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Less than 4 months after the Progeria gene discovery announcement, and with support from the National Institutes of Health’s National Institute on Aging, Office of Rare Diseases, and National Human Genome Research Institute, PRF and NIH held a phenomenally successful, 2nd Hutchinson-Gilford Progeria workshop in the wake of the gene discovery. Fifty-five scientists participated in this 2-day workshop packed with presentations and stimulating discussion on current data and potential new research directions in the wake of the gene discovery.
Senior Advisor to the Director for Translational Research at the National Human Genome Research Institute at NIH. Dr.Austin's work focuses on the implementation of research programs to derive biological insights and therapeutic benefits from the recently completed human genome sequence. Prior to his current position, Dr. Austin was Director of Genomic Neuroscience at Merck Research Laboratories, where he directed target identification and drug development programs on several neuropsychiatric diseases, with a particular focus on schizophrenia in DNA microarray technologies, pharmacogenomics, and molecular histology.
Scott D. Berns, MD, MPH, FAAP
Vice President of Chapter Programs for the March of Dimes, Adjunct Associate Professor of Pediatrics at Brown University School of Medicine, and a Progeria Research Foundation (PRF) Board Member. Previously, Dr. Berns was awarded a White House Fellowship where he served as a Special Assistant to the U.S. Secretary of Transportation. Dr. Berns is a Fellow of the American Academy of Pediatrics and has served on the boards of the Genetic Alliance, National Healthy Mothers, and Healthy Babies Coalition. Dr. Berns has received awards from the American Academy of Pediatrics, National Highway Traffic Safety Administration, and U.S. Secretary of Transportation, Norman Mineta.
W. Ted Brown, MD, PhD, FACMG
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 was an original member of PRF's Board of Directors and Medical Research Committee. As a medical student, Dr. Brown became interested in Progeria and its relationship to aging which led to his initial research studies of abnormalities of DNA repair in Progeria cells. He established an International Progeria Registry, examining some 60 cases within 25 years. His cell banking of a number of Progeria cell lines, and his studies of a set of identical twins, where one was shown to have a rearrangement involving chromosome 1, contributed to the eventual identification of LMNA mutations in Progeria. As a medical geneticist, his research focus has been on Fragile X syndrome and genetics of developmental disabilities.
Judith Campisi, PhD
Senior Scientist at the Lawrence Berkeley National Laboratory and Professor at the Buck Institute for Age Research. Dr. Campisi's research is focused on understanding the molecular and cellular basis for aging, and the role of aging in the development of cancer. She has received several awards for her research contributions and serves on several advisory and editorial boards.
Angela M. Christiano, PhD
Associate Professor, Departments of Dermatology and Genetics & Development and Director of Research, Dept. of Dermatology at Columbia University.
Francis S. Collins, MD, PhD
Director of the National Human Genome Research Institute at NIH. Dr. Collins is responsible for overseeing the human genome project directed at mapping and sequencing the entire human DNA, and determining.shtmlects of its function. The completed sequence was unveiled in April 2003, and all data has been made available to the scientific community. Dr. Collins' research has led to the identification of genes responsible for cystic fibrosis, neurofibromatosis, Huntington's disease and, most recently, Hutchinson-Gilford Progeria Syndrome (HGPS). Dr. Collins is also a member of the Institute of Medicine and the National Academy of Sciences.
Maria Rosaria D'Apice, PhD
Scientist in Prof. Novelli's laboratory of human genetics at Tor Vergata University's School of Medicine, Rome, Italy. Dr. Rosaria's research is focused on the mutational analysis of LMNA gene in Mandibuloacral Dysplasia (MAD) and HGPS. Her goal is to identify genes that cause MAD, in pedigrees that are unlinked to the LMNA locus, as well as, the genes participating in tissue-specific cellular pathways in MAD fibroblasts with LMNA mutation.
Karima Djabali, PhD
Assistant Professor in Dermatology at Columbia University. Dr. Djabali's research interest is the nuclear matrix compartment which affects chromatin organization, gene expression, cell growth and differentiation. Dr. Djabali uses the skin as a model system to understand nuclear matrix constituents and, by combining genetic and proteomic approaches, follows protein expression profiles during cell growth and differentiation. Mis-expression of any of these nuclear matrix proteins severely disrupts the nuclear architecture, chromatin remodeling, and gene expression thereby leading to specific disorders such as certain types of cancer and laminopathies.
Maria Eriksson, PhD
Postdoctoral fellow in the laboratory of Dr. Collins at the National Human Genome Research Institute at NIH. Dr. Eriksson is the lead author on the recent Nature paper that describes the gene defect responsible for HGPS.
Clair A. Francomano, MD
Senior Investigator and Chief, Human Genetics & Integrative Medicine Section, Laboratory of Genetics, National Institute on Aging. Dr. Francomano's laboratory is focused on the creation of mouse models for human diseases caused by mutations in Fibroblast Growth Factor Receptor 3, and the development of in vitro methods to study cartilage and chondrocyte biology. She has also studied the natural history of Marfan Syndrome, Stickler Syndrome, and Ehlers-Danlos syndrome. She is involved in a number of advisory boards and is President of the International Skeletal Dypslasia Society.
Thomas W. Glover, PhD
Senior Investigator, Department of Human Genetics at the University of Michigan. Dr. Glover's research interests are in the molecular basis of human genetic disease and chromosomal instability. His lab is studying the chromosome instability at fragile sites. Dr. Glover's research has identified and cloned a number of human disease genes, including the gene responsible for hereditary lymphedema. Dr. Glover participated in the collaborative effort to identify the lamin A gene responsible for HGPS. He is now addressing the question of why mutations in lamin A lead to the Progeria phenotype.
Michael W. Glynn, MS
Senior doctoral student in Human Genetics at the University of Michigan. He has concentrated on Progeria for his Ph.D. research and was recently awarded a University of Michigan Rackham Graduate Student Fellowship for the coming year to continue his research on HGPS.
Robert D. Goldman, PhD
Stephen 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. Dr. Goldman will be chairing a Novartis Symposium on Nuclear Organization in Development and Diseases.
Stephen Goldman, PhD
Health Science Administrator at the National Heart, Lung and Blood Institute, Division of Heart and Vascular Disease, National Institutes of Health.
Yosef Gruenbaum, PhD
Professor of Genetics and Chair of Genetics, The Hebrew University of Jerusalem. Currently, Dr.Gruenbaum is a Visiting Professor at Northwestern University. His research includes the mechanism of DNA methylation in the eukaryotic cell, and he has a background in material sciences, chemistry, and physics. Recently, he was awarded the Gruss-Lipper fellowship.
Audrey Gordon, Esq
Founding President and Executive Director of The Progeria Research Foundation (PRF), whose mission is to discover the cause and develop treatments and a cure for HGPS. Ms. Gordon is a licensed attorney in Massachusetts and Florida since 1988.
Leslie B. Gordon, MD, PhD
Assistant Professor of Pediatrics at Brown University School of Medicine in Providence, RI and in Anatomy and Cellular Biology at Tufts University School of Medicine in Boston, MA, where she conducts her basic science research on HGPS. She is the Medical Director for PRF and the parent of a child with Progeria. She is also the Principal Investigator for the PRF Cell and Tissue Bank, PRF Medical and Research Database, and the PRF Diagnostics Program.
Stephen C. Groft, PharmD
Director, Office of Rare Diseases, NIH. Dr. Groft has devoted attention to working with patient support groups in their efforts to stimulate research on their diseases. His office has co-sponsored over 380 scientific workshops and symposia with the NIH research Institutes and Centers and patient support groups. He has recently completed an assignment as the Executive Director of the White House Commission on Complementary and Alternative Medicine Policy. He established the Office of Alternative Medicine at NIH and has served with the Department of Health and Human Services as the Executive Director of the National Commission on Orphan Diseases.
Senior undergraduate student at University of California, Irvine. Mr Hagen is focusing his studies on biochemistry and molecular biology. He is also working on HGPS in Dr. Collin's laboratory at the National Human Genome Research Institute.
Gregory Hannon, PhD
Professor, Watson School of Biological Sciences at Cold Spring Harbor Laboratory. Dr. Hannon's research centers on double-stranded RNA-induced gene silencing or RNAi. His work focuses on understanding the biochemical mechanism of this phenomenon. Identification of new elements of the machinery will lead to a deeper understanding of the biological function of RNAi pathways and to the development of better RNAi-based tools for use in mammalian genetics and ultimately to the application of RNAi as a therapeutic approach.
Heather Hardie, MD
Attending Radiologist, Director of Musculoskeletal Imaging at Sturdy Memorial Hospital, Attleboro, MA. Dr. Hardy specializes in Musculoskeletal Imaging at Massachusetts General Hospital in Boston, MA.
Christine J. Harling-Berg, PhD
Assistant Professor of Pediatrics (research) at Brown University Medical School and Memorial Hospital of Rhode Island. Dr. Harling-Berg is an original member of PRF's Medical Research Committee. Her research has focused on developing animal models for studying the immune response to proteins in the brain and elucidating the TH2-biased immune response of brain/immune system interactions. More recently, she has studied the effects of cross-reactive, anti-neuronal antibodies on brain function. Dr. Harling-Berg will be a lecturer at the Marine Biological Laboratories at Woods Hole
Ingrid Harten, MS
Graduate student in the Cell, Molecular and Developmental Biology Program at Tufts University. Ms. Harten's research goals include determining the phenotypic characteristics of HGPS fibroblasts in vitro and what roles they may play in the pathophysiology of disease.
Richard J. Hodes, PhD
Director of the National Institute on Aging (NIA) at NIH, Department of Health and Human Services. The NIA is the principal Federal funding agency for studies of basic, clinical, epidemiological, and social.shtmlects of aging. Dr. Hodes was named Director of the NIA in 1993, but has enjoyed a long career in science at NIH as an investigator in the National Cancer Institute. Dr. Hodes maintains an active research program at NIH, focused on cellular and molecular regulation of the immune response. He is a Diplomate of the American Board of Internal Medicine. Dr. Hodes has been elected to The Dana Alliance for Brain Initiatives, the American Association for the Advancement of Science, and the Institute of Medicine of the National Academy of Sciences.
Dr. Kaleko, PhD, MD
Co-founder of Advanced Vision Therapies, Inc. Dr. Kaleko's work focuses on ocular therapeutics. Dr. Kaleko has directed projects to develop gene transfer vectors for the treatment of hemophilia, cancer, and ocular diseases at Genetic Therapy, Inc. He has also conducted gene therapy research at the Fred Hutchinson Cancer Research Center.
Johanne Kaplan, PhD
Senior Director of Immunotherapy at Genzyme Corporation. Dr. Kaplan has been active in pre-clinical gene therapy and immunotherapy research. Prior to her current position, Dr. Kaplan established an Immunotoxicology Unit within the Department of Experimental Pathology at SmithKline Beecham Pharmaceuticals.
Monica Kleinman, MD
Pediatric Intensivist at Children's Hospital in Boston, MA. Dr. Kleinman is an original member of PRF's Board of Directors and chair of PRF's Medical Research Committee. She is responsible for ensuring review of PRF grant applications and reporting on PRF-funded research to the Board.
Charles A. and Helen B. Stuart Emeritus Professor of Medical Science, in Molec. Microbiol. & Immunol at Brown University. Dr. Knopf is an original member of PRF's Medical Research Committee. He has worked in Francis Crick's laboratory at the MRC Laboratory, Molecular Biology, demonstrating the initiation of nascent polypeptide chains in vitro. He has also worked at the Salk Institute to elucidate steps in intracellular pathways leading to surface expression or secretion of immunoglobulins. At Brown University, his laboratory has cloned a gene and expressed the candidate vaccine antigen of Schistosoma mansoni. More recently, he has co-developed a model system for studying immune responses to antigens introduced into brain behind intact blood-brain barrier and has studied the effects of anti-neuronal antibodies on brain function.
Joan Lemire, PhD
Assistant Professor (research) at Tufts University. Dr. Lemire has recently obtained a grant supporting research in the role of decorin in HGPS. She began HGPS research in Dr. Toole's laboratory at Tufts University. Previously, Dr.Lemire worked at the University of Washington in the labs of Dr. Stephen M. Schwartz and Dr. Thomas N. Wight, studying vascular smooth muscle cell types and splice variants of the vascular proteoglycan versican.
Marc Lewis, PhD
Professor of Psychology at the University of Texas at Austin and Senior Ethnologist for the Organization for Tropical Research and Exploration. He is new to the field, coming via the Cold Spring Harbor Yeast Genetics Course and a Fellowship to the Ellison Foundation Molecular Biology of Aging Course. His research looks at aging using a combination of molecular biology, problem solving, and epidemiology.
Jun Kelly Liu, PhD
Assistant Professor, Department of Molecular Biology and Genetics at Cornell University. Dr. Liu's lab uses the nematode C. elegans to explore two areas of research: 1) how muscle and non-muscle cells derived from the mesoderm choose their specific cell fates during development, and 2) how do various nuclear envelope proteins function during development. Previous research on the nuclear envelope project includes characterizing the function of a nuclear envelope protein YA during Drosophila early embryonic development and elucidating the in vivo functions of lamin and lamin associated nuclear envelope proteins (including LEM domain proteins Emerin and MAN1) during C. elegans development. She is currently investigating the relationship between the nuclear envelope, lamin and ageing using C. elegans as a model system and exploring the possibility of using C. elegans to investigate the cellular and molecular basis of various laminopathies.
Monica Mallampalli, Ph. D.
Postdoctoral Researcher in the Department of Cell Biology at The Johns Hopkins School of Medicine, working with Dr. Susan Michaelis.
Susan Michaelis, PhD
Professor, in Cell Biology Biophysics at The Johns Hopkins School of Medicine. Dr. Michaelis' research focuses on Saccharomyces cerevisiae, and in particular the yeast mating pathway, which provides an ideal model system for dissecting a variety basic cell biological processes common to all eukaryotic cells. Her laboratory uses genetic, biochemical, and cell biological approaches to learn about protein trafficking, posttranslational modification of proteins (including prenylation, proteolytic cleavage, and carboxyl methylation), ER quality control, the ubiquitin-proteasome system, and ABC transporters. Results from her research have been applied to cystic fibrosis, the chemotherapeutic intervention of Ras-based cancers, multidrug resistance of tumor cells mediated by ABC proteins transporters, and most recently laminopathies.
Tom Misteli, PhD
Director of the Cell Biology of Genomes Group at the National Cancer Institute, NIH. Dr. Misteli uses in vivo imaging and computational methods to study nuclear architecture and genome organization in living cells.
Elizabeth G. Nabel
Scientific Director, Clinical Research at the National Heart, Lung and Blood Institute, NIH. Dr. Nabel is interested in the molecular pathogenesis and genetic therapies for vascular diseases. Her laboratory investigates the regulation of vascular smooth muscle cell proliferation and inflammation in the vasculature by cell cycle proteins. More recently, her studies have focused on the role of bone marrow-derived progenitor cells in vascular regeneration as well as clinical studies on the genomics of the vascular disease, restenosis. Prior to joining the NHBLI, Dr. Nabel was the Chief of Cardiology and Director of the Cardiovascular Research Center at the University of Michigan
Nancy L Nadon, PhD
Head the Office of Biological Resources and Resource Development at National Institute on Aging. Responsible for developing new resources to assist the research community in gerontology research, including the aged rodent colonies, aged cell bank, and tissue bank from the aged rodent colony.
Sally Nolin, PhD
Director of the DNA diagnostic laboratory at the New York State Institute for Basic Research in Developmental Disabilities. Dr. Nolan has worked extensively on Fragile X syndrome. She was orignially trained as a cytogeneticist and then a genetic counselor prior to joining IBR.
Giuseppe Novelli, PhD
Professor at Tor Vergata University of Rome. Dr. Novelli's laboratory studies the functional analysis of SNPs (single nucleotide polymorphisms) and the molecular genetics of rare diseases. His laboratory has an interdisciplinary approach to research and combines the fields of human genetics, medical genetics, genomics, and molecular genetics. His laboratory's results in translational research can be applied to molecular diagnosis, presymptomatic and predictive diagnosis, prenatal diagnosis, and pharmacogenetics .
Junko Oshima, MD, PhD
Research Associate Professor at the University of Washington School of Medicine, Department of Pathology. Dr. Oshima has long held interest in the genetic mechanisms of human aging. She collaborated with Dr. Judith Campisi concerning the alteration of gene expression during cellular senescence. She then moved on to study the positional clonings of age-related genetic disorders, Alzheimer disease, and Werner syndrome, which were successfully cloned in collaboration with Dr. George M. Martin. Dr. Oshima's ongoing projects include the International Registry of Werner Syndrome, cellular biological studies of the WRN gene, and the population study of genes involved in the oxidative damage theory of aging.
Darwin J. Prockop, MD, PhD
Professor and Director of the Center for Gene Therapy, Tulane University Health Sciences Center. Dr. Prockop's major interest is in using adult stem cells from bone marrow for cell and gene therapy of a variety of diseases including osteoporosis, Parkinson's disease and Alzheimer's disease. He has also conducted research in the biosynthesis of collagen, structure and function of collagen genes and genetic mutations that cause diseases of bone and cartilage. Prior to his current position, Dr. Prockop was Director of The Center for Gene Therapy at MCP Hahnemann Medical School. He is an elected member of the Academy of Finland, the U.S. Institute of Medicine, and the National Academy of Sciences.
Frank Rothman, PhD
Professor of Molecular Biology, Cell Biology, and Biochemistry (Research) and Provost Emeritus at Brown University. Dr. Rothman is an original member of PRF's Medical Research Committee. His research has included gene-protein relationships and gene regulation in E. coli, followed by studies of the genetics and development of the cellular slime mold D. discoideum. While at Brown University, Dr. Rothman developed a small teaching and research program in the field of Biology of Aging. He has recently done collaborative research on HGPS.
Paola Scaffidi, PhD
Post-doctoral fellow at the National Cancer Institute, NIH. Dr Scaffidi received his PhD from the Open University of London and has worked at Dibit, San Raffaele Scientific Institute, Milan, Italy.
Shepherd H. Schurman, MD
Research Fellow in the Laboratory of Genetics of the National Institute on Aging at NIH. Previously, Dr. Schurman worked at the National Human Genome Research Institute of the NIH as a Research Fellow and Primary Physician on clinical protocol treating Adenosine Deaminase (ADA) deficiency patients with ADA gene transfer into autologous bone marrow stem cells.
Stephen M. Schwartz, MD, PhD
Professor of Pathology and Adjunct Professor of Cardiology and Bioengineering at the University of Washington School of Medicine in Seattle, WA. Dr. Schwartz's laboratory specializes in growth control of vessel wall cells. He is the Principal Investigator of an NIH Program Project entitled "Genomic and Genetic Approaches to Plaque Rupture", a MERIT Grant on "Endothelial Injury in Small Vessels" as well as several RO1 grants. He is also the Director of the Cardiovascular Pathology Training Program at the U.W. Dr. Schwartz serves on several Editorial Boards, and has served on a number of NHLBI Committees, as well as various Committee posts at the University of Washington.
Felipe Sierra, PhD
Head of the Extramural Portfolio on Cell Structure and Function of the Biology of Aging Program at NIA. He handles applications related to the cellular basis of accelerated aging syndromes, including Werner's and will facilitate the majority of applications dealing with HGPS. Dr. Sierra is also involved with the Protein Structure and Function and the Advanced Research Technologies portfolios. Previously, his research focused on dysregulation of signal transduction and gene expression with aging, as well as the role of proteases and phosphatases on this process. Dr. Sierra's career has involved academic and industry positions in Switzerland, Chile and USA. He has served in numerous advisory panels within the NIH system and abroad.
Colin Stewart, PhD
Director of the Cancer and Developmental Biology Laboratory in the ABL-Basic Research Program, which was then incorporated into the NCI in 1999. Dr. Stewart's research interests are centered on mammalian developmental genetics, and the role of the nuclear envelope in development and disease.
Lino Tessarollo, PhD
Principal Investigator, Neural Development Group, Mouse Cancer Genetics Program, and Director of the Gene Targeting Facility at the National Cancer Institute. Dr. Tessarollo's interests include mouse genetics and mouse modeling with particular emphasis on Neurotrophic factors.
Bryan Toole, PhD
Professor of Cell Biology and Anatomy and Member of the Hollings Cancer Center, Medical University of South Carolina. Dr. Toole is a member of PRF's Medical Research Committee, and his laboratory at Tufts University was the initial site of Dr. Leslie Gordon's progeria research. Dr. Toole's laboratory has recently found that the hyaluronan "cocoon" is lacking in fibroblasts from HGPS patients and suggests that loss of cell-associated hyaluronan may be part of the cell senescence program. Hyaluronan physically protects the cell and induces receptor-mediated intracellular signaling, critical for cell survival and for morphogenetic cell behavior during embryogenesis and adult tissue repair. He is a Fellow of the American Association for Advancement of Science and Member of the Editorial Board for The Journal of Biological Chemistry.
Sylvia Vlcek, PhD
Postdoctoral fellow in the laboratory of Dr. Katherine Wilson at the Johns Hopkins University School of Medicine. Dr. Vlcek is investigating the interaction of a novel protein called Lip1 with A-type lamins in the nuclear interior. Previously, she worked with Dr. Roland Foisner at the Vienna Biocenter in Austria where she focused on the functional analysis of the intranuclear lamin A/C binding partner LAP2a in cell proliferation and nuclear assembly.
Huber Warner, PhD
Associate Director at NIA. Dr. Warner is responsible for the Biology of Aging extramural program of grants. Dr. Warner's program has co-sponsored both the original HGPS workshop in 2001, and the current one. He has facilitated two Program Announcements soliciting research proposals on HGPS in 2002 and 2003.
Anthony Weiss, PhD
Professor, endowed Personal Professorial Chair in Biochemistry and founding chair of Molecular Biotechnology at the University of Sydney. Dr. Weiss specializes in the study of connective tissue proteins with emphasis on human elastin. He is using a combination of molecular biology and protein-based tools to explore molecular downstream consequences of DNA changes in HGPS. Prior research includes production of a large synthetic gene able to generate human tropoelastin. Dr. Weiss also has an Honorary Visiting appointment in Molecular and Clinical Genetics at Royal Prince Alfred Hospital and related regional academic positions.
Katherine L. Wilson, PhD
Professor at Johns Hopkins Medical School, Department of Cell Biology. Dr. Wilson's laboratory is studying 'LEM-domain' nuclear membrane proteins, with a special emphasis on emerin.. Her laboratory is studying interactions between emerin and lamin filaments, BAF, transcription and splicing factors, 'anchoring' partners and nuclear actin. The loss of emerin causes Emery-Dreifuss muscular dystrophy (EDMD), a tissue-specific disease that affects the heart, skeletal muscle and tendons. Loss of emerin causes exactly the same disease, EDMD, as do many dominant missense mutations in lamin A. Dr. Wilson and her colleagues hypothesize that emerin and lamin A form ternary complexes required for the assembly or function of many other binding partners in the nucleus.
Howard J. Worman, PhD
Associate Professor of Medicine and Anatomy and Cell Biology at Columbia University College of Physicians and Surgeons. Dr. Worman started his research on the nuclear envelope and nuclear lamina in 1987 as a postdoctoral fellow at Rockefeller University with Nobel Laureate Dr. Günter Blobel. Dr. Worman's contributions to our understanding of the nuclear envelope and lamina include the initial structural characterization of LMNA, the gene that encodes nuclear lamin A and nuclear lamin C, the discovery and cDNA cloning of novel proteins of the inner nuclear membrane and the development of a model for how integral membranes are targeted to the inner nuclear membrane.
Stephen G. Young, MD
Gladstone Institute of Cardiovascular Disease at the University of California. Dr. Young's research interests are in the areas of lipoproteins and atherosclerosis, postranslational processing of prenylated proteins, and gene trapping in ES cells. He is Board Certified in Medicine and Cardiology.
Michael Zastrow, B.A.
Graduate student in the laboratory of Dr. Katherine Wilson, Department of Cell Biology, Johns Hopkins University School of Medicine.
Nanbert A. Zhong, M.D.
Head of the Developmental Genetics Laboratory in the Department of Human Genetics at the New York State Institute for Basic Research in Developmental Disabilities. Dr. Zhong has worked on Fragile X Syndrome and Batten's disease, and has an NIH grant to study protein interactions in NCLs (Batten related diseases).
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