Ph.D., 1999, College of Basic Science and Humanities
Specialty: Molecular Cardiovascular Physiology
Major Interest: Molecular basis for the regulation of sympathoexcitation.
Research in the laboratory is focused on the neural regulation of cardiovascular function in healthy and disease states. Our central hypothesis is that activated intracellular signaling cascades in the paraventricular nucleus (PVN) of the hypothalamus contribute to the exaggerated sympathoexcitation. We are trying to delineate the underlying molecular mechanism of down-regulation of neuronal nitric oxide synthase(nNOS) contributing to increased sympathoexcitation at transcriptional and post-translational level. We were able to unfold a novel regulatory mechanism of nNOS regulation involving two endogenous nNOS inhibitors: carboxy terminal PDZ ligand of nNOS(CAPON) and protein inhibitor of nNOS(PIN). Silencing of CAPON and PIN leads to increase in nNOS levels with the concurrent decrease in ubiquitin-mediated degradation of nNOS in the PVN. My main focus is to study the coordinated interplay of transcription, phosphorylation and ubiquitination of nNOS and other regulatory proteins in the brain affecting the sympathoexcitation in cardiovascular diseases specifically heart failure, diabetes, and hypertension. The molecules and the signaling pathways involved in this regulation will be important therapeutic targets for the better management of cardiovascular diseases. Overall, my research employs the integrative approach to investigate the neural regulation of cardiovascular function through biochemical and molecular techniques applied to rodent models and neuronal and glial in vitro cell cultures.
- Sharma NM, Nandi SS, Zheng H, Mishra PK, Patel KP. A novel role for miR-133a in centrally mediated activation of the renin-angiotensin system in congestive heart failure. Am J Physiol Heart Circ Physiol. 2017 May 1;312(5):H968-H979. PMID: 28283551
- Sharma NM, Patel KP. Post-translational regulation of neuronal nitric oxide synthase: implications for sympathoexcitatory states. Expert Opin Ther Targets. 2017 Jan;21(1):11-22. Epub 2016 Dec 2. Review. PMID: 27885874
- Sharma NM, Cunningham CJ, Zheng H, Liu X, Patel KP. Hypoxia-Inducible Factor-1α Mediates Increased Sympathoexcitation via Glutamatergic N-Methyl-d-Aspartate Receptors in the Paraventricular Nucleus of Rats With Chronic Heart Failure. Circ Heart Fail. 2016 Nov; 9(11). pii: e003423. PMID: 27810863
- Vaz GC, Sharma NM, Zheng H, Zimmerman MC, Santos RS, Frezard F, Fontes MA, Patel KP. Liposome-entrapped GABA modulates the expression of nNOS in NG108-15 cells. J Neurosci Methods. 2016 Nov 1; 273:55-63. PMID: 27523033
- Nandi SS, Zheng H, Sharma NM, Shahshahan HR, Patel KP, Mishra PK. Lack of miR-133a Decreases Contractility of Diabetic Hearts: A Role for Novel Cross Talk Between Tyrosine Aminotransferase and Tyrosine Hydroxylase. Diabetes. 2016 Oct; 65(10):3075-90. PMID: 27411382