Psychiatric and Neurodevelopmental Genetics Unit (PNGU)

Overview

Psychiatric and neurodevelopmental disorders are common, costly and often disabling conditions that affect individuals throughout their lives. Disability associated with neuropsychiatric disorders exceeds that of other medical illnesses, and psychiatric disorders are also associated with premature mortality. Familial and genetic factors are the most-substantiated risk factors for a broad range of neuropsychiatric disorders.

The Psychiatric & Neurodevelopmental Genetics Unit (PNGU) at Massachusetts General Hospital is working to identify and characterize the genetic basis of these disorders and offer hope for improving treatment and prevention strategies.

Research Team

Jordan Smoller, MD, ScD
Director of the Psychiatric & Neurodevelopmental Genetics Unit

Jordan Smoller, MD, ScD, is a psychiatrist, epidemiologist and geneticist whose research focus has been understanding the genetic and environmental determinants of psychiatric disorders across the lifespan and using big data to advance precision mental health including improved methods to reduce risk and enhance resilience.

Dr. Smoller is the Massachusetts General Hospital Trustees Endowed Chair in Psychiatric Neuroscience, professor of Psychiatry at Harvard Medical School and professor in the Department of Epidemiology at the Harvard School of Public Health in Boston. He is associate chief for research in the Mass General Department of Psychiatry, director of the Center for Precision Psychiatry and director of the Psychiatric and Neurodevelopmental Genetics Unit in the Mass General Center for Genomic Medicine. Dr. Smoller is a Tepper Family MGH Research Scholar and also serves as director of the Omics Unit of the Mass General Division of Clinical Research and co-director of the Mass General Brigham Biobank. He is director of the Mass General Brigham Training Program in Precision and Genomic Medicine, an associate member of the Broad Institute, co-chair of the Cross-Disorder Workgroup of the Psychiatric Genomics Consortium and president of the International Society of Psychiatric Genetics.

Alysa E Doyle, Ph.D.

Dr. Alysa E Doyle is an Associate Professor of Psychology in the Department of Psychiatry at Massachusetts General Hospital and Harvard Medical School, as well as a Director of Research, Learning and Emotional Assessment Program at Mass General.

Alysa E Doyle PhD is a licensed child and adult clinical psychologist trained in psychiatric genetics, developmental psychopathology and pediatric neuropsychology.

er research aims to clarify the complex mechanisms that confer risk for neuropsychiatric illness across the lifespan. Specifically, she is seeking to understand the roles that genomic variation and cognition play in mental health and psychosocial trajectories from youth to young adulthood. This work will inform the translation of emerging genomic discoveries to the child clinical setting for purposes of risk stratification and early intervention.

Tian Ge, Ph.D.

Dr. Ge is Associate Professor of Psychiatry at Harvard Medical School, Director of Data Science in the Massachusetts General Hospital Center for Precision Psychiatry, Faculty in the MGH Center for Genomic Medicine, and Affiliated Scientist at the Stanley Center for Psychiatric Genetics, Broad Institute of MIT and Harvard. Research in the Ge Lab broadly focuses on statistical genetics and neuroimaging genetics.

Stephen J. Haggarty, PhD
Associate Professor of Neurology, Harvard Medical School; Associate Neuroscientist, Massachusetts General Hospital

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. Through pioneering studies leveraging patient-derived stem cell models in conjunction with chemical genomics and systems neuropharmacology, we seek to unravel complex human disease biology and develop innovative mechanism-based targeted therapeutics. In parallel to our research efforts, we are also dedicated to training the next generation of translational neuroscientists whose creativity and insight will revolutionize our understanding of brain health and realize the promise of precision medicine.

Rakesh Karmacharya, M.D., Ph.D.
Associate Professor of Psychiatry at Harvard Medical School and Psychiatrist in the Massachusetts General Hospital

Dr. Karmacharya is working at the intersection of chemical biology and stem cell biology to investigate the cellular-molecular underpinnings of schizophrenia and bipolar disorder. He received an A.B. in Biochemistry from Harvard, an M.S. in Molecular Biophysics from Yale, and an M.D. and a Ph.D. in Biophysics from the Albert Einstein College of Medicine. After his clinical training, he undertook postdoctoral studies in chemical biology under the mentorship of Prof. Stuart Schreiber.

Karestan Chase Koenen, Ph.D.
Institute member at the Broad Institute of MIT and Harvard and a professor of psychiatric epidemiology at the Harvard T.H. Chan School of Public Health

Karestan C. Koenen, Ph.D., a clinical psychologist, epidemiologist, and author is Professor of Psychiatric Epidemiology at the Harvard T.H. Chan School of Public Health where she aims to reduce the population burden of mental disorders through research, training, and advocacy. She is passionate about using science to overcome violence and trauma, which are major preventable causes of health problems globally.

Phil Hyoun Lee, Ph.D.
Associate Professor of Psychiatry at Harvard Medical School and Massachusetts General Hospital

Dr. Lee is a computational geneticist investigating the genetic basis of complex human traits and disorders by developing and applying effective analytic strategies. While the methods and study designs Dr. Lee has developed have been applied to studies of diverse complex traits, the research program over the past six years has focused primarily on psychiatric and neurodevelopmental disorders, including autism spectrum disorders and schizophrenia. Dr. Lee’s long-term goal is to build a computational genomics program that will spearhead translational research in medicine—helping to define biomarkers, clarify diagnostic boundaries, and accelerate the development of personalized interventions and treatment strategies.

Benjamin Neale, Ph.D.

Core Institute Member at Broad Institute, and Co-director, Stanley Center for Psychiatric Research at Broad Institute. Associate Professor at Harvard Medical School and Associate Investigator at Massachusetts General Hospital.

As a statistical geneticist and leader of global genetic analysis projects, Neale is strongly committed to gaining insights into the genetics of common, complex human diseases with a heavy emphasis on severe mental illnesses. Neale’s research focuses on the generation and analysis of large-scale genomic datasets from biobanks around the world.

He and his team develop statistical methods to interpret such data and use AI in the study of mental illness. He has led large-scale international genetic studies of patients with ADHD, autism, age-related macular degeneration, type 2 diabetes, and metabolic disorders. His lab leads the analysis of the ongoing rare variant discovery efforts for schizophrenia and bipolar disorder. Neale’s lab developed Hail, the engine for scalable genetic analysis that is used worldwide for applications such as systematic genetic discovery for all ICD codes in UK Biobank or gnomAD, the world's allele frequency reference. Neale has been instrumental in the development of novel genomic assays including designing the exome chip, psychchip, and blended genome exome product, which have been used to assay millions of human DNA samples.

Aarno Palotie, M.D., Ph.D.
Lecturer, Harvard Medical School
Group Leader, Massachusetts General Hospital

The overall goal of the Palotie group is to improve understanding of the genetic mechanisms underlying common diseases. Much of our work draws on the unique clinical and population-based large sample collections from the Finnish founder population. One of the main focus areas is genetics of neurological, neurodevelopmental and neuropsychiatric traits.

Roy Perlis, MD

Roy Perlis, MD MSc is Associate Chief for Research in the Department of Psychiatry and Director of the Center for Quantitative Health at Massachusetts General Hospital, where he holds the Ronald I. Dozoretz, MD Endowed Chair. He is Professor of Psychiatry at Harvard Medical School and Associate Editor at JAMA's open-access journal, JAMA Network - Open.

Dr. Perlis's research is focused on identifying predictors of treatment response in brain diseases, and using these biomarkers to develop novel treatments. He directs two complementary laboratory efforts, one focused on patient-derived cellular models and one applying machine learning to large clinical databases. These two programs converge in the MGH NeuroBank, one of the largest cellular biobanks in the world for the study of neurodevelopmental and neurodegenerative disorders. The NeuroBank spans more than 400 cell lines associated with detailed clinical phenotypic assessment and links to electronic health records.

Elise B. Robinson, ScD
Institute Member of the Broad Institute of MIT and Harvard; Associate Professor in the Center for Genomic Medicine and Department of Psychiatry, Massachusetts General Hospital

Dr. Robinson’s lab focuses on the genetic epidemiology of behavior and cognition. The lab is interested in using genetic data to understand the biology of neurodevelopmental variation and to study differences within and between neuropsychiatric disorders. Dr. Robinson’s team applies techniques from statistical genetics and epidemiology to investigate how common and rare genetic risk factors for severe neuropsychiatric disorders may differ and develops approaches for examining these questions in large samples. Their research examines genetic influences on human behavioral and cognitive variation and leverages genetic data to illuminate the biological basis of neuropsychiatric disorders.

Jeremiah Scharf, MD, PhD
Assistant Professor of Neurology, Harvard Medical School; Physician-Scientist, Massachusetts General Hospital

Genetic and neurobiological mechanisms of Tourette Syndrome (TS) and related disorders.
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.

Michael Talkowski, Ph.D.
Director, Center for Genomic Medicine, Massachusetts General Hospital

The Talkowski Laboratory is seeking to understand the impact of genomic variation on human disease. We study the genetic etiology of disorders affecting prenatal, neonatal, and early childhood development, particularly autism spectrum disorder (ASD) and related neurodevelopmental and psychiatric disorders. Our group is particularly interested in alterations to the structure of the genome (structural variation) across human populations and its functional consequences in disease.

Wei Zhou, PhD
Assistant Investigator, Massachusetts General Hospital; Assistant Professor, Harvard Medical School

Zhou’s 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.

Administrative and Research Support Team

Kristin Joyce
Assistant to Dr. Smoller

Kristin Joyce has been employed with Massachusetts General Hospital since 1988 having 35+ years of administrative experience. She has been a staff assistant III to Dr. Smoller since June, 2013 and is an integral part of the PNGU team and operations.