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
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 M.D. and Ph.D. 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 Prof. Steven D. Schwartz.
He did an Internship in Internal Medicine at MGH, followed by a Residency in Psychiatry in the MGH-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.
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. These iPSCs are then differentiated along the neuronal lineage. We intend to profile these 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 preliminary results, we are investigating novel pathways involved in the stabilization of β-catenin. 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 bipolar disorder.
Shaunna S. Berkovitch, Ph.D., Postdoctoral fellow.
Shaunna received her B.S. in Chemistry from the Massachusetts Institute of Technology, followed by a a Ph.D. 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 Prof. Gregory Verdine.
Jonathan Iaconelli, B.S., Research technician.
Jonathan received his B.S. in Biology from the Emory University. As an undergraduate student, he worked on the biological activity of farnesyl transferase inhibitors in the laboratory of Prof. Adam Marcus. He has also worked on the synthesis and characterization of pyrrole derivatives and on characterization of small-molecule inhibitors of cell cycle proteins.
Elizabeth G. J. O'Brien , A.B., Research technician.
Elizabeth received her A.B. in Molecular and Cellular Biology from Harvard University. For her undergraduate thesis, she worked on identification of genes involved in cell wall intergrity and virulence in Cryptococcus neoformans under the mentorship of Prof. Eleftherios Mylonakis.
Joanne Huang, B.S., Research technician.
Joanne received her B.S. 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.
Nivanthika Wilamasena, Undergraduate student.
Nivanthika is a junior at Harvard College majoring in Chemical and Physical Biology. Before joining our group, she worked in the Laboratory for Experimental Alzheimer Drugs at Brigham and Women's Hospital, where she synthesized small molecules to develop clinical candidates for screening. She has also undertaken studies on the effects of pseudoephedrine in neuronal cells.
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