a significant component of the phenotype?\u201d<\/strong>\r\nThis project aims to understand the mechanism by which progerin leads to alterations in connective tissues, and most importantly to cardiovascular disease. Children with HGPS die from myocardial infarction, congestive heart failure, and strokes. Aggrecan is a component of connective tissue, and is dramatically elevated in fibroblasts from HGPS patients. Dr. Lemire hypothesizes that this aggrecan overexpression is not limited to fibroblasts and that the arterial smooth muscle cells will also produce aggrecan, which could contribute significantly to this narrowing of the arteries in HGPS. If proven correct, preventing or reversing the lumenal narrowing through aggrecan manipulation may delay the onset of cardiovascular symptoms.\r\n\r\nDr. Lemire is Assistant Professor at Tufts University and recently obtained an NIH-funded grant supporting research in the role of decorin in HGPS.\r\n\r\n<hr \/>\r\n\r\n<a name=\"D032\"><\/a><strong>December 2003:<\/strong> To W. Ted Brown, MD, PhD, FACMG: \u201cDominant Negative Mutation Effects of Progerin\u201d\r\nTo find a potential treatment for HGPS, the mechanism by which the mutated form of lamin A protein, progerin, leads to the disease must be understood. Progerin appears to have a <em>dominant negative mutation;<\/em> it takes on new functions and produces negative, unwanted effects on cellular functions. Dr. Brown hypothesizes that progerin binds to a key nuclear protein, to which lamin A normally does not bind, and this abnormal binding causes detrimental effects. The project focuses on characterizing this unusual binding to help explain how the mutation leads to HGPS.\r\n\r\nDr. Brown is Chairman of the Department of Human Genetics and Director of the George A Jervis Clinic at the New York State Institute for Basic Research. He is a world expert on Progeria, having studied the syndrome for the past 25 years. His cell banking of a number of Progeria cell lines, and his studies contributed to the eventual identification of LMNA mutations in Progeria.\r\n\r\n<hr \/>\r\n\r\n<a name=\"5\"><\/a><strong>May 2002: <\/strong>To Associate Professor Anthony Weiss at the University of Sydney\r\nTitle of project: Candidate Molecular Markers for Hutchinson-Gilford Progeria Syndrome\r\n\r\nProject Description: Accurate diagnosis of Hutchinson-Gilford Progeria Syndrome (HGPS) requires a reliable marker. We have used glyean detection to describe gp200 and identified key overexpressed transcripts that are excellent candidates for HGPS markers in cultured fibroblasts. This one-year project will allow us to use proteomics to identify gp200 and real time RT-PCR methods for examining a leading transcribed candidate marker hgpg200. We will improve the sensitivity of our published gp200 assay, expand the utility of specific transcript analysis, and develop a sensitive assay to facilitate marker detection.\r\n\r\nThis work is important to children with HGPS. (1) It will aid early and accurate diagnosis. (2) This project marks the first time that this combination of proteomics and microarrays\/real time RT-PCR tools is used to explore the molecular features of HGPS. (3) We will identify key molecules that distinguish HGPS. Their identification will provide us with information on the molecular biology and biochemistry of HGPS. (4) By the end of year 1, we expect to provide an assay that can be reliably considered, beyond the current grant, in small biopsy samples and buccal cells taken by gentle swabs.\r\n\r\nBiographical Sketch: Tony Weiss is founding Chair of the Molecular Biotechnology Program University of Sydney, Associate Professor of Biochemistry in the School of Molecular and Microbial Biosciences University of Sydney, Honorary Visiting Scientist in Molecular and Clinical Genetics at Royal Prince Alfred Hospital, and Visiting Professor at the National University of Singapore. Tony was given the Roslyn Flora Goulston Prize and an Australian Postgraduate Research Award then made an ARC Postdoctoral Fellow, after which he moved to the USA as a NIH Fogarty International Fellow. He received further awards including a Fulbright Fellowship at Stanford University before returning to Australia as a CSIRO Postdoctoral Scholar to take up a Faculty position at the University of Sydney. He has twice been a Thomas and Ethel Mary Ewing Scholar and was made a Royal Society Exchange Scholar to pursue research studies in the LTK. Tony was recognized by the Australian Society for Biochemistry and Molecular Biology for distinguished contributions to the field of Biochemistry and Molecular Biology and was awarded the Amersham Pharmacia Biotechnology Medal. He also received the David Syme Research Prize and Medal which is awarded for the best original research work in Biology, Chemistry, Geology or Physics, produced in Australia, during the preceding two years.\r\n\r\n<hr \/>\r\n\r\n<a name=\"3\"><\/a><strong>January 2001 (Start date July 2001): <\/strong>To John M. Sedivy, PhD Brown University, Providence, RI; & Junko Oshima, MD, PhD, University of Washington, Seattle, WA, Cloning of the Gene for Hutchinson-Gilford Progeria Syndrome by Somatic Cell Complementation\"\r\n\r\nThe goal of the research project is to identify the gene whose mutation is responsible for the Hutchinson-Gilford Progeria Syndrome (HGPS). The gene for another progeroid syndrome, Werner's syndrome, has recently been identified through genetic studies of several large afflicted families. Unfortunately, this approach cannot be used in the case of HGPS because there are no families with extended HGPS pedigrees. Dr. Sedivy and his collaborator, Dr. Frank Rothman, have instead proposed to identify the HGPS gene by genetic studies of cells obtained from HGPS patients. This approach will take advantage of two recent developments in biotechnology: first, high density cDNA or oligonucleotide microarrays (commonly known as \"Gene Chips\"), which allow the study of numerous genes at one time; and second, retrovirus vector systems, which make it possible to engineer highly efficient transfer of genetic information from cell to cell. The researchers will first attempt to identify gene expression patterns that differentiate HGPS cells from normal cells, and then use the retrovirus vector technology to search for the gene (or genes) in normal cells that can \"cure\" the HGPS cells.\r\n\r\nJohn M. Sedivy is a Professor of Biology and Medicine in the Department of Molecular Biology, Cell Biology and Biochemistry at Brown University. After completing his undergraduate studies at the University of Toronto in 1978, he obtained his PhD in 1984 in Microbiology and Molecular Genetics from Harvard University. After four years of postdoctoral training in somatic cell genetics in the laboratory of the Nobel laureate Philip Sharp at the Massachusetts Institute of Technology he started his independent research career in 1988 on the faculty of Yale University. He was named Presidential Young Investigator in 1990 and received the Andrew Mellon Award in 1991.\r\n\r\nHe moved to Brown University in 1996, where he teaches genetics and supervises a research group working on basic cancer biology and mechanisms of aging of human cells and tissues. He has served and continues to serve on numerous peer review committees for the National Institutes of Health and the American Cancer Society. His laboratory has been continuously funded by the National Institutes of Health, and has maintained a productive publication record in peer reviewed journals. In 2000 John Sedivy was named Director designate of the Center for Genetics and Genomics which is currently being established at Brown University.\r\n\r\n<strong>Frank G. Rothman, PhD, co-investigator<\/strong>\r\n\r\nFrank G. Rothman is Professor of Biology and Provost, Emeritus at Brown University. He received his Ph.D. degree in chemistry from Harvard University in 1955. From 1957-1961, after two years of service in the U.S. Army, he was a postdoctoral research fellow and associate in molecular genetics at M.I.T. From 1961 until his retirement in 1997 he was on the Biology faculty of Brown University. He taught biochemistry, genetics, and molecular biology at all levels. His research on gene expression in microorganisms was continuously funded by the National Science Foundation from 1961 to 1984. He served as Dean of Biology from 1984-1990, and university Provost from 1990-1995. In the late 1980s he carried out research on aging in the roundworm, Caenorhabditis elegans. He taught courses in the Biology of Aging in 1988 and again in 1996. As Professor Emeritus, he has engaged in collaborative studies on the biology of aging, with a focus on Progeria.\"\r\n\r\n<hr \/>\r\n\r\n<a name=\"4\"><\/a><strong>December 2001: <\/strong>(Start date February 2002): To Thomas W. Glover, Ph.D.\r\n\"Genome Maintenance in Hutchinson-Gilford Progeria Syndrome\"\r\n\r\nThe ultimate goal is to understand the basic defect responsible for HGPS. In this project, we will examine specific aspects of genome maintenance in HGPS cells. We will focus on three areas, telomere dynamics, spontaneous mutation rate, and specific.shtmlects of DNA repair. We will quantitatively measure rates of telomere degradation in HGPS fibroblasts by infecting cells with an hTERT (telomerase catalytic subunit) expressing retrovirus, modified to allow for strict control of telomerase expression. In addition, DNA maintenance will be examined to determine if HGPS, like many premature aging syndromes, involves a defect in DNA repair or replication. Studies will include examination of basal p53 levels in HGPS fibroblasts, the ability of HGPS fibroblasts to repair specific DNA lesions using lesion-specific antibodies, and examination of the rate of spontaneous mutations in HGPS fibroblasts. Many of the studies will include telomerase-immortalized fibroblast cell lines so that experiments can be performed without measuring effects caused by the premature senescence of HGPS fibroblasts. The proposed studies have the potential to give concrete answers as to whether the underlying defect in HGPS is due to faulty genome maintenance. Elucidation of cellular phenotypes associated with HGPS will be a valuable tool in determining the defective molecular pathways and, ultimately, in discovering the disease gene(s).\r\n\r\nThomas W. Glover, Ph.D.: Dr. Glover is a Professor in the Departments of Human Genetics and Pediatrics at the University of Michigan, Ann Arbor, MI. His research focus is the molecular genetics of human genetic disorders and studies of chromosome instability and DNA repair. He has succeeded in identifying or cloning a number of human disease genes including those for Menkes syndrome, a common form of Ehlers-Danlos syndrome, and hereditary lymphedema. He has over 100 peer-reviewed scientific publications and has had continuous NIH grant support. He has served on several Editorial Boards and is a grant reviewer for the March of Dimes Birth Defects Foundation and the National Institutes of Health.\r\n\r\nMichael W. Glynn, M.S. , co-investigator, is a senior graduate student pursuing a Ph.D. in Dr. Glover's laboratory in the Department of Human Genetics at the University of Michigan. He has completed qualifying for candidacy, and has finished all class work and teaching requirements. Honors include the James V. Neel Award for academic excellence awarded by the Department of Human Genetics. He is an author on several papers, a book chapter and two patents. Michael received a Masters of Science degree in Microbiology from the University of Connecticut. He went on to supervise the DNA Diagnostic Lab at Yale Medical School under the direction of Dr. Allen Bale.\r\n\r\n<hr \/>\r\n\r\n<a name=\"1\"><\/a><strong>August 1999: <\/strong>To Leslie B. Gordon, MD, PhD\r\n\"The Pathophysiology of Arterioscleros is in Hutchinson-Gilford Progeria Syndrome\"\r\n\r\n<strong>January 2000: <\/strong>To Leslie B. Gordon, MD, PhD\r\n\"The Role of Hyaluronic Acid in Hutchinson-Gilford Progeria Syndrome\"\r\n\r\nDr. Gordon is focusing on the one consistent difference between Hutchinson-Gilford Progeria Syndrome (HGPS) patients and healthy children: the HGPS patients have much higher levels of a particular compound - hyaluronic acid (HA) - in their urine. HA is necessary for life because it helps hold tissue together, but too much of it might be a bad thing. HA concentrations creep up in elderly people, and plaques that build up in the blood vessels of people who die of heart disease are steeped in HA. The children with HGPS have these same plaques throughout their bodies, and that's what plays a major role in causing heart attacks and strokes. The idea that HA contributes to heart disease is not new, but work in this area has been fostered recently by new analytical tools. In this relatively unexplored area of research, Dr. Gordon is trying to follow the trickle of evidence to its source to find out whether the disease grows more severe as HA levels rise and to establish whether the chemical does indeed promote plaque formation. If such a connection were confirmed, it could lead to therapies that fight both Hutchinson-Gilford Progeria Syndrome and cardiovascular disease by lowering HA levels. \"Any treatments that help these children will very likely help millions of people with cardiovascular disease and potentially other problems associated with aging\", says Dr. Gordon.\r\n\r\nDr. Leslie Beth Gordon is an Instructor in Pediatrics at Hasbro Children's Hospital in Providence, Rhode Island and a Research Associate at Tufts University School of Medicine in Boston, Massachusetts, where she conducts her research on HGPS. She completed the combined MD, PhD program at Brown University School of Medicine in 1998, where she achieved the top-ranking category of outstanding in the medical program and became a member of the Sigma Xi Honor Society. . Prior to that, she received her Masters in Science from Brown University in 1991. Her Bachelor of Arts degree from the University of New Hampshire was awarded in 1986.\r\n\r\nDr. Gordon is working in the laboratory of Dr. Bryan P. Toole, Professor of Anatomy at Tufts University School of Medicine. Others assisting in the project are Ingrid Harten M.S., Margaret Conrad, R.N., and Charlene Draleau, R.N[\/vc_column_text][\/vc_column][\/vc_row]\t\t","_et_gb_content_width":"","footnotes":"","_links_to":"","_links_to_target":""},"class_list":["post-1111","page","type-page","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Grants Funded | The Progeria Research Foundation<\/title>\n<meta name=\"description\" content=\"As of April 2018, PRF has provided over $7.7 million to fund 71 grants for Progeria-related research projects performed in 18 states and 14 other countries!\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.progeriaresearch.org\/fr\/grants-funded\/\" \/>\n<meta property=\"og:locale\" content=\"fr_FR\" \/>\n<meta property=\"og:type\" 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