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 seeks to understand the neural regulation of cardiovascular function in health and disease states. The broad research interest is to study the coordinated interplay of transcription, posttranscriptional and post-translational mechanisms, neurons and astrocytes relationship and crosstalk in the central nervous system affecting the sympathoexcitation during cardiovascular diseases. Studies in the laboratory are also directed towards uncovering how these pathways are deregulated in disease conditions such as hypertension, heart failure, and diabetes. The molecules and the signaling pathways involved in this regulation will be important therapeutic targets for the better management of cardiovascular diseases. Our central hypothesis is that cardiovascular pathologies initiate a signaling cascades leading to the downregulation of neuronal nitric oxide synthase (nNOS), and a concurrent increase in NMDA (N-Methyl-D-aspartic acid) receptor 1 in the paraventricular nucleus (PVN) of the hypothalamus contributing to the exaggerated sympathoexcitation. We were able to unfold a novel post-translational regulatory mechanism of nNOS 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. Overall, our research employs the integrative approach to investigate the neural regulation of cardiovascular function through biochemical and molecular techniques applied to rodent models, state-of-the-art genetic models and neuronal and glial in vitro 3D co-culture system.
- 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