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Faculty Detail    
Name RAJASEKARAN NAMAKKAL SOORAPPAN
  
Campus Address BMR2 533 Zip 2186
Phone  (205) 996-9839
E-mail  rajnsr@uab.edu
Other websites Adjunct Faculty-Division of Cardiovascular Medicine, University of Utah
     

Education
Undergraduate  Bharathidhasan University, Trichy, India    1992  B.Sc. 
Graduate  University of Madras, Chennai, India    1994  M.Sc. 
Graduate  University of Madras, Chennai, India    1996  M.Phil. 
Graduate  University of Madras, Chennai, India    2001  Ph.D. 

Certifications
   
   
   


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Joint Pathology  Molecular & Cellular Pathology Associate Professor
Secondary  Dept of Biomedical Engineering  Dept of Biomedical Engineering Assistant Professor
Center  Comprehensive Cardiovascular Ctr  Comprehensive Cardiovascular Ctr Associate Professor
Center  Comprehensive Diabetes Center  Comprehensive Diabetes Center Associate Professor
Center  Ctr for Exercise Medicine (Org Ret)  Ctr for Exercise Medicine (Org Ret) Associate Professor

Graduate Biomedical Sciences Affiliations
Cellular and Molecular Biology Program 
Medical Scientist Training Program 
Molecular and Cellular Pathology Program 
Pathobiology and Molecular Medicine 

Biographical Sketch 
Dr. Namakkal-Soorappan has spent the last decade and half exploring the regulation of Redox Signaling in heart and skeletal muscle. After completing his undergraduate/master Biology degrees and M.Phil (pre-research dissertation)/ Ph.D Thesis in Biochemistry (1995 – 2001) with Dr. H. Devaraj (Vice-Chair of University Grants Commission, Govt. of India) from the University of Madras in Tamilnadu, Chennai, India, he went on to undertake his post-doctoral training in the Indian Institute of Technology Madras (IITM), Department of Chemistry with Dr. T. S. Chandra (Professor of Biochemistry, IITM) as Department of Biotechnology (Govt. of India) Fellow (2002 – 2003) to investigate the roles of nutraceutical phenolic antioxidants in diabetic humans. He continued his postdoctoral training (2004 – 2008) in the Department of Medicine-Division of Cardiovascular Medicine at the University of Utah, Salt Lake City, UT studying redox regulation of cardiac hypertrophy and heart failure with Dr. Ivor J. Benjamin (Professor of Medicine). He was then promoted as junior faculty (Research Instructor) at the University of Utah in 2008 to pursue his independent research on developing unique reductive stress models utilizing the Beginning-Grant-in-Aid Award from the American Heart Association (AHA-BGI/2008 – 2010). Dr. Namakkal-Soorappan was then promoted as Research Assistant Professor in 2010 and secured funding from National Institute of Aging (NIA-R03 in 2012) to study the “Nrf2 signaling on Cardiac Aging” as well as the National Institute of Health (NHLBI-R01 in 2013) to study the “Reductive Stress on Proteotoxic Cardiac Disease”. In July of 2014, he joined the faculty at The University of Alabama at Birmingham in the Division of Molecular and Cellular Pathology as an Assistant Professor and promoted to Associate Professor in 2019. With these training experiences he has expanded his research through use of transgenic and reductive stress mouse models to identify molecular and genetic mechanisms of pathological cardiac remodeling and heart failure. His outside interests include time with his wife and two young daughters, conducting social awareness rallies on the impact of exercise in cardiac health and writing screen plays for Tamil movies.

Society Memberships
Organization Name Position Held Org Link
American Heart Association (AHA)  Premium Professional Member  http://www.heart.org/HEARTORG/ 
American Physiological Society (APS)  Regular Member  http://www.the-aps.org/ 
Center on Aging, University of Utah, Salt Lake City, Utah (COA)  Life Member  http://aging.utah.edu/ 
International Society for Heart Research (ISHR)  Regular Member  http://www.ishrworld.org/ 
Society For Redox Biology and Medicine, USA (SFRBM)  Faculty Member  http://www.sfrbm.org/ 
Society of Biological Chemistry, India (SBCI)  Life Member   http://www.iisc.ernet.in/sbci/ 
 



Research/Clinical Interest
Title
Nrf2/Keap1 dependent mechanisms for reductive stress in heart and brain
Description
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.

Selected Publications 
Publication PUBMEDID
Shanmugam, G., Crossman, D., Rajasingh, J., Dalley, B., Zhang, J. and Rajasekaran, N.S., 2019. Impaired Regulation of Redox Transcriptome during the Differentiation of iPSCs into Induced Cardiomyocytes (iCMs). bioRxiv, p.519793.   
Jyothidasan, A., Shanmugam, G., Zhang, J., Dally, B., Crossman, D. and Rajasekaran, N.S., 2018. Basal Role for Nrf2-transgne on transcriptional (mRNA/miRNA) regulation in the mouse myocardium. bioRxiv, p.490953.   
Narasimhan, G., Henderson, J., Luong, H.T., Rajasekaran, N.S., Qin, G., Zhang, J. and Krishnamurthy, P., 2019. OBG‐like ATP ase 1 inhibition attenuates angiotensin II‐induced hypertrophic response in human ventricular myocytes via GSK‐3beta/beta‐catenin signalling. Clinical and Experimental Pharmacology and Physiology, 46(8), pp.743-751.   
Sunny, S., Challa, A.K., Barchue, J.P., Ramamurthy, M.T., Crossman, D.K., Pogwizd, S., Cinghu, S. and Namakkal-Soorappan, R., 2020. Transcriptional regulation of structural and functional adaptations in a developing adulthood myocardium. bioRxiv.   
Rajasekaran NS, Devaraj NS, Devaraj H.Vitamin E prevents buthionine sulfoximine-induced biochemical disorders in the rat. J Pharm Pharmacol. 2004 Jan;56(1):91-9.


 		 14983899  
Rajasekaran NS, Devaraj NS, Devaraj H. Modulation of rat erythrocyte antioxidant defense system by buthionine sulfoximine and its reversal by glutathione monoester therapy. Biochim Biophys Acta. 2004 Mar 2;1688(2):121-9.


 		 14990342  
Rajasekaran NS, Nithya M, Rose C, Chandra TS. The effect of finger millet feeding on the early responses during the process of wound healing in diabetic rats. Biochim Biophys Acta. 2004 Aug 4;1689(3):190-201.

 		 15276645 
Yan LJ, Rajasekaran NS, Sathyanarayanan S, Benjamin IJ. Mouse HSF1 disruption perturbs redox state and increases mitochondrial oxidative stress in kidney. Antioxid Redox Signal. 2005 Mar-Apr;7(3-4):465-71.


 		 15706094  
Rajasekaran NS, Sathyanarayanan S, Devaraj NS, Devaraj H. Chronic depletion of glutathione (GSH) and minimal modification of LDL in vivo: its prevention by glutathione mono ester (GME) therapy. Biochim Biophys Acta. 2005 Jun 30;1741(1-2):103-12.
 		 15955453  
Mariappan, N., Soorappan, R.N., Haque, M., Sriramula, S. and Francis, J., 2007. TNF-α-induced mitochondrial oxidative stress and cardiac dysfunction: restoration by superoxide dismutase mimetic Tempol. American Journal of Physiology-Heart and Circulatory Physiology, 293(5), pp.H2726-H2737.  17675574 
Rajasekaran NS, 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. Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Cell. 2007 Aug 10;130(3):427-39.
 		 17693254  
Pinz I, Robbins J, Rajasekaran NS, Benjamin IJ, Ingwall JS. Unmasking different mechanical and energetic roles for the small heat shock proteins CryAB and HSPB2 using genetically modified mouse hearts. FASEB J. 2008 Jan;22(1):84-92.
 		 17846079 
Benjamin IJ, Guo Y, Srinivasan S, Boudina S, Taylor RP, Rajasekaran NS, Gottlieb R, Wawrousek EF, Abel ED, Bolli R. CRYAB and HSPB2 deficiency alters cardiac metabolism and paradoxically confers protection against myocardial ischemia in aging mice. Am J Physiol Heart Circ Physiol. 2007 Nov;293(5):H3201-9.
 		 17873008 
Tannous P, Zhu H, Johnstone JL, Shelton JM, Rajasekaran NS, Benjamin IJ, Nguyen L, Gerard RD, Levine B, Rothermel BA, Hill JA.Autophagy is an adaptive response in desmin-related cardiomyopathy. Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9745-50.
 		 18621691  
Rajasekaran NS, Firpo MA, Milash BA, Weiss RB, Benjamin IJ. Global expression profiling identifies a novel biosignature for protein aggregation R120GCryAB cardiomyopathy in mice. Physiol Genomics. 2008 Oct 8;35(2):165-72.
 		 18628338 
Rajasekaran NS, Devaraj H, Devaraj SN. The effect of glutathione monoester (GME) on glutathione (GSH) depleted rat liver. J Nutr Biochem. 2002 May;13(5):302-306.


 		 2015161  
Zhang H, Rajasekaran NS, Orosz A, Xiao X, Rechsteiner M, Benjamin IJ. Selective degradation of aggregate-prone CryAB mutants by HSPB1 is mediated by ubiquitin-proteasome pathways. J Mol Cell Cardiol. 2010 Dec;49(6):918-30.
 		 20863832  
Rajasekaran NS, Varadharaj S, Khanderao GD, Davidson CJ, Kannan S, Firpo MA, Zweier JL, Benjamin IJ. Sustained activation of nuclear erythroid 2-related factor 2/antioxidant response element signaling promotes reductive stress in the human mutant protein aggregation cardiomyopathy in mice. Antioxid Redox Signal. 2011 Mar 15;14(6):957-71.
 		 21126175 
Muthusamy VR, Kannan S, Sadhaasivam K, Gounder SS, Davidson CJ, Boeheme C, Hoidal JR, Wang L, Rajasekaran NS. Acute exercise stress activates Nrf2/ARE signaling and promotes antioxidant mechanisms in the myocardium. Free Radic Biol Med. 2012 Jan 15;52(2):366-76.
 		 22051043 
Miller CJ, Gounder SS, Kannan S, Goutam K, Muthusamy VR, Firpo MA, Symons JD, Paine R 3rd, Hoidal JR, Rajasekaran NS.Disruption of Nrf2/ARE signaling impairs antioxidant mechanisms and promotes cell degradation pathways in aged skeletal muscle. Biochim Biophys Acta. 2012 Jun;1822(6):1038-50.
 		 22366763 
Brewer AC, Mustafi SB, Murray TV, Rajasekaran NS, Benjamin IJ. Reductive stress linked to small HSPs, G6PD, and Nrf2 pathways in heart disease. Antioxid Redox Signal. 2013 Mar 20;18(9):1114-27.
 		 22938199  
Gounder SS, Kannan S, Devadoss D, Miller CJ, Whitehead KJ, Odelberg SJ, Firpo MA, Paine R 3rd, Hoidal JR, Abel ED, Rajasekaran NS.Impaired transcriptional activity of Nrf2 in age-related myocardial oxidative stress is reversible by moderate exercise training. PLoS One. 2012;7(9):e45697.
 		 23029187 
Kannan S, Muthusamy VR, Whitehead KJ, Wang L, Gomes AV, Litwin SE, Kensler TW, Abel ED, Hoidal JR, Rajasekaran NS.Nrf2 deficiency prevents reductive stress-induced hypertrophic cardiomyopathy. Cardiovasc Res. 2013 Oct 1;100(1):63-73.
 		 23761402 
Xie HB, Cammarato A, Rajasekaran NS, Zhang H, Suggs JA, Lin HC, Bernstein SI, Benjamin IJ, Golic KG.The NADPH metabolic network regulates human αB-crystallin cardiomyopathy and reductive stress in Drosophila melanogaster. PLoS Genet. 2013 Jun;9(6):e1003544.
 		 23818860  
Narasimhan M, Hong J, Atieno N, Muthusamy VR, Davidson CJ, Abu-Rmaileh N, Richardson RS, Gomes AV, Hoidal JR, Rajasekaran NS.Nrf2 deficiency promotes apoptosis and impairs PAX7/MyoD expression in aging skeletal muscle cells. Free Radic Biol Med. 2014 Jun;71:402-14.
 		 24613379  
Haldar M, Kohyama M, So AY, Kc W, Wu X, Briseño CG, Satpathy AT, Kretzer NM, Arase H, Rajasekaran NS, Wang L, Egawa T, Igarashi K, Baltimore D, Murphy TL, Murphy KM.Heme-mediated SPI-C induction promotes monocyte differentiation into iron-recycling macrophages. Cell. 2014 Mar 13;156(6):1223-34.
 		 24630724 
Narasimhan M, Rajasekaran NS.Reductive potential - a savior turns stressor in protein aggregation cardiomyopathy.
Biochim Biophys Acta. 2015 Jan;1852(1):53-60.
 		 25446995 
Verma DR, Khan MF, Tandar A, Rajasekaran NS, Neuharth R, Patel AN, Muhlestein JB, Badger RS.Nickel elution properties of contemporary interatrial shunt closure devices.J Invasive Cardiol. 2015 Feb;27(2):99-104.
 		 25661761 
Dodson M, Redmann M, Rajasekaran NS, Darley-Usmar V, Zhang J.KEAP1-NRF2 signalling and autophagy in protection against oxidative and reductive proteotoxicity.Biochem J. 2015 Aug 1;469(3):347-55.  26205490  
Gomes AV, Rajasekaran NS, Pi X. Redox Signaling and the Cardiovascular and Skeletal Muscle System. Oxid Med Cell Longev. 2015;2015:849095.
 		 26523200 
Narasimhan M, Shelar SB, Shanmugam G, Litovsky SH, Gounder SS, Karan G, Arulvasu C, Kensler TW, Hoidal JR, Darley-Usmar VM, Rajasekaran NS.Disruption of nuclear factor (erythroid-derived-2)-like 2 antioxidant signaling: a mechanism for impaired activation of stem cells and delayed regeneration of skeletal muscle.FASEB J. 2016 Feb 2. pii: fj.201500153. [Epub ahead of print].  26839378  
Swamy, S.M., Rajasekaran, N.S. and Thannickal, V.J., 2016. Nuclear factor–erythroid-2–related factor 2 in aging and lung fibrosis. The American journal of pathology, 186(7), pp.1712-1723.  26839378 
Kumar, R.R., Narasimhan, M., Shanmugam, G., Hong, J., Devarajan, A., Palaniappan, S., Zhang, J., Halade, G.V., Darley-Usmar, V.M., Hoidal, J.R. and Rajasekaran, N.S., 2016. Abrogation of Nrf2 impairs antioxidant signaling and promotes atrial hypertrophy in response to high-intensity exercise stress. Journal of translational medicine, 14(1), pp.1-16.  27048381 
Patibandla, P.K., Rajasekaran, N.S., Shelar, S.B., Giridharan, G.A., Litovsky, S.H. and Sethu, P., 2016. Evaluation of the effect of diminished pulsatility as seen in continuous flow ventricular assist devices on arterial endothelial cell phenotype and function. The Journal of Heart and Lung Transplantation, 35(7), pp.930-932.  27138701 
Wende, A.R., Young, M.E., Chatham, J., Zhang, J., Rajasekaran, N.S. and Darley-Usmar, V.M., 2016. Redox biology and the interface between bioenergetics, autophagy and circadian control of metabolism. Free Radical Biology and Medicine, 100, pp.94-107.  27242268 
Shanmugam G, Narasimhan M, Sakthivel R, Kumar R R, Davidson C, Palaniappan S, Claycomb WC, Hoidal JR, Darley-Usmar VM, Rajasekaran NS. A biphasic effect of TNF-α in regulation of the Keap1/Nrf2 pathway in cardiomyocytes. Redox Biol. 2016 Jun 27; 9:77-89.   27423013  
Ahmed, M.I., Guichard, J.L., Rajasekaran, N.S., Ahmad, S., Mariappan, N., Litovsky, S., Gupta, H., Lloyd, S.G., Denney, T.S., Powell, P.C. and Aban, I., 2016. Disruption of desmin-mitochondrial architecture in patients with regurgitant mitral valves and preserved ventricular function. The Journal of thoracic and cardiovascular surgery, 152(4), pp.1059-1070.  27464577 
Gobinath Shanmugam, Madhusudhanan Narasimhan, Susan Tamowski, Victor Darley-Usmar, and Rajasekaran NS. 2017. Constitutive Activation of Nrf2 Induces a Stable Reductive State in the Mouse Myocardium. Redox Biology, 12;937–945.   28482326 
Gobinath Shanmugam, Madhusudhanan Narasimhan, Robbie L. Conley, Thiagarajan Sairam, Ashutosh Kumar, Ronald P. Mason, Ramalingam Sankaran, John R. Hoidal, and Rajasekaran NS. 2017. Chronic Endurance Exercise Impairs Cardiac Structure and Function in Middle-Aged Mice with Impaired Nrf2 Signaling. Frontiers in Physiology 8 (268).  28515695  
Quiles, J.M., Narasimhan, N., Shanmugam, G., Milash, B., Hoidal, J.R., and Rajasekaran NS. Differential Regulation of miRNA and mRNA Expression in the Myocardium of Nrf2 Knockout Mice. BMC Genomics. 2017 Jul 3;18(1):509.   28673258  
McGinnis GR, Tang Y, Brewer RA, Brahma MK, Stanley HL, Shanmugam G, Rajasekaran NS, Rowe GC, Frank SJ, Wende AR, Abel ED, Taegtmeyer H, Litovsky S, Darley-Usmar V, Zhang J, Chatham JC, Young ME. 2017. Genetic disruption of the cardiomyocyte circadian clock differentially influences insulin-mediated processes in the heart. J Mol Cell Cardiol. 110:80-95.  28736261  
Quiles JM, Narasimhan M, Mosbruger T, Shanmugam G, Crossman D, Rajasekaran NS. 2017. Identification of transcriptome signature for myocardial reductive stress. Redox Biol. 13:568-580.   28768233  
Kain, V., Ingle, K.A., Kachman, M., Baum, H., Shanmugam, G., Rajasekaran, N.S., Young, M.E. and Halade, G.V., 2018. Excess ω-6 fatty acids influx in aging drives metabolic dysregulation, electrocardiographic alterations, and low-grade chronic inflammation. American Journal of Physiology-Heart and Circulatory Physiology, 314(2), pp.H160-H169.  28986357 
Narasimhan, K.K.S., Jayakumar, D., Velusamy, P., Srinivasan, A., Mohan, T., Ravi, D.B., Uthamaraman, S., Sathyamoorthy, Y.K., Rajasekaran, N.S. and Periandavan, K., 2019. Morinda citrifolia and its active principle scopoletin mitigate protein aggregation and neuronal apoptosis through augmenting the DJ-1/Nrf2/ARE signaling pathway. Oxidative medicine and cellular longevity, 2019.  28986357 
Narasimhan, M. and Rajasekaran, N.S., 2017. Cardiac Aging–Benefits of Exercise, Nrf2 Activation and Antioxidant Signaling. In Exercise for Cardiovascular Disease Prevention and Treatment (pp. 231-255). Springer, Singapore.  29022266 
Thiagarajan Sairam, Amit N Patel, Meenu Subrahmanian, Rajendran Gopalan, Steven M Pogwizd, Sudha Ramalingam, Sankaran Ramalingam, Rajasekaran NS (2018). Evidence for hyper-reductive redox in a subset of heart failure patients. Journal of Translational Medicine (In press).  29022266 
Narasimhan, M. and Rajasekaran, N.S., 2016. Exercise, Nrf2 and antioxidant signaling in cardiac aging. Frontiers in physiology, 7, p.241.  29022266 
Bharat D, Cavalcanti RRM, Petersen C, Begaye N, Cutler BR, Costa MMA, Ramos RKLG, Ferreira MR, Li Y, Bharath LP, Toolson E, Sebahar P, Looper RE, Jalili T, Rajasekaran NS, Jia Z, Symons JD, Pon Velayutham AB. 2017. Blueberry Metabolites Attenuate Lipotoxicity-Induced Endothelial Dysfunction. Mol Nutr Food Res. doi: 10.1002/mnfr.201700601.   29024402 
Bolus DJ, Shanmugam G, Narasimhan M, Rajasekaran NS. 2017. Recurrent heat shock impairs the proliferation and differentiation of C2C12 myoblasts. Cell Stress Chaperones. doi: 10.1007/s12192-017-0851-4.   29063376 
Rachel A. Brewer, Helen E. Collins, Ryan D. Berry, Manoja K. Brahma, Brian A. Tirado, Rodrigo A. Peliciari-Garcia, Haley L. Stanley, Adam R. Wende, Heinrich Taegtmeyer, Rajasekaran NS, Victor Darley-Usmar, Jianhua Zhang, Stuart J. Frank, John C. Chatham, Martin E. Young. Temporal partitioning of adaptive responses of the murine heart to fasting. Life Sciences 197 (2018) 30–39.  29410090 
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Keywords
Reductive Stress, Nrf2-Keap1 Signaling, Cardiac Remodeling, Proteotoxicity, Cardiac Aging, Neurodegeneration, Alzheimer's disease