Paras Mishra

Paras Mishra
Curriculum Vitae

Assistant Professor, Ph.D.
Courtesy appointment in the Department of Anesthesiology
Specialty: MicroRNomics of cardiovascular diseases and diabetic cardiomyopathy
Major Interest: Understanding the mechanism of heart failure in diabetic set up using innovative approaches including miRNA and stem cell with the goal to develop intervention tool to ameliorate cardiomyopathy.

Diabetes is a rapidly increasing menace across the globe that exacerbates morbidity and mortality by increasing the incidence of heart failure. The major interest of our laboratory is to understand the mechanism of structural and functional cardiac remodeling in diabetics with the goal to develop intervention tool. Recently, miRNAs (tiny, conserved, non coding RNAs that modulate gene expression by promoting mRNA degradation or translational repression) have emerged as biomarker and therapeutic target for cardiovascular and other diseases. My research work focuses on finding the candidate miRNAs involved in heart failure especially diabetic cardiomyopathy and using them for ameliorating cardiac dysfunction. Additionally, we are also investigating the role of MMP9, beta2-adrenergic receptors, hydrogen sulfide and homocysteine on miRNA regulation, extracellular matrix remodeling, impaired contractility of cardiomyocytes and heart failure using in vivo, ex-vivo and in vitro approaches. The role of miR-133 as epi-miR and regulation of stem cell survival and differentiation by MMP9 are two new promising areas we are currently pursuing to dissect the mechanism of heart failure at different level.
In the diabetic heart, attenuation of miR-133, β2-AR, Serca2a, decrease in the stem cell number, contractility of cardiomyocytes and fractional shortening; and induction of DNA methylation, MMP9, homocysteine, and autophagy and cardiac fibrosis contributes to diabetic cardiomyopathy as depicted in the figure.

MishraResearchPic

Recent publications:

  1. Chavali V, Tyagi SC, Mishra PK. MicroRNA-133a regulates DNA methylation in diabetic cardiomyocytes. Biochem Biophys Res Commun. 425(3):668-72. 2012. PMID: 22842467.
  2. Mishra PK, Chavali V, Metreveli N, Tyagi SC. Ablation of MMP9 induces survival and differentiation of cardiac stem cell into cardiomyocytes in the diabetic heart; a role of extracellular matrix. Can. J. Physiol. Pharmacol. 90: 353-360. 2012. PMID: 22394373.
  3. Mishra PK, Awe O, Metreveli N, Qipshidze N, Joshua IG, Tyagi SC. Exercise mitigates the homocysteine - beta2-adrenergic receptor interactions to ameliorate contractile dysfunction in diabetes. Int. J. Phys. Pathophy. Phar.3(2):97-106. 2011. PMID: 21760968
  4. Mishra PK, Tyagi N, Sen U, Givvimani S, Tyagi SC. H2S ameliorates oxidative and proteolytic stresses and protects the heart against adverse remodeling in chronic heart failure. Am J Physiol Heart Circ Physiol.298 (2): H451-6. 2010. PMID: 19933416.
  5. Mishra PK, Metreveli N, Tyagi SC. MMP-9 gene ablation and TIMP-4 mitigate PAR-1 mediated cardiomyocyte dysfunction: A plausible role of dicer and miRNA. Cell Biochem. Biophys. 57(2-3):67-76. 2010. PMID: 20422465.

 

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