Neeru Sharma

Neeru Sharma
Curriculum Vitae

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 normal 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 nNOS contributing to increased sympathoexcitation at transcriptional and post-translational level. We were able to unfold a novel regulatory mechanism involving two endogenous nNOS inhibitors: CAPON and PIN. Silencing of CAPON and PIN leads to increase in nNOS levels with concurrent decrease in ubiquitin-mediated degradation of nNOS. My main focus is to study the coordinated interplay of transcription, phosphorylation and ubiquitination on nNOS and other regulatory proteins in the PVN affecting the sympathoexcitation. The molecules and the signaling pathways involved in this regulation will be important therapeutic targets for 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 Hypothesis

  1. Neeru M. Sharma, Hong Zheng, Yi-Fan Li and Kaushik P. Patel. Nitric oxide Inhibits the expression of AT1 receptors in neurons. Am JPhysiol Cell Physiol., 2012; 302(8): C1162-73.  PMID: 22218225
  2. Laura H. R. Leite, Neeru M Sharma,  Sangeeta Bafna, Hong Zheng, Cândido C. Coimbra, & Kaushik P. Patel. Construction and Validation of Lentiviral Vector Carrying Rat Neuronal Nitric Oxide Synthase In Vitro and In Vivo. J Neurosci Method. 2012; 211(1): 77-83.  PMID: 22921486
  3. Hong Zheng, Neeru M. Sharma, Xuefei Liu and Kaushik P. Patel. Exercise training normalizes enhanced sympathetic activation from the paraventricular nucleus in chronic heart failure: role of angiotensin II.  Am J Physiol Regul Integr Comp Physiol., 2012; 303(4): R387-94.  PMID: 2218804
  4. Neeru M. Sharma, Hong Zheng, Parmender P Mehta Yi-Fan Li and Kaushik P. Patel. Decreased nNOS in the PVN leads to increased sympathoexcitation in chronic heart failure: role for CAPON and Ang II. Cardiovascular Res., 2011; 92(2): 348-57  PMID: 21831995
  5. Neeru M Sharma, Olga V Kochenova and Polina V Shcherbakova. The non-canonical protein binding site at the monomer-monomer interface of yeast PCNA regulates the Rev1-PCNA interaction and Polζ/Rev1-dependent translesion DNA synthesis. J Biol Chem., 2011; 286(38): 33557-33566.  PMID: 21799021