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OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015) BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FIVE PAGES. NAME: Suresh C. Tyagi eRA COMMONS USER NAME (credential, e.g., agency login): S0TYAG01@LOUISVILLE. POSITION TITLE: Endowed Chair Professor EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.) INSTITUTION AND LOCATION University of Aligarh, India University of Aligarh, India University College, Cork, Ireland SUNY at Stony Brook, NY, USA SUNY at Stony Brook, NY, USA DEGREE (if applicable) M.Phil. Ph.D. Post-Grad Post-Doc Res Assoc Completion Date MM/YYYY 1977 1980 1983 1987 1989 FIELD OF STUDY Chemistry Biophysics Bioinorganic Chemistry Pharmacology Pathology A. Personal Statement: Our lab is one of the leaders in the field of role of MMP/TIMP axis in the muscle biology and extracellular matrix remodeling that play essential role in the replacement or repair of damaged, missing or poorly functioning heart and musculoskeletal tissues, including the skeletal muscle and the cardiac muscle remodeling. Also we have published numerous articles on the role of exercise in mitigation of diabetic complications. Also the role of H2S as protective agents has been studies in our laboratory. Therefore, we are in the situation to execute the experiments proposed in this proposal. B. Positions and Honors: 1989-1991 Instructor, Biochemistry & Cell Biology, SUNY-Stony Brook, New York 1992-1996 Assistant Professor, Medicine & Biochemistry, University of Missouri-Columbia, Missouri 1996-2003 Associate Professor, Physiology & Biophysics, Univ of Mississippi Medical Center, Jackson, MS 2003-present Professor, Physiology & Biophysics, University of Louisville, Louisville, Kentucky 2003-present Stodghill Endowed Chair in Biomedical Sciences, University of Louisville, Louisville, Kentucky 2003-present Vice Chair for Research, Physiology & Biophysics, University of Louisville, Louisville, Kentucky Awards and Professional Activities: 1978-1980 Research Fellowship, University Grants Commission, India 1980-1982 Senior Demonstratorship, University of Cork, Ireland 1991 American Society of Biochemistry & Molecular Biology, Travel Award for the 15th International Congress of Biochemistry, Jerusalem, Israel 1992 International Union of Biochemistry & Molecular Biology, Travel Award for the Ist conference on the Biochemistry of Diseases, Nayoga, Japan 1995 American Heart Association, Boots Cardiovascular Research Prize, Finalist, Feb 1-4, 1995, Snowbird Conference Center, Salt Lake City, Utah 1995 Travel Award, 7th Intern Symp Basement Membrane, NIH-NIDDKD, 06/29-30, 1995. 1998 Astra Merck Faculty Travel Award, Pathophysiology of Myocardial Stunning, Hibernation and Preconditioning, Oct 15-17, 1998, Taormina-SiCily-Italy PHS 398/2590 (Rev. 05/01) Page _______ Biographical Sketch Format Page 2000 AstraZeneca Faculty Travel Award, Euro Society Cardiology, August 26-30, 2000, Amsterdam, 2001 AstraZeneca Apollo Faculty Award. 2001 Medal of Merit, ISHR, XVII World Congress Winnipeg, Canada. Editorial Board, Fellowship and Committee: 2004-2007 Journal of Molecular and Cellular Cardiology;1999- Am J Physiol (Heart & Circulatory Physiology); 2001Clinical & Experimental Hypertension; 2003- Molecular Cellular Biochemistry; Fellowship: 2000-AHA; 2002-APS (Cardiovascular Section); Member of APS-Fellowship Committee (2003-2006); Awards Committee (2006-2009). Study Section Member: 1997-2005 AHA Southeast-Ohio Valley (Vascular Biology); 2000-2003 AHA National (Molecular Signal I); NIH 2003 RFA; NIH-ECS; 2004 PPG; VCMB; NCI-IMAT; 2005-NIAMS; ESTA; RFA-NIDDK; 2006-2010-MIM; NIH/BINP/MTE/SBIR/HM/SEP/grant reviewer (Ad Hoc) 2000 - present C. Contributions to Science: 1. Our lab is the FIRST to discover the activation of latent matrix metalloproteinases (MMPs) in the heart. a) Tyagi SC. Matsubara L, Ratajska A, Weber KT. Identification and localization of myocardial collagenases(s), Clin Res, 40:757A, 1992. b) Tyagi SC, Matsubara L & Weber KT. Direct extraction and estimation of callagenase(s) activity by zymography in microquantities of rat myocardium and uterus, Clin Biochem, 26:191-198, 1993. c) Tyagi SC & Cleutjens JPM. Myocardial collagenase: purification and structural characterization, Canad J Cardiol, 12:165-171, 1995. d) Tyagi SC, Kumar SG, Banks J & Fortson W. Co-expression of Tissue Inhibitor and Matrix Metalloproteinase in Myocardium, J Mol Cell Cardiol, 27:2177-2189, 1995. 2. The term myocardial remodeling was coined in our laboratory by identifying the MMPs in the heart and MMP functional proteome was discovered in my laboratory by running the first 2-D zymographic gel in the world. a) Tyagi SC, Haas SJ, Kumar SG, Reddy HK, Voelker DJ, Hayden MR, Demmy TL, Schmaltz RA & Curtis JJ. Post-trancriptional regulation of extracellulr matrix metalloproteinse in human heart endstage failure secondary to ischemic cardiomyopathy, J Mol Cell Cardiol, 28:1415-1428, 1996. b) Tyagi SC, Kumar SG, Alla SR, Reddy HK, Voelker DJ & Janicki JS. ECM Regulation of Metalloproteinase & Antiproteinase in Human Heart Fibroblasts, J Cell Physiol, 167:137-147, 1996. c) Tyagi SC, Kumar SG, Voelker DJ, Reddy HK, Janicki JS & Curtis JJ. Differntial gene expression of extracellular matrix components in dilated cardiomyopathy, J Cell Biochem, 63:185-198, 1996. d) Tyagi SC, Lewis K, Pikes D, Marcello A, Mujumdar V, Smiley L, Moore CK. Stretch induced membrane type matrix metalloproteinases and tissue plasminogen activator in cardiac fibroblast cells, J Cell Physiol, 176:374-382, 1998. e) Miller A, Mujumdar V, Shek E, Guillot J, Angelo M, Pakmer L, Tyagi SC. Hyperhomocysteinemia induces multiorgan damage, Heart & Vessels, 15(3):135-143, 2000. 3. We were the first to discover decrease in elastin/collagen ratio in atherosclerosis. a) Tyagi SC, Meyer L, Schmaltz RA, Reddy HK & Voelker DJ. Proteinases and Restenosis in Human Coronary Artery: Extracellular Matrix Production Exceeds the Expression of Proteolytic Activity, Atherosclerosis, 116:43-57, 1995. b) Tyagi SC. Homocysteine redox receptor and regulation of extracellular matrix components in vascular cells, Am J Physiol, 274:C396-C405, 1998. c) Tummalapalli CM, Tyagi SC. Response of vascular smooth muscle cells to extracellular matrix degradation, J Cell Biochem, 75:515-527, 1999. d) Cox MJ, Hawkins UA, Hoit BD, Tyagi SC. Attenuation of oxidative stres and remodeling by cardiac inhibitor of metalloproteinase protein transfer, Circulation, 109(17):2123-2128, 2004. 4. We are the first to identify the tissue levels of homocysteine in atherosclerotic plaques. a) Tyagi SC, Smiley LM, Mujumdar VS, Clonts B, Parker JL. Reduction-oxidation (redox) and vascular tissue level of homocyst(e)ine in human coronary atherosclerotic lesions and role in vascular extracellular matrix remodeling and vascular tone, Mol Cell Biochem, 181:107-116, 1998. b) Tyagi SC. Homocysteine redox receptor and regulation of extracellular matrix components in vascular cells, Am J Physiol, 274:C396-C405, 1998. c) Mujumdar VS, Aru GM, Tyagi SC. Induction of oxidative stress by homocyst(e)ine impairs endothelial function, J Cell Biochem, 82(3):491-500, 2001 d) Sood HS, Cox MJ, Tyagi SC. Generation of Nitrotyrosine Precedes the Activation of Matrix Metalloproteinase in Left Ventricle of Hyperhomocystenemia Rats, Antioxidant & Redox Signaling, 4(5):799-804, 2002. PHS 398/2590 (Rev. 05/01) Page _______ Biographical Sketch Format Page Complete List of Published Work in PubMed: http://www.ncbi.nlm.nih.gov/pubmed/?term=Tyagi+SC%2C D. Research Support: 2R01 HL-74185, 250,000/year direct cost, Tyagi-PI 9/1/2003-2/1/2019 “Reversing diabetic muscle myopathy by exercise and exosomes”. The major goals of this project are to study cardiac endothelial myocyte function in chronic left ventricular volume overload heart failure. R01 HL108621, 250,000/year direct cost, Tyagi-PI 4/1/2011-12/31/2016 “Mitogenic and anti-angiogenic mechanisms of heart failure”. The major goals of this project are to study angiogenesis and mitochondrial mitophagy in chronic left ventricular pressure overload heart failure. RO1 NS-84823, 170,000/year, Tyagi-MPI 7/1/1913-6/30/2018 "Mechanisms of Homocysteine-induced FibrinogenAmyloid Plaque Formation”. The major goal of this project is determine role of homocysteine in vascular dementia and Alzheimer. RO1 DK 104653-01, 180,000/year Tyagi-MPI, 07/01/2015-06/30/2020 “Hydrogen sulfide mechanism of renal hypertension”. The major goal of this project is to determine mechanism of renal remodeling and role of H2S. RO1 AR067667-01, 190,000/year Tyagi-MPI, 09/01/2015-08/31/2020 “Mitigating mitochondrial epigenetics in bone remodeling by hydrogen sulfide”. The major goal of this project is to determine the mechanism of bone remodeling and epigenetics. PHS 398/2590 (Rev. 05/01) Page _______ Biographical Sketch Format Page