Sathnur Pushpakumar, M.D., Ph.D.

Sathnur Pushpakumar, M.D., Ph.D.

Sathnur B. Pushpakumar, M.D., Ph.D.
Assistant Professor (Term)
sbpush01@louisville.edu

 

The overall focus of our laboratory is to better understand renovascular and cardiovascular remodeling in hypertension, hyperhomocysteinemia (HHcy) and diabetes. We are investigating the role of epigenetic modifications, macrophage polarization and matrix metalloproteinases and their inhibitors, tissue inhibitors of metalloproteinases in causing microvascular pathology. The disruption of microvascular integrity is an initiating or intermediate promoting event in a chain of events leading to cardiac and renal failure. Therefore, regeneration of the microenvironment is a key component for regeneration in cardiac and renal failure. Our lab is oriented toward investigating the mechanisms of microvascular derangements and its mitigation in various disease scenarios.

HHcy causes tissue damage by a variety of mechanisms including oxidant-antioxidant imbalance, inflammation, apoptosis, and cellular proliferation. Recent studies have revealed that epigenetic factors may regulate some of these mechanisms contributing to renal injury. Our lab has recently shown that abnormal DNA methylation during HHcy is associated with renovascular and aortic damage. Our research is currently focused on using epigenetic inhibitor to reduce inflammation and modify extracellular matrix metabolism in HHcy mediated renal and vascular injury.

 

Selected Peer-reviewed Publications

 

  1. Pushpakumar S, Kundu S, Narayanan N, Sen U. DNA hypermethylation in hyperhomocysteinemia contributes to abnormal extracellular matrix metabolism in the kidney. FASEB J. 2015 Jul 29. pii: fj.15-272443. [Epub ahead of print]
  2. Givvimani S, Kundu S, Pushpakumar S, Doyle V, Narayanan N, Winchester LJ, Veeranki S, Metreveli N, Tyagi SC. Hyperhomocysteinemia: a missing link to dysfunctional HDL via paraoxanase-1. Can J Physiol Pharmacol. 2015 Apr 15:1-9. [Epub ahead of print]
  3. Givvimani S, Pushpakumar S, Metreveli N, Veeranki S, Kundu S, Tyagi SC. Role of mitochondrial fission and fusion in cardiomyocyte contractility. Int J Cardiol. 2015 May 6;187:325-33. doi: 10.1016/j.ijcard.2015.03.352. Epub 2015 Mar 25.
  4. Kundu S, Pushpakumar S, Sen U. MMP-9 and NMDA receptor-mediated mechanism of diabetic renovascular remodeling and kidney dysfunction: Hydrogen sulfide is a key modulator. Nitric Oxide. 2015 Apr 30;46:172-85. doi: 10.1016/j.niox.2015.02.003. Epub 2015 Feb 7.
  5. Kundu S, Pushpakumar S, Khundmiri SJ, Sen U. Hydrogen sulphide mitigates hyperglycemic remodelling via liver kinase B1-adenosine monophosphate-activated protein kinase signalling. Biochim Biophys Acta. 2014 Dec;1843(12):2816-26. doi: 10.1016/j.bbamcr.2014.08.005. Epub 2014 Aug 13
  6. Pushpakumar SB, Kundu S, Utpal Sen. Endothelial dysfunction: The link between homocysteine and hydrogen sulfide. Curr Med Chem. 2014;21(32):3662-72.
  7. Utpal S, Pushpakumar SB, Amin MA, Tyagi SC. Homocysteine in renovascular complications: Hydrogen sulfide is a modulator and plausible anaerobic ATP generator. Nitric Oxide. 2014 Sep 15;41:27-37. doi: 10.1016/j.niox.2014.06.006. Epub 2014 Jun 22.
  8. Givvimani S, Pushpakumar S, Veeranki S, Tyagi SC. Dysregulation of Mfn2 and Drp-1 proteins in heart failure. Can J Physiol Pharmacol. 2014 Jul;92(7):583-91. doi: 10.1139/cjpp-2014-0060. Epub 2014 May 9