- Research Professor of Psychiatry, Anatomy and Cell Biology, and Neuroscience
- Director of the Psychosis Program
- rsharma [at] uic.edu
- (312) 413-4508
Dr. Rajiv P. Sharma is a Research Professor of Psychiatry. Over the past 30 years, he has examined multiple aspects of the schizophrenia illness, including clinical presentations, biochemical studies (hormones, immune molecules, monoamine metabolites, neuropeptides), as well as molecular studies in living subjects, postmortem brain samples, and cell studies. His research is funded by NIH. He is currently focusing on the dissection of epigenetic gene regulation in schizophrenia, pertaining to immune function, cognition, treatment response.
Dr Rajiv Sharma completed his medical school at Osmania University in the historic south- central Indian city of Hyderabad. He completed his Psychiatric Residency at the Mount Sinai Medical Center in New York City. During his residency, he was extensively trained in psychoanalytic theory/practice as well as phenomenology. He has trained in population/psychiatric genetics at the NIMH. In addition, he is formally trained in applied mathematics.
His career is focused on the major psychotic disorders including schizophrenia and bipolar disorder. During the first phase of his scientific investigations he published a stream of neurochemical findings in psychiatric patients. These include the characterization of catecholamine metabolites (HVA, 5HIAA, MHPG, phenylacetic acid), neurohormones (cortisol, Growth hormone, prolactin), and neuropeptides (neurotensin, somatostatin, TRH). He also conducted the first study of 1H NMR (proton spectroscopy) in the human brain, and formulated the role or presynaptic 5Ht1A sertonergic receptors in the expression of the negative symptoms of schizophrenia, especially as a mechanism for the unique effects of clozapine. With regards to therapeutic interventions, he has directly tested the GABA schizophrenia hypothesis with the GABA transport inhibitor tiagabine.
The second phase of his career started with a total retooling in the cellular experimental laboratory. Under the mentorship of the late Dr Erminio Costa and in the laboratory of Dr Dennis Grayson, and funded by a KO1 NIMH training grant, he established new methods to study epigenetic mechanisms in psychiatric disease. These include the earliest reports describing a resistant type of chromatin in both the peripheral blood and postmortem brain samples of patients with schizophrenia. His lab is funded by the NIH to study restrictive chromatin formation, to measure it’s responsivity to pharmacological intervention, and to characterize its distribution across the genome in postmortem brain tissue. He is exploring the role of epigenetics in quasi-embryological routines such as the formation of adipose tissue in schizophrenia, and extending these theoretical considerations into the area of regenerative neurobiology.
Dr. Sharma has received numerous awards for his scientific activities, as well as teaching awards at the university level. He has been multiply funded by the NIMH. He has received investigator initiated grants, and also conducted clinical trials for the pharmaceutical industry. He has authored/coauthored over a 100 peer reviewed publications. He is an adhoc reviewer for the NIH, for the French National Research agency, and is a reviewer on more than 30 neuroscience and psychiatric journals. He has a long list of trainees, medical students, residents, junior faculty, graduate students and postdocs to whose research careers he has contributed.
Epigenetic mechanisms of psychotic disorders and regenerative neurobiology.
Dr. Sharma’s research laboratory is investigating gene regulation in neurons and cells, with a special focus on translational research (clinical samples, postmortem brain)
Chen Y, Sharma RP, Costa RH, Costa E, Grayson DR. On the epigenetic regulation of human reelin promoter expression. Nucleic Acids Res. 2002;30(13):2930-2939.
Tremolizzo L, Carboni G, Ruzicka WB, Mitchell CP, Sugaya I, Tueting P, Sharma RP, Grayson DR, Costa E, Guidotti A. An epigenetic mouse model for molecular and behavioral neuropathologies related to schizophrenia vulnerability. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):17095-100.
Sharma RP. Schizophrenia, Epigenetics and Ligand activated nuclear transcription factors: A framework for chromatin therapeutics. Schiz Res 2005, Jan 1; 72 (2-3): 79-90.
Noh JS, Sharma RP, Veldic M, Salvacion AA, Jia X, Chen Y, Costa E, Guidotti A, Grayson DR. DNA methyltransferase 1 regulates reelin mRNA expression in mouse primary cortical cultures. Proc Natl Acad Sci U S A. 2005 Jan 25;.
Grayson DR., Jia, X., Chen, Y., Sharma RP., Mitchell CP., Guidotti A, Costa E. Promoter Hypermethylation in Schizophrenia, (Proc Natl Acad Sci U S A, Jun 28;102(26): 9341-6 2005).
Sharma RP, Rosen CR, Kartan S, Guidotti A, Costa E, Grayson D, Chase K. Valproic acid and chromatin remodeling in schizophrenia and bipolar disorder: preliminary results from a clinical population. Schizophrenia Research Dec;88(1-3):227-31 2006
Grayson DR, Chen Y, Costa E, Dong E, Guidotti A, Kundakovic M, Sharma RP. The human reelin gene: transcription factors (+),repressors (-) and the methylation switch (+/-) in schizophrenia. Pharmacol Ther. 2006 Jul;111(1):272-86. Epub 2006 Mar 30.
Sharma RP, Grayson DR, Gavin D. Histone deactylase 1 expression is increased in the prefrontal cortex of schizophrenia subjects: Analysis of the National Brain Databank microarray collection, Schizophr. Res. (2007), doi:10.1016/j.schres.2007.09.020
Sharma RP, Grayson DR, Gavin D. Histone deactylase 1 expression is increased in the prefrontal cortex of schizophrenia subjects: analysis of the National Brain Databank microarray collection. Schizophr Res. 2008a Jan;98(1-3):111-7
Sharma RP, Tun N, Grayson DR. Depolarization induces downregulation of DNMT1 and DNMT3a in primary cortical cultures. Epigenetics. 2008 Mar-Apr;3(2):74-80. Epub 2008 Mar 12. PMID: 18536530 [PubMed - indexed for MEDLINE
Gavin D, Kartan S, Chase K, Grayson DR, Sharma RP. Reduced baseline acetylated histone 3 levels, and a 3 blunted response to HDAC inhibition in lymphocytes 4 cultures from schizophrenia subjects, Schizophr Res. 2008 Aug;103(1-3):330-2. Epub 2008 Jun 9.. PMID: 18539439 [PubMed - indexed for MEDLINE]
Gavin DP, Rosen C, Chase K, Grayson DR, Tun N, Sharma RP. Dimethylated lysine 9 of histone 3 is elevated in schizophrenia and exhibits a divergent response to histone deacetylase inhibitors in lymphocyte cultures. J Psychiatry Neurosci. 2009 May;34(3):232-7. PubMed PMID: 19448855
Gavin DP, Sharma RP. Histone modifications, DNA methylation, and schizophrenia. Neurosci Biobehav Rev. 2010 May;34(6):882-8. Epub 2009 Oct 30. PubMed PMID: 19879893;
Sharma RP, Gavin DP, Grayson DR. CpG Methylation in Neurons: Message, Memory, or Mask? Neuropsychopharmacology. 2010 Jul 14. [Epub ahead of print] PubMed PMID: 20631690.
Gavin DP, Sharma RP, Chase K, Martriasciano F, Dong E, Guidotti S. et al.Growth arrest and DNA-damage-inducible, beta (GADD45b)-mediated DNA Demethylation in Major Psychosis (in press, Neuropsychopharmacology Aug 2011).
Sharma RP, Chase KA. Increasing neuronal 'stemness': Chromatin relaxation and the expression of reprogramming genes in post-mitotic neurons. Med Hypotheses. 2012 Apr;78(4):553-4. Epub 2012 Feb 10. PubMed PMID: 22326495.
Sharma RP, Gavin DP, Chase KA. Heterochromatin as an incubator for pathology and treatment non-response: implication for neuropsychiatric illness. Pharmacogenomics J. 2012 Oct;12(5):361-7. doi: 10.1038/tpj.2011.64. Epub 2012 Jan 17. PubMed PMID: 22249356PubMed PMID: 22249356.
Chase KC, Sharma RP. Nicotine induces chromatin remodelling through decreases in the methyltransferases GLP, G9a, Setdb1 and levels of H3K9me2. Int J Neuropsychopharmacol. 2012 Oct 16:1-10. [Epub ahead of print] PubMed PMID: 23067581)
Sharma RP. Blood chromatin as a biosensor of the epigenetic milieu: a tool for studies in living psychiatric patients. (in press Epigenomics. Aug 2012).
|The H3K9 Histone Switch; 'Levels' In Schizophrenia Blood And Brain||Schizohrenia can impact almost all domains of mental functioning, such as perception, affect, memory and cognition, and social disability.||
||Psychosis Research Program||On-going|