Rakesh Karmacharya

Assistant Professor of Psychiatry
Harvard Medical School
Psychiatric and Neurodevelopmental Genetics Unit

Center for Human Genetic Research
Massachusetts General Hospital
Richard B. Simches Research Center
185 Cambridge Street
Boston, MA 02114
Phone: 617-726-5119
Email: karmacharya@chgr.mgh.harvard.edu

Dr. Karmacharya is a physician scientist who is investigating the cellular and molecular underpinnings of schizophrenia and bipolar disorder. He received his A.B. in Biochemistry from Harvard University, M.S. in Molecular Biophysics and Biochemistry from Yale University and his MD and PhD in Biophysics from Albert Einstein College of Medicine. His graduate studies focused on theoretical studies of the quantum mechanics of proton tunneling in condensed phase, under the mentorship of Professor Steven D. Schwartz.

He did an Internship in Internal Medicine at Mass General, followed by a Residency in Psychiatry in the Mass General-McLean program, where he served as the Chief Resident of the Schizophrenia and Bipolar Disorder Program. After his residency, he undertook postdoctoral studies in the Chemical Biology Program at the Broad Institute of Harvard and MIT, under the mentorship of Prof. Stuart L. Schreiber.

He is currently the Director of Stem Cell Research in the Center for Experimental Drugs & Diagnostics at Mass General, Medical Director of the Schizophrenia and Bipolar Disorder Research Clinic at McLean Hospital and a Physician Scientist in the Chemical Biology Program at the Broad Institute of Harvard and MIT. His current research aims to discover new pathways relevant to disease biology and develop small molecules that can be translated into novel therapies by applying chemical biology approaches.


  • Identification of disease signatures for schizophrenia and bipolar disorder using patient iPSC-derived neuronal cells
    We are generating induced pluripotent stem cells (iPSCs) by reprogramming fibroblasts obtained from patients with schizophrenia, bipolar disorder and matched controls and differentiating the patient iPSCs into cortical and hippocampal neuronal subtypes. We are profiling the patient iPSC-derived neurons using high-content imaging as well as gene-expression studies in the presence of different small molecule perturbations. Our goal is to identify robust cellular signatures that underlie the disease biology of schizophrenia and bipolar disorder, which can then be used in high-throughput screens of small molecule libraries to discover compounds that can normalize/modulate cellular disease signatures.
  • High-throughput small-molecule and RNAi screens of modulators of the Wnt-GSK3-Beta Catenin signaling pathway
    The Wnt pathway plays a major role in neurogenesis and modulation of the Wnt pathway is postulated to be important in the therapeutic effects of lithium. The goal of this project is to use a chemical biology approach to elucidate novel molecular mechanisms involved in the regulation of the Wnt-GSK-3/β-catenin signaling pathway. Towards this end, we carried out a high-throughput image-based cellular screen of 15,000 compounds to discover small molecules that modulate β-catenin levels. Based on our screens, we are investigating novel pathways involved in the stabilization of β-catenin. We have identified a novel mechanism by which HDAC6 inhibitors modulate the acetylation of β-catenin, leading to effects on its localization and in its role in synaptogenesis. Elucidation of the mechanism(s) underlying β-catenin stability will lead to a fundamental understanding of the Wnt signaling pathway and the identification of novel therapeutic targets for neuropsychiatric disorders.


See a list of Dr. Karmacharya's publications


Shaunna S. Berkovitch, PhD, Postdoctoral fellow.
Shaunna received her BS in Chemistry from the Massachusetts Institute of Technology, followed by a a PhD in Molecular and Cellular Biology from Harvard University. For her graduate studies, she investigated novel oligonucleotide inhibition strategies for human telomerase under the mentorship of Professor Gregory Verdine.

Joanne Huang, BS, Research technician.
Joanne received her BS in Biology from the Massachusetts Institute of Technology. As an undergraduate in the laboratory of Prof. Sangeeta Bhatia, she developed a 3-dimensional model of metastatic tumor tissue encapsulated in miniaturized hydrogel scaffolds and also studied the effects of micropatterning on the function and longevity of engineered 3-dimensional liver tissue.

Bradley Watmuff, PhD, Postdoctoral Fellow
Bradley received his PhD in Stem Cell Biology from Monash University, where he worked on the functional development of mouse and human embryonic cell-derived midbrain dopaminergic neurons, under the mentorship of Prof. John Haynes. His current work involves the development of methods for directed differentiation of human induced pluripotent stem cells into hippocampal CA3 neurons.

Laboratory Alumni

Jonathan Iaconelli, BS, Research technician.
Jonathan received his BS in Biology from the Emory University and worked in the laboratory on the underpinnings of HDAC6-mediated changes in acetylation of beta-catenin. He is currently a graduate student in Chemistry at Dartmouth College.

Steven Toffel, Harvard Stem Cell Institute (HSCI) intern
Steven worked on the development of methods to characterize and quantify dendritic spines in cortical neurons differentiated from human iPSCs. He is currently enrolled in an accelerated medical school program at the University of Florida.

Nivanthika Wilamasena, Undergraduate student.
Nivanthika was an undergraduate studnent at Harvard College majoring in Chemical and Physical Biology. She undertook studies aimed at identifying and characterizing novel small molecules that had gene-expression profiles that were anti-correlated to the gene-expression profiles in Parkinson's Disease. She is currently a graduate student at Harvard University.

Berke Sengun, Harvard Stem Cell Institute (HSCI)
intern Berke worked on mechanisms related to HDAC6 effects on beta-catenin in human neural progenitor cells. He is currently a medical student at Koc University in Turkey.

Sun Young Chung, Harvard Stem Cell Institute (HSCI) intern
Sunny worked on the effects of HDAC6 inhibitors on synaptogenesis in human iPSC-derived neurons. She is currently working in the Lorenz Studer laboratory at the Memorial Sloan Kettering Cancer Center.

Elizabeth G. J. O'Brien, AB, Research technician.
Elizabeth received her AB in Molecular and Cellular Biology from Harvard University. Her work involved the gene expression and image-based profiling of human cell to identify disease signatures for psychiatric disorder. She is currently a medical student at Yale University.

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