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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
Henderson J, Dubey PK, Patil M, Singh S, Dubey S, Namakkal Soorappan R, et al. microRNA-377 Signaling Modulates Anticancer Drug-Induced Cardiotoxicity in Mice. Frontiers in Cardiovascular Medicine. 2021;8.  34485421 
Quiles JM, Pepin ME, Sunny S, Shelar SB, Challa AK, Dalley B, Hoidal JR, Pogwizd SM, Wende AR, Rajasekaran NS. Identification of Nrf2-responsive microRNA networks as putative mediators of myocardial reductive stress. Sci Rep. 2021 Jun 7;11(1):11977. doi: 10.1038/s41598-021-90583-y. PMID: 34099738; PMCID: PMC8184797.  34099738 
Byrne NJ, Rajasekaran NS, Abel ED, Bugger H. Therapeutic potential of targeting oxidative stress in diabetic cardiomyopathy. Free Radic Biol Med. 2021 Jun;169:317-342. doi: 10.1016/j.freeradbiomed.2021.03.046. Epub 2021 Apr 25. PMID: 33910093; PMCID: PMC8285002.  33910093 
Ravichandran G, Lakshmanan DK, Murugesan S, Elangovan A, Rajasekaran NS, Thilagar S. Attenuation of protein glycation by functional polyphenolics of dragon fruit (Hylocereus polyrhizus); an in vitro and in silico evaluation. Food Res Int. 2021 Feb;140:110081. doi: 10.1016/j.foodres.2020.110081. Epub 2020 Dec 29. PMID: 33648300.  33648300 
Sunny S, Challa AK, Qiao A, Jyothidasan A, Krishnamurthy P, Ramamurthy MT, Crossman DK, Pogwizd S, Cinghu S, Rajasekaran NS. Transcriptional Regulation of Structural and Functional Adaptations in a Developing Adulthood Myocardium. Cardiol Cardiovasc Med. 2021;5(5):454-470. doi: 10.26502/fccm.92920215. Epub 2021 Sep 7. PMID: 34497977; PMCID: PMC8423094.  34497977 
Klionsky DJ,...,Rajasekaran NS,...,Tong CK. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1. Autophagy. 2021 Jan;17(1):1-382. doi: 10.1080/15548627.2020.1797280. Epub 2021 Feb 8. PMID: 33634751; PMCID: PMC7996087.  33634751 
Kain V, Ingle KA, Rajasekaran NS, Halade GV. Activation of EP4 receptor limits transition of acute to chronic heart failure in lipoxygenase deficient mice. Theranostics. 2021 Jan 1;11(6):2742-2754. doi: 10.7150/thno.51183. PMID: 33456570; PMCID: PMC7806484.  33456570 
Murugesan S, Saravanakumar L, Powell MF, Rajasekaran NS, Kannappan R, Berkowitz DE. Role of exosomal microRNA signatures: An emerging factor in preeclampsia-mediated cardiovascular disease. Placenta. 2021 Jan 1;103:226-231. doi: 10.1016/j.placenta.2020.10.033. Epub 2020 Oct 28. PMID: 33171429; PMCID: PMC8278543.  33171429 
Shanmugam, G., Wang, D., Gounder, S.S., Fernandes, J., Litovsky, S.H., Whitehead, K., Radhakrishnan, R.K., Franklin, S., Hoidal, J.R., Kensler, T.W. and Dell'Italia, L., 2020. Reductive stress causes pathological cardiac remodeling and diastolic dysfunction. Antioxidants & redox signaling, 32(18), pp.1293-1312.  32064894 
Rajasekaran, N.S., 2020. Reductive Stress: Neglected Science. Antioxidants & redox signaling.  32375496 
Rajasekaran, N.S., Shelar, S.B., Jones, D.P. and Hoidal, J.R., 2020. Reductive stress impairs myogenic differentiation. Redox biology, 34, p.101492.  32361680 
Narasimhan, K.K.S., Devarajan, A., Karan, G., Sundaram, S., Wang, Q., van Groen, T., Del Monte, F. and Rajasekaran, N.S., 2020. Reductive stress promotes protein aggregation and impairs neurogenesis. Redox biology, 37, p.101739.  33242767 
Pecha, P.P., Almishaal, A.A., Mathur, P.D., Hillas, E., Johnson, T., Price, M.S., Haller, T., Yang, J., Rajasekaran, N.S., Firpo, M.A. and Park, A.H., 2020. Role of Free Radical Formation in Murine Cytomegalovirus–Induced Hearing Loss. Otolaryngology–Head and Neck Surgery, 162(5), pp.709-717.  32041493 
Kim, S., Song, J., Ernst, P., Latimer, M.N., Ha, C.M., Goh, K.Y., Ma, W., Rajasekaran, N.S., Zhang, J., Liu, X. and Prabhu, S.D., 2020. MitoQ regulates redox-related noncoding RNAs to preserve mitochondrial network integrity in pressure-overload heart failure. American Journal of Physiology-Heart and Circulatory Physiology, 318(3), pp.H682-H695.  32004065 
Miller, J.M., Mardhekar, N.M., Pretorius, D., Krishnamurthy, P., Rajasekaran, N.S., Zhang, J. and Kannappan, R., 2020. DNA damage-free iPS cells exhibit potential to yield competent cardiomyocytes. American Journal of Physiology-Heart and Circulatory Physiology, 318(4), pp.H801-H815.  32057252 
Murugesan, S., Saravanakumar, L., Powell, M.F., Kannappan, R. and Berkowitz, D.E., 2020. Role of exosomal microRNA signatures: An emerging factor in preeclampsia-mediated cardiovascular disease. Placenta.  33171429 
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.   
Haglund, T.A., Rajasekaran, N.S., Smood, B., Giridharan, G.A., Hoopes, C.W., Holman, W.L., Mauchley, D.C., Prabhu, S.D., Pamboukian, S.V., Tallaj, J.A. and Rajapreyar, I.N., 2019. Evaluation of flow-modulation approaches in ventricular assist devices using an in-vitro endothelial cell culture model. The Journal of Heart and Lung Transplantation, 38(4), pp.456-465.  30503074 
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.   
Devarajan, A., Rajasekaran, N.S., Valburg, C., Ganapathy, E., Bindra, S. and Freije, W.A., 2019. Maternal perinatal calorie restriction temporally regulates the hepatic autophagy and redox status in male rat. Free Radical Biology and Medicine, 130, pp.592-600.  30248445 
Berry, J.L., Zhu, W., Tang, Y.L., Krishnamurthy, P., Ge, Y., Cooke, J.P., Chen, Y., Garry, D.J., Yang, H.T., Rajasekaran, N.S. and Koch, W.J., 2019. Convergences of life sciences and engineering in understanding and treating heart failure. Circulation research, 124(1), pp.161-169.  30605412 
Kuster, D.W., Lynch IV, T.L., Barefield, D.Y., Sivaguru, M., Kuffel, G., Zilliox, M.J., Lee, K.H., Craig, R., Namakkal-Soorappan, R. and Sadayappan, S., 2019. Altered C10 domain in cardiac myosin binding protein-C results in hypertrophic cardiomyopathy. Cardiovascular research, 115(14), pp.1986-1997.  31050699 
Goh, K.Y., He, L., Song, J., Jinno, M., Rogers, A.J., Sethu, P., Halade, G.V., Rajasekaran, N.S., Liu, X., Prabhu, S.D. and Darley-Usmar, V., 2019. Mitoquinone ameliorates pressure overload-induced cardiac fibrosis and left ventricular dysfunction in mice. Redox biology, 21, p.101100.  30641298 
Kannappan, R., Turner, J.F., Miller, J.M., Fan, C., Rushdi, A.G., Rajasekaran, N.S. and Zhang, J., 2019. Functionally Competent DNA Damage-Free Induced Pluripotent Stem Cell–Derived Cardiomyocytes for Myocardial Repair. Circulation, 140(6), pp.520-522.  31381423 
Shanmugam, G., Challa, A.K., Devarajan, A., Athmanathan, B., Litovsky, S.H., Krishnamurthy, P., Davidson, C.J. and Rajasekaran, N.S., 2019. Exercise mediated Nrf2 signaling protects the myocardium from isoproterenol-induced pathological remodeling. Frontiers in cardiovascular medicine, 6, p.68.  31245386 
Shanmugam, G., Challa, A.K., Litovsky, S.H., Devarajan, A., Wang, D., Jones, D.P., Darley-Usmar, V.M. and Rajasekaran, N.S., 2019. Enhanced Keap1-Nrf2 signaling protects the myocardium from isoproterenol-induced pathological remodeling in mice. Redox biology, 27, p.101212.  31155513  
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 
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.   
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 
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, 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 
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 
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 
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 
Narasimhan, M. and Rajasekaran, N.S., 2016. Exercise, Nrf2 and antioxidant signaling in cardiac aging. Frontiers in physiology, 7, p.241.  29022266 
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 
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 
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 
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 
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 
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 
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  
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  
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  
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 
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  
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  
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 
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.


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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.


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Keywords
Reductive Stress, Nrf2-Keap1 Signaling, Cardiac Remodeling, Proteotoxicity, Cardiac Aging, Neurodegeneration, Alzheimer's disease