Rakesh Karmacharya, MD, PhD :: The Baker Center For Children and Families

Rakesh Karmacharya, MD, PhD

Associate Professor

Research Roles/Affiliations

Principal Investigator, Center of Genomic Medicine, Massachusetts Geneneral Hospital

Medical Director, OnTrack Program for First-Episode Psychosis, McLean Hospital

Faculty, Harvard Chemical Biology and Neuroscience Graduate Program

Associate Member, Chemical Biology & Therapeutic Science Program. Board Institute

Faculty Affiliate, Harvard Stem Cell Institute

Contact Information

MGH Center for Genomic Medicine, 185 Cambridge Street, CPZN6, Boston, MA 02114

Phone: (617) 726-5119

E-mail: karmacharya@mgh.harvard.edu

Relevant Links

PiN Profile

CGM Profile

NCBI Bibliography

Harvard Catalyst Profile

Research

Our research focuses on interrogating the cellular and molecular underpinnings of schizophrenia, bipolar disorder and autism spectrum disorders through investigations at the intersection of chemical biology and stem cell biology. We generate induced pluripotent stem cells from patients in the clinic and generate brain cell types hypothesized to be involved in these disorders, including cortical pyramidal neurons, inhibitory interneurons, astrocytes, microglia and brain microvascular endothelial cells. In addition, we generate brain organoids from the patient-derived stem cells to study aspects of neural connectivity, function and cell-cell interactions in a three-dimensional context. We utilize integrative approaches including transcriptomics, proteomics, mitochondrial bioenergetics and functional studies of neural activity using multi-electrode arrays. We are also studying gene-environment interactions in these disorders by investigating how neurodevelopment in brain organoids is affected in the setting of perturbations with environmental factors, with a current focus on pro-inflammatory cytokines implicated in maternal immune activation. Lastly, we are interested in delineating molecular mechanisms underlying synaptic function as they relate to cognitive dysfunction in neuropsychiatric disorders, an studying the Arc protein in human neurons in this context. We are working on generating new small molecule leads for therapeutic development that can improve cognitive deficits in these disorders through modulation of Arc activity.