Rajasekaran Namakkal Soorappan

Rajasekaran Namakkal Soorappan, PhD, MPhil, MSci, BSc

Languages spoken: English

Academic Information

Departments Adjunct - Internal Medicine

Divisions: Cardiovascular Medicine

Academic Office Information

raj.soorappan@hsc.utah.edu

Research Interests

  • Nrf2/Keap1 Dependent Mechanisms for Reductive Stress
  • Developing Reductive Stress Models (In Vitro & In Vivo)
  • Nrf2/ARE Signaling and Cytoprotective Mechanisms in the Heart
  • Acute/Chronic Exercise and Nrf2/ARES Signaling in the Myocardium
  • Nrf2-Antioxidant Signaling in Aging Heart and Skeletal Muscle

My laboratory is interested in the transcriptional mechanisms for reductive stress in the heart. Regulation of cytoprotective/antioxidant defense genes is crucial to maintain the redox homeostasis and steady/dynamic function of the myocardium. Nuclear erythroid 2-related factor 2 (Nrf2) is the master transcription factor that regulates numerous (over 100) genes, which code for key antioxidant enzymes. Turning ON or OFF the Nrf2 at will can exert desired effects in the intracellular redox milieu and/or redox signaling to regulate redox sensitive cardio-protective proteins.

Investigating the cause-and-effect relationships between the OXIDATIVE and REDUCTIVE conditions in the myocardium will allow us to understand the critical signals that result in physiological and/or pathological consequences leading to the development of cardiac disease.

To understand these relationships under acute and chronic settings, we have been using in vitro and in vivo models (cardiomyocyte cell cultures, transgenic/knockout mouse models) bearing oxidative or reductive stress. Subsequently, we determine whether or not the SHIFT in REDOX STATE in the context of cardiomyocyte could be a causal mechanism for important cardiac diseases including cardiac hypertrophy, cardiomyopathy, heart failure, myocardial infarction and cardiac arrest. The goal is to define the redox signals in cardiovascular pathophysiology and to develop potential therapeutic measures.

For more detailed information, please go to my lab page, listed at http://medicine.utah.edu/internalmedicine/cardiology/research/

Research Statement

Research Interests:
Nrf2/Keap1 dependent mechanisms for reductive stress
Developing reductive stress models (in vitro & in vivo)
Nrf2/ARE signaling and cytoprotective mechanisms in the heart
Acute/chronic exercise and aging on Nrf2/ARE signaling in the myocardium

Education History

Postdoctoral Fellowship University of Utah
 Postdoctoral Fellow
Indian Institute of Technology Madras
 Postdoctoral Fellow
Doctoral Training University of Madras
 PhD
University of Madras
 MPhil
Graduate Training University of Madras
 MSc
Bharathidasan University
 BSc

Selected Publications

Journal Article

  1. Rajesekaran NS, Saradhadevi Varadharaj, Gayatri D Khanderao, Christopher J Davidson, Sankaranarayanan Kannan, Matthew A Firpo, Jay L Zweier and Ivor J Benjamin (2011). Sustained Activation of Nrf2/ARE Signaling Promotes Reductive Stress in the Human Mutant Protein Aggregation Cardiomyopathy in Mice. Antioxid Redox Signal, 14(6), 957-971.
  2. Sankaranarayanan Kannan, Christopher J Davidson, Vasanthi R Muthusamy, Kamalanathan Sadhaasivam, Russell Richardson, Aldrin V Gomes, John R Hoidal and Rajesekaran NS (2013). Nrf2 Deficiency Promotes Apoptosis and Impairs Pax7/MyoD Lineage in Aging Skeletal Muscle. FASEB J, (Revising).
  3. Sankaranarayanan Kannan, Vasanthi R Muthusamy, Kevin J Whitehead, Aldrin V Gomes, Li Wang, Sheldon E Litwin, Thomas W Kensler, E Dale abel, John R Hoidal, Rajesekaran NS (2013). Nrf2 Deficiency Prevents Reductive Stress Induced Hypertrophic Cardiomyopathy. Cardiovasc Res, (Epub), PMID:23761402.
  4. Heng B Xie, Anthony Cammarato, Rajasekaran NS, Huali Zhang, Jennifer A Suggs, Ho-Chen Lin, Sanford I Bernstein, Ivor Benjamin and Kent G Golic (2013). The NADPH metabolic network regulates human aB-crystallin cardiomyopathy and reductive stress in Drosophila melanogaster. PLoS Genet, 9(6), e1003544.
  5. Gounder SS, Kannan S, Devadoss D, Miller CJ, Whitehead KS, Odelberg SJ, Firpo MA, Paine R 3rd, Hoidal JR, Abel ED, Namakkal Soorappan, Rajasekaran (9/24/12). Impaired transcriptional activity of nrf2 in age-related myocardial oxidative stress is reversible by moderate exercise training. PLoS One, 7(9), e45697.
  6. Brewer A, Banerjee Mustafi S, Murray TV, Namakkal Soorappan, Rajasekaran, Benjamin I (9/3/12). Reductive Stress Linked to Smaal HSPs, G6PD and Nrf2 Pathways in Heart Disease. Antioxid Redox Signal.
  7. Miller CJ, Gounder SS, Kannan S, Goutam K, Muthusamy VR, Firpo MA, Symons JD, Paine R 3rd, Hoidal JR, Namakkal Soorappan, Rajasekaran (6/2012). Disruption of Nrf2/ARE signaling impairs antioxidant mechanisms and promotes cell degradation pathways in aged skeletal muscle. Biochim Biophys Acta, 1822(6), 1038-1050.
  8. Muthusamy VR, Kannan S, Sadhaasivam K, Gounder SS, Davidson CJ, Boeheme C, Hoidal JR, Wang L, Namakkal Soorappan, Rajasekaran (01/15/12). Acute exercise stress activates Nrf2/ARE signaling and promotes antioxidant mechanisms in the myocardium. Free Radic Biol Med, 52(2), 366-376.
  9. Zhang H, Namakkal Soorappan, Rajasekaran, Orosz A, Xiao X, Rechsteiner M, Benjamin IJ (12/2010). Selective degradation of aggregate-prone CryAB mutants by HSPB1 is mediated by ubiquitin-proteasome pathways. J Mol Cell Cardiol, 49(6), 918-30.
  10. Pinz I, Robbins J, Namakkal Soorappan, Rajasekaran, Benjamin IJ, Ingwall JS (2008). Unmasking different mechanical and energetic roles for the small heat shock proteins CryAB and HSPB2 using genetically modified mouse hearts. FASEB J, 22(1), 84-92.
  11. Tannous P, Zhu H, Johnstone JL, Shelton JM, Namakkal Soorappan, Rajasekaran, Benjamin IJ, Nguyen L, Gerard RD, Levine B, Rothermel BA, Hill JA (2008). Autophagy is an adaptive response in desmin-related cardiomyopathy. Proc Natl Acad Sci U S A, 105(28), 9745-50.
  12. Rajesekaran NS, Firpo MA, Milash BA, Weiss RB, Benjamin IJ (2008). Global expression profiling identifies a novel biosignature for protein aggregation R120GCryAB cardiomyopathy in mice. Physiol Genomics, 35(2), 165-72.
  13. Benjamin IJ, Guo Y, Srinivasan S, Boudina S, Taylor RP, Namakkal Soorappan, Rajasekaran, Gottlieb R, Wawrousek EF, Abel ED, Bolli R (2007). CRYAB and HSPB2 deficiency alters cardiac metabolism and paradoxically confers protection against myocardial ischemia in aging mice. Am J Physiol Heart Circ Physiol, 293(5), H3201-9.
  14. Mariappan N, Namakkal Soorappan, Rajasekaran, Haque M, Sriramula S, Francis J (2007). TNF-alpha-induced mitochondrial oxidative stress and cardiac dysfunction: restoration by superoxide dismutase mimetic Tempol. Am J Physiol Heart Circ Physiol, 293(5), H2726-37.
  15. Namakkal Soorappan, Rajasekaran, Connell P, Christians ES, Yan LJ, Taylor RP, Orosz A, Zhang XQ, Stevenson TJ, Peshock RM, Leopold JA, Barry WH, Loscalzo J, Odelberg SJ, Benjamin IJ (2007). Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Cell, 130(3), 427-39.
  16. Namakkal Soorappan, Rajasekaran, Sathyanarayanan S, Devaraj NS, Devaraj H (2005). Chronic depletion of glutathione (GSH) and minimal modification of LDL in vivo: its prevention by glutathione mono ester (GME) therapy. Biochim Biophys Acta, 1741(1-2), 103-12.
  17. Yan LJ, Namakkal Soorappan, Rajasekaran, Sathyanarayanan S, Benjamin IJ (2005). Mouse HSF1 disruption perturbs redox state and increases mitochondrial oxidative stress in kidney. Antioxid Redox Signal, 7(3-4), 465-71.
  18. Hegde PS, Namakkal Soorappan, Rajasekaran, Chandra TS (2005). Effects of the antioxidant properties of millet species on oxidative stress and glycemic status in alloxan-induced rats. Nutr Res, 25(12), 1109-1120.
  19. Namakkal Soorappan, Rajasekaran, Nithya M, Rose C, Chandra TS (2004). The effect of finger millet feeding on the early responses during the process of wound healing in diabetic rats. Biochim Biophys Acta, 1689(3), 190-201.
  20. Namakkal Soorappan, Rajasekaran, Devaraj NS, Devaraj H (2004). Modulation of rat erythrocyte antioxidant defense system by buthionine sulfoximine and its reversal by glutathione monoester therapy. Biochim Biophys Acta, 1688(2), 121-9.
  21. Namakkal Soorappan, Rajasekaran, Devaraj NS, Devaraj H (2004). Vitamin E prevents buthionine sulfoximine-induced biochemical disorders in the rat. J Pharm Pharmacol, 56(1), 91-9.
  22. Namakkal Soorappan, Rajasekaran, Devaraj H, Devaraj SN (2002). The effect of glutathione monoester (GME) on glutathione (GSH) depleted rat liver. J Nutr Biochem, 13(5), 302-306.