Rahul Bharadwaj, PhD Biomedical Sci. - University of Massachusetts Medical School, Brudnick Neuropsychiatric Research Institute, 2013. Johns Hopkins School of Medicine Neuropathology Fellow, 2015.
Research Summary The causal mechanisms of neuropsychiatric disorders include a combination of genetic and epigenetic mechanisms that alter the molecular make-up of the brain. While a detailed understanding of chromatin structure and epigenetics holds the key to understanding the basis of altered transcription regulation in psychiatric disorders, understanding neuroanatomy and pathology are critical to consider in order to begin to understand the basis of brain disorders. I have therefore gained expertise in the molecular, anatomical and pathological basis for psychiatry in postmortem human brain models over my graduate and postdoctoral research. Examples of multi-modal approaches I have applied combining genetics, epigenetics and neurophysiology include my research published in Neuron, 84(5):997-1008, The Journal of Neuroscience 33(29):11839-51 and the Journal of Neuroscience Research Oct 24,2016. One of my most interesting findings of relevance to schizophrenia, working memory physiology and gene expression regulation in postmortem human brain is the sequence-specified conserved chromatin loop structure (350 Kilobase span) at the NMDA2B receptor locus in human brain prefrontal cortex. Sequences involved in the formation of this chromatin loop structure harbor regulatory elements and genetic risk variants for schizophrenia and working memory function. Of greater mechanistic relevance, these sequences show activity dependent chromatin changes and correlate with NMDAR2B expression in mature neuron cultures. I currently employ my epigenetics expertise in post-traumatic stress disorder (PTSD) research. My research aims to understand how different epigenetic signals (DNA methylation, histone modifications and higher order chromatin structures) in postmortem brain tissue combine with genetic risk to alter the neuronal circuitry in PTSD.