Determining the detailed mechanisms by which variants in the human genome or genes associated with human genetic variants operate to contribute to disease or health/wellness.
News | Variants to Function & Mechanism
Huntingtin turnover: modulation of huntingtin degradation by cAMP-dependent protein kinase A (PKA) phosphorylation of C-HEAT domain Ser2550
Huntington’s disease (HD) is a neurodegenerative disorder caused by an inherited unstable HTT CAG repeat that expands further, thereby eliciting a disease process that may be initiated by polyglutamine-expanded huntingtin or a short polyglutamine-product. Phosphorylation of selected candidate residues is reported to mediate polyglutamine-fragment degradation and toxicity. In this manuscript, CGM Investigators Ihn Sik Seong, Marcy MacDonald and colleagues used deep mass spectrometry-based phosphoproteomics to systematically identify sites in purified huntingtin and in the endogenous protein. The analyses identified as many as 95 total phospho-sites in Huntingtin, including phosphorylation of C-HEAT Ser2550 by AMP-dependent protein kinase (PKA), which was found to hasten huntingtin degradation. This work highlights categories of phosphosites and biological processes that regulate huntingtin degradation that are relevant to HD pathogenesis and merit further study.
Read more in Human Molecular Genetics
June 21, 2023
Publication
CGM Primary Investigator
Long-term effects of l-serine supplementation upon a mouse model of diabetic neuropathy
Deoxysphingolipids (1-deoxySLs) are neurotoxic sphingolipids associated with obesity and diabetic neuropathy (DN) and have been linked to severity of functional peripheral neuropathies. L-serine supplementation can reduce 1-deoxySL accumulation and improve insulin sensitivity and sensory nerve velocity, but long-term outcomes have not yet been examined. In this work published by CGM investigator Florian Eichler and colleagues, a preclinical model of diabetic neuropathy was treated oral l-serine and longitudinally quantified the extent of functional neuropathy progression. Functional neuropathy and sensory modalities were significantly improved in the treatment group well into advanced stages of disease, however, structural assessments revealed prominent axonal degeneration, apoptosis and Schwann cell pathology, suggesting that neuropathy was ongoing. Thus, despite significant functional improvements, L-serine does not prevent chronic degenerative changes specifically at the structural level, pointing to other processes such as oxidative damage and hyperglycemia that may have additional pathological effects in DN.
Read more in Journal of Diabetes and its Complications
June 21, 2023
Publication
CGM Primary Investigator
Heterozygous mutations in SOX2 may cause idiopathic hypogonadotropic hypogonadism via dominant-negative mechanisms
Pathogenic SRY-box transcription factor 2 (SOX2) variants typically cause severe ocular defects within a SOX2 disorder spectrum that includes hypogonadotropic hypogonadism. In this work published by CGM associate member Ravi Balasubramanian, CGM senior associate member Stephanie Seminara, and CGM investigator Bill Crowley, exome-sequencing data from a large, well-phenotyped cohort of patients with idiopathic hypogonadotropic hypogonadism (IHH) was mined for pathogenic SOX2 variants. They identified 8 IHH individuals harboring heterozygous pathogenic SOX2 variants with variable ocular phenotypes, going on to determine that Sox2 is highly expressed in the hypothalamus of adult mice and colocalized with kisspeptin 1 (KISS1) expression, and suppression of mouse SOX2 protein increased the levels of human kisspeptin, which has previously been invoked in IHH. These data suggest that pathogenic SOX2 variants contribute to both anosmic and normosmic forms of IHH, and highlights the necessity of SOX2 screening in IHH genetic evaluation irrespective of associated ocular defects.
Read more in JCI Insight.
Proteasomal pathway inhibition as a potential therapy for NF2-associated meningioma and schwannoma
Neurofibromatosis 2 (NF2) is an inherited disorder caused by bi-allelic inactivation of the NF2 tumor suppressor gene. NF2-associated tumors, including schwannoma and meningioma, are resistant to chemotherapy, often recurring despite surgery and/or radiation, and have generally shown cytostatic response to signal transduction pathway inhibitors, highlighting the need for improved cytotoxic therapies. In this manuscript by CGM investigator Vijaya Ramesh and colleagues, data from previous high-throughput drug screening in NF2 preclinical models was leveraged to identify a class of compounds targeting the ubiquitin-proteasome pathway (UPP) that may have utility in NF2. Through a series of elaborate investigation of these UPP targeting agents in vitro and in vivo, the group found that treatment delayed tumor growth, suggesting a therapeutic potential. This important work in preclinical models lays the groundwork for use of these drugs as a promising novel treatment strategy for NF2 patients.
Read more in Neuro-Oncology
CHIPping away at cardiovascular disease
Clonal hematopoiesis of indeterminate potential (CHIP), a condition defined by a set of aging-related genetic mutations in blood cells, is associated with an increased risk of several conditions. A team led by CGM PI Pradeep Natarajan and colleagues from Centro Nacional de Investigaciones Cardiovasculares, Stanford University, and Vanderbilt University explored the relationship between CHIP and atherosclerosis in the peripheral arteries. Individuals with mutations in DNA damage repair genes had an increased risk, and mouse data indicated that such mutations may drive increased aortic plaque size and accumulation of macrophages within plaques.
Read more in Nature Cardiovascular Research.
Development of an oral treatment that rescues gait ataxia and retinal degeneration in a phenotypic mouse model of familial dysautonomia.
Familial dysautonomia (FD) is a rare neurodegenerative disease caused by a mutation in the gene encoding for the Elongator complex protein 1 (ELP1). This mutation leads to a reduction of ELP1 protein, mainly in the nervous system. Due to the crucial function of ELP1 in neuronal development and survival, FD patients exhibit many neurological symptoms, including retinal degeneration and inability to coordinate movements. In our recently published study, the Slaugenhaupt and Morini lab describes the optimization of an oral treatment for FD that restores the expression of functional ELP1 protein in every tissue, including brain, and rescues retinal degeneration and motor coordination in a mouse model of FD.
Faculty | Variants to Function & Mechanism
Christopher D. Anderson, MD, MMSc
Associate Neurologist, Massachusetts General Hospital
Associate Professor of Neurology, Harvard Medical School
Dr. Anderson is a Neurocritical Care physician with research expertise in the medical genetics of complex diseases, specifically ischemic and hemorrhagic stroke. His career research goal is to use computational, genetic, and epidemiologic tools to derive new information about the mechanisms underlying cerebrovascular disease, and to use this information to drive improvement in stroke care through the identification of novel treatment targets and implementation of precision strategies for primary and secondary prevention.
Christopher D. Anderson, MD, MMSc
Associate Professor of Neurology, Harvard Medical School
Raghu R. Chivukula, MD, PhD
Assistant Physician, Massachusetts General Hospital
Assistant Professor of Medicine, Harvard Medical School
We are currently most interested in identifying and mechanistically dissecting genetic disorders affecting the biogenesis, trafficking, and function of subcellular compartments (organelles) in specialized cells of the lungs. We aim to apply an understanding of such rare diseases both to uncover new cell biology and to develop novel therapeutic approaches which target fundamental, initiating steps in pulmonary diseases.
Raghu R. Chivukula, MD, PhD
Assistant Professor of Medicine, Harvard Medical School
Melina Claussnitzer, PhD
Investigator, Massachusetts General Hospital
Associate Professor of Medicine, Harvard Medical School
The Claussnitzer lab pioneers Variant-to-Function (V2F) strategies for metabolic diseases.
Melina Claussnitzer, PhD
Associate Professor of Medicine, Harvard Medical School
Susan L. Cotman, PhD
Assistant in Neuroscience, Massachusetts General Hospital
Assistant Professor of Neurology, Harvard Medical School
The Cotman laboratory’s research is focused on understanding the role of the endosomal-lysosomal system in human disease, with a particular emphasis on NCL (Batten disease), the most common cause of neurodegeneration in childhood that also more rarely affects adults.
Susan L. Cotman, PhD
Assistant Professor of Neurology, Harvard Medical School
Mark J. Daly, PhD
Chief, ATGU, Massachusetts General Hospital
Associate Professor of Medicine, Harvard Medical School
The Daly Lab focuses on computational approaches to understanding the genetics of human disease using integrative genomics approaches. The lab has extensive experience in linkage and association analysis, with a focus on developing statistical methods for the design and interpretation of association studies, and applying these approaches specifically to major common disease areas such as neuropsychiatric disease, inflammatory bowel and autoimmune diseases, and diabetes.
Mark J. Daly, PhD
Associate Professor of Medicine, Harvard Medical School
Erin C. Dunn, MPH, ScD
Associate Investigator, Massachusetts General Hospital
Associate Professor, Harvard Medical School
Our research seeks to understand the drivers of both mental illness and mental wellbeing across the lifespan. Much of our work has focused on the social and biological underpinnings of depression and anxiety among women, children, adolescents, and other vulnerable populations, including racial/ethnic minorities and people of low socioeconomic status.
We study a range of biological factors and processes contributing to mental health—including the role of genetic variation and epigenetic mechanisms—as well as biological markers of future risk, such as markers captured in children’s primary (or baby) teeth.
We study multiple social factors, including the role of early life environmental exposures and stressors such as childhood adversity, on mental health.
Erin C. Dunn, MPH, ScD
Associate Professor of Psychiatry, Harvard Medical School
Florian Eichler, MD
Director, Center for Rare Neurological Diseases, Massachusetts General Hospital
Professor of Neurology, Harvard Medical School
Our laboratory at MGH explores the relationship of mutant genes to specific biochemical defects and their contribution to neurodegeneration. To develop novel treatments, our laboratory assesses the consequences of disease causing genes.
Florian Eichler, MD
Professor of Neurology, Harvard Medical School
Hilary K. Finucane, PhD
Assistant in Investigation, Massachusetts General Hospital
Assistant Professor of Medicine, Harvard Medical School
Our group develops and applies new statistical and computational methods for analyzing biological data. Our main focus is on integrating genetic data about disease with molecular data about cell types and biological processes to learn about the causes of disease. We are based at the Broad Institute and Massachusetts General Hospital.
Hilary K. Finucane, PhD
Assistant Professor of Medicine, Harvard Medical School
Jose C. Florez, MD, PhD
Chief, Endocrine Division and Diabetes Unit, Massachusetts General Hospital
Professor of Medicine, Harvard Medical School
The Florez lab aims to unravel the genetic basis of type 2 diabetes, related metabolic traits and its vascular complications, and provide the rationale for effective, precision-tailored therapies. The overarching goal is to bring the clinical treatment of diabetes and its complications into the new paradigm of molecular medicine, using genomic, metabolomic, experimental, physiological and pharmacogenetic approaches.
Jose C. Florez, MD, PhD
Professor of Medicine, Harvard Medical School
Yulia Grishchuk, PhD
Assistant Investigator, Massachusetts General Hospital
Assistant Professor of Neurology, Harvard Medical School
Our research is focused on pre-clinical studies and biomarker discovery for rare pediatric neurologic diseases with high unmet need to enable further development of therapies. Our therapeutic strategies have been focused on use of adeno-associated viral vectors for optimized transduction and transgene delivery to central nervous system, including brain, retina, and optic nerve.
Yulia Grishchuk, PhD
Assistant Professor of Neurology, Harvard Medical School
James F. Gusella, PhD
Research Staff, Massachusetts General Hospital
Bullard Professor of Neurogenetics in the Department of Genetics, Harvard Medical School
Dr. Gusella’s laboratory is currently pursuing collaborative studies at all stages of the genetic research cycle aimed at discovering genes that cause, predispose to or modify neurological and behavioral disorders or caused abnormal development in subjects with balanced chromosomal aberrations and developmental phenotypes, delineating mechanisms of pathogenesis and modifiers in Huntington’s disease, the neurofibromatosis, and autism and exploring the potential for mechanism-based treatments.
James F. Gusella, PhD
Bullard Professor of Neurogenetics in the Department of Genetics, Harvard...
Stephen J. Haggarty, PhD
Associate Neuroscientist, Massachusetts General Hospital
Associate Professor of Neurology, Harvard Medical School
The Haggarty Laboratory seeks to elucidate and modulate the molecular mechanisms underlying neuroplasticity, the brain’s ability to change and reorganize its structure, function, and connections in response to various experiences and learning, for the prevention and treatment of psychiatric and neurological disorders.
Stephen J. Haggarty, PhD
Associate Professor of Neurology, Harvard Medical School
Hailiang Huang, PhD
Assistant Investigator, Massachusetts General Hospital
Assistant Professor of Medicine, Harvard Medical School
The Huang Lab develops and applies cutting-edge statistical genetics and computational techniques to understand the genetic architecture of human complex disorders, especially autoimmune and psychiatric disorders. We are especially interested in novel methods to leverage cross-ancestry genomics data for insights into the disease pathogenesis.
Hailiang Huang, PhD
Assistant Professor of Medicine, Harvard Medical School
Konrad J. Karczewski, PhD
Assistant in Investigation, Massachusetts General Hospital
Instructor in Medicine, Harvard Medical School
Our research is focused on interpreting putative disease variants in common and rare diseases to improve our understanding of human disease and the regulation of the human genome. We do so by assembling and analyzing massive public datasets of genetic variation and functional genomics, building scalable tools and methods to keep pace with the exponential growth of these data types.
Konrad J. Karczewski, PhD
Instructor in Medicine, Harvard Medical School
Rakesh Karmacharya, MD, PhD
Physician Investigator, Massachusetts General Hospital
Associate Professor, Harvard Medical School
Our lab uses experimental approaches at the intersection of chemical biology, genetics and stem cell biology to investigate cellular pathways relevant to schizophrenia, bipolar disorder, autism and related neuropsychiatric disorders. We utilize complementary approaches in specific cellular subtypes and in three-dimensional cerebral organoids generated from human iPSCs. We employ a range of methods including high-content imaging to investigate synaptic biology, multi-electrode arrays to examine neuronal function along with transcriptomic, proteomic and metabolomic experiments. We seek to develop new small molecules that can modulate disease-related processes in patient-derived neurons and develop new therapeutic approaches for targeting cognitive deficits in psychiatric disorders.
Rakesh Karmacharya, MD, PhD
Associate Professor of Psychiatry, Harvard Medical School
W. Taylor Kimberly, MD, PhD
Chief, Division of Neurocritical Care, Massachusetts General Hospital
Associate Professor of Neurology, Harvard Medical School
The Kimberly Lab is committed to reducing the devastating effects of acute brain injury by focusing on translational studies that bridge basic science and clinical research. We believe that therapeutic discovery is not a linear path from fundamental mechanism to new drug, but instead a cycle that requires bi-directional and multidisciplinary integration of basic and patient-oriented research. A presence at each stage of discovery—both directly and through strategic collaboration—is central to our mission to advancing new treatments. Consequently, our laboratory is highly multidisciplinary and collaborative, and our work could not be accomplished without our collaborative partners.
W. Taylor Kimberly, MD, PhD
Associate Professor of Neurology, Harvard Medical School
Ben P. Kleinstiver, PhD
Investigator; Kayden-Lambert MGH Research Scholar 2023-2028, Massachusetts General Hospital
Assistant Professor, Harvard Medical School
The Kleinstiver lab develops genome editing technologies for research applications and for the treatment of human diseases. We develop new approaches and methods to engineer genome editing enzymes, to optimize the properties of CRISPR tools, and to add new functionalities to the editor toolbox, all with the ambition of enabling new treatments for disease.
Ben P. Kleinstiver, PhD
Assistant Professor of Pathology, Harvard Medical School
Jong-Min Lee, PhD
Associate Investigator, Massachusetts General Hospital
Associate Professor, Harvard Medical School
My lab is focused on studying underlying mechanisms and genetic modifiers of neurodegenerative diseases including Huntington’s disease to develop rational therapeutic strategies. For this, we are taking integrated approaches focusing on observations in humans. Major focus areas that are critical to understand pathogenesis and to develop therapeutic strategies include: 1) investigation of molecular mechanisms of tissue specificity, 2) identification of early molecular events, 3) discovery and functional follow-up of genetic modifiers, 4) investigation of genome instability, and 5) developing allele-specific genome editing strategies to address disease-causing mutations.
Jong-Min Lee, PhD
Associate Professor of Neurology, Harvard Medical School
Phil H. Lee, PhD
Assistant in Research, Massachusetts General Hospital
Assistant Professor, Harvard Medical School
We use computational and statistical approaches to understand the genetic bases of complex neuropsychiatric traits and mental disorders. Multivariate pathway analysis forms the backbone of our research on identifying disease risk genes and mechanisms. We also apply multi-modal data analysis integrating genomic and neuroimaging data.
Phil H. Lee, PhD
Assistant Professor of Psychiatry, Harvard Medical School
Marcy E. MacDonald, PhD
Research (Non-Clinical) Staff, Massachusetts General Hospital
Professor of Neurology, Harvard Medical School
Our research, evolving from the discovery of the genetic causes of inherited brain disorders (hereditary spastic paraparesis, neurofibromatosis, neuronal ceroid lipofuscinosis, Huntington’s disease), is now largely focused on the DNA variants that modify the effects of the unstable expanded CAG repeat that causes Huntington’s disease. We do molecular genetic studies with disease and population cohorts and genetically precise model systems. Our goal is to enable timely intervention, diagnosis and disease-management.
Marcy E. MacDonald, PhD
Professor of Neurology, Harvard Medical School
Vamsi K. Mootha, MD
Principal Investigator, Massachusetts General Hospital
Professor of Systems Biology, Harvard Medical School
The long-term goals of the Mootha Laboratory are to combine the new tools of genomics and systems biology with classic biochemistry to investigate mitochondrial bioenergetics, evolution, and disease.
Vamsi K. Mootha, MD
Professor of Systems Biology, Harvard Medical School
Patricia L. Musolino, MD, PhD
Physician-Scientist, Massachusetts General Hospital
Assistant Professor of Neurology, Harvard Medical School
The Musolino Laboratory at the Center for Genomic Medicine at Massachusetts General Hospital and Harvard Medical School is a translational neuroscience laboratory focusing on developing gene targeted therapies for inherited inborn errors of metabolism and cerebrovascular disorders that lead to stroke and leukodystrophy.
Patricia L. Musolino, MD, PhD
Assistant Professor of Neurology, Harvard Medical School
Benjamin M. Neale, PhD
Associate Investigator, Massachusetts General Hospital
Associate Professor of Medicine, Harvard Medical School
The Neale lab focuses on uncovering the genetic risk factors of common disease, in particular through international collaboration to diversify the global representation of study participants, as well as the research community involved in such efforts. We develop statistical methods and computational tools to enable efficient and scalable analysis of the growing datasets available in genetic sequencing studies.
Benjamin M. Neale, PhD
Associate Professor of Medicine, Harvard Medical School
Aarno Palotie
Lecturer, Harvard Medical School
Group Leader, Massachusetts General Hospital
Understanding disease genetics using the Finnish founder population
Aarno Palotie
Lecturer, Harvard Medical School Group Leader, Massachusetts General Hospital Understanding...
Roy H. Perlis, MD
Associate Chief for Research, Department of Psychiatry, Massachusetts General Hospital
Professor of Psychiatry, Harvard Medical School
Our lab focuses on developing clinical and genomic predictors of treatment response, and on developing novel therapeutics based on cellular models of brain disease. We use cellular modeling, transcriptomics, clinical phenotyping, and small molecule screening to study psychiatric disorders including schizophrenia, bipolar disorder, and depression.
Roy H. Perlis, MD
Professor of Psychiatry, Harvard Medical School
Vijaya Ramesh, PhD
Neuroscientist, Massachusetts General Hospital
Professor of Neurology, Harvard Medical School
My lab has been primarily working on understanding the pathophysiology of two different inherited neurocutaneous syndromes, Neurofibromatosis 2 (NF2) and Tuberous Sclerosis Complex (TSC). We have collaborative studies with investigators outside MGH for these studies. We also collaborate with Dr. Xandra Breakefield and Dr. Casey Maguire labs for gene therapy studies of NF2 and TSC.
Vijaya Ramesh, PhD
Professor of Neurology, Harvard Medical School
Jonathan Rosand, MD, MSc
J. P. Kistler Endowed Chair in Neurology, Massachusetts General Hospital
Professor of Neurology, Harvard Medical School
The hallmark of our work is the combination of careful clinical characterization of patients with the most rigorous approaches to genetics. We work in partnership with patients and their families to understand the factors that contribute to maintaining vascular brain health across the lifespan. We are a leading contributor to the performance and analysis of high-throughput genome-wide association and sequencing studies in stroke and related traits. At our core, we serve as a training ground for outstanding scientists and clinician-scientists who go on to become world-class leaders in the field. The lab has created a legacy of multidisciplinary teams that are successfully tackling some of the most pressing challenges in brain disease. Among these teams is the International Stroke Genetics Consortium, which we founded in 2007 to bring together the world’s pre-eminent stroke investigators.
Jonathan Rosand, MD, MSc
Professor of Neurology, Harvard Medical School
Jeremiah M. Scharf, MD, PhD
Physician-Scientist, Massachusetts General Hospital
Assistant Professor of Neurology, Harvard Medical School
The Scharf lab investigates the genetic and neurobiological mechanisms of Tourette Syndrome (TS) and related developmental neuropsychiatric disorders that lie at the interface between traditional concepts of neurologic and psychiatric disease, including obsessive compulsive spectrum disorders (OCD/OCSD) and attention-deficit hyperactivity disorder (ADHD). We conduct genetic and clinical research to identify both genetic and non-genetic risk factors that contribute to the predisposition of TS, ADHD, and OCD in patients and families. We hope to identify novel targets for treatment, to understand the course of TS and related conditions at a patient-specific level, and to better predict treatment response.
Jeremiah M. Scharf, MD, PhD
Assistant Professor of Neurology, Harvard Medical School
Ihn Sik Seong, PhD
Geneticist, Massachusetts General Hospital
Associate Professor of Neurology, Harvard Medical School
Seong laboratory is focused on understanding the fundamental mechanism of neurodegenerative diseases and neurodevelopmental disorders using precise genetic disease cells/mice models. Our research into the structural, biochemical, and functional properties of the full-length huntingtin protein continues to aim to understand Huntington’s disease (HD) at its root cause.
Ihn Sik Seong, PhD
Associate Professor of Neurology, Harvard Medical School
Susan A. Slaugenhaupt, PhD
Professor of Neurology (Genetics), Harvard Medical School
Investigator, Massachusetts General Hospital
My research focuses on two neurological disorders, familial dysautonomia (FD) and mucolipidosis type IV (MLIV), as well as the common cardiac disorder mitral valve prolapse (MVP). Our work is focused on gene discovery and therapeutic development, specifically targeting mRNA splicing.
Susan A. Slaugenhaupt, PhD
Professor of Neurology (Genetics), Harvard Medical School
Jordan W. Smoller, MD, ScD
MGH Trustees Endowed Chair in Psychiatric Neuroscience, Massachusetts General Hospital
MGH Trustees Endowed Chair in Psychiatric Neuroscience, Massachusetts General Hospital
Professor of Psychiatry, Harvard Medical School
The focus of Dr. Smoller’s research interests has been:
- Understanding the genetic and environmental determinants of psychiatric disorders across the lifespan.
- Integrating genomics and neuroscience to unravel how genes affect brain structure and function.
- Using “big data”, including electronic health records and genomics, to advance precision medicine.
Jordan W. Smoller, MD, ScD
Professor of Psychiatry, Harvard Medical School
Alexander Soukas, MD, PhD
Associate Professor of Medicine, Harvard Medical School
Associate Professor of Medicine, Massachusetts General Hospital
Aging is the single, greatest contributor to nearly every disease and condition that affects us after our youth. Diabetes, obesity, heart disease, stroke, cancer, osteoporosis, and dementia are all diseases of aging. In the Soukas Laboratory, we endeavor to figure out how things go wrong in the cells of the body in aging, and more excitingly, how to fix what goes wrong. Our findings have the ability to impact not one, but nearly every disease that impacts humankind. We have the major goal of identifying molecular “switches” that can be thrown to turn back the clock on the aging process, promoting healthy aging and staving off aging-associated diseases.
Alexander Soukas, MD, PhD
Associate Professor of Medicine, Harvard Medical School
David A. Sweetser MD, PhD
Pediatrician, Massachusetts General Hospital
Assistant Professor of Pediatrics, Harvard Medical School
The Sweetser Lab has two areas of focus. One is rare disease work. Our work with the Undiagnosed Diseases Network takes a deep dive into phenotyping, evaluations, and genome sequencing, and functional characterization to identify novel genetic disorders. We also have focused projects in Pitt Hopkins syndrome, IQSEC2, and epileptic encephalopathies with Natural History studies and creating patient derived stem cell models. The second area of research seeks to characterize the leukemic stem cell niche and develop targeted cancer therapies.
David A. Sweetser MD, PhD
Assistant Professor of Pediatrics, Harvard Medical School
Michael E. Talkowski, PhD
Associate Investigator, Massachusetts General Hospital
Associate Professor of Neurology, Harvard Medical School
The Talkowski lab integrates molecular and computational genomics methods to study the genetic etiology of disorders affecting prenatal, neonatal, and early childhood development, as well as neurodevelopmental and psychiatric disorders. Our lab is also interested in variant-to-function studies to understand genomic perturbations to regulatory pathways in rare diseases and the applications of emerging technologies to clinical diagnostic screening.
Michael E. Talkowski, PhD
Director, CGM; Associate Professor of Neurology, Harvard Medical School
Miriam Udler, MD, PhD
Assistant Professor, Harvard Medical School
Attending in Endocrinology, Massachusetts General Hospital
Director, MGH Diabetes Genetics Clinic
We focus on advancing precision diagnosis and management of metabolic diseases.
Miriam Udler, MD, PhD
Attending in Endocrinology, Massachusetts General Hospital
James A. Walker, PhD
Assistant in Genetics, Massachusetts General Hospital
Assistant Professor of Neurology, Harvard Medical School
Our research focuses primarily on neurofibromatosis type 1 (NF1), a genetic disorder with an incidence of one in 3,000–4,000 people. Most adults with NF1 develop neurofibromas – benign, but often disfiguring, tumors associated with peripheral nerves.
James A. Walker, PhD
Assistant Professor of Neurology, Harvard Medical School
Vanessa C. Wheeler, PhD
Research Geneticist, Massachusetts General Hospital
Associate Professor of Neurology, Harvard Medical School
Repeat expansion diseases such as Huntington’s disease (HD) are characterized by the instability of their causative repeat mutations. The inherited repeat undergoes further somatic expansion that drives disease pathogenesis. Our lab uses patients and model systems to characterize and uncover the underlying modifiers and mechanisms of repeat instability in order to identify targets for disease-modifying therapies.
Vanessa C. Wheeler, PhD
Associate Professor of Neurology, Harvard Medical School
Wei Zhou, PhD
Assistant investigator, Massachusetts General Hospital
Our lab focuses on developing and applying statistical methods to uncover genetic risk factors for human diseases using large-scale biobanks as well as leveraging high-dimensional omics data to interpret the genetic association discoveries.
Wei Zhou, PhD
Assistant investigator, Massachusetts General Hospital
The Center for Genomic Medicine (CGM) comprises one of the largest and most vibrant hubs of genomic medicine research in the world. The CGM includes 46 faculty collaborating to define the ‘genomic medicine cycle’ – which envisages a genomics community seeking to advance research from basic genomics research to ultimately using genome information for diagnostics and targeted therapeutics. All of our investigators are faculty at Harvard Medical School, and many members of our community are also investigators at the Broad Institute of Harvard and MIT.
