Dr. Laxmansa C. Katwa, Ph.D.  | Associate Professor
Department of Physiology
| Phone: (252) 744-1906 Fax: (252) 744-3460 E-mail: katwal@ecu.edu Mailing Address: Brody School of Medicine, 6N-73C 600 Moye Blvd. Greenville, NC 27834
Research Interests For the last several years our lab has been focusing on elucidating the molecular signaling and cellular mechanisms of key vasoactive peptides (angiotensin II, endothelin, urotensin II and VEGF) in cardiac tissue remodeling and fibrosis. Cardiac myofibroblasts (MyoFb) are key wound healing fibroblast-like cells that appear in response to injury following myocardial infarction and possess morphologic features of both smooth muscle cells and fibroblasts. These cells express various pro-remodeling cytokines and are involved in high collagen turnover, cardiac tissue repair/remodeling, and fibrosis. They are therefore the most prudent cells types to study when examining the interstitial collagen build-up in cardiac tissue. This interstitial collagen build-up causes scarring and changes in the shape of the left ventricle, which significantly affects the efficiency of the heart and leads to cardiac dysfunction and failure.
Recently, we and others have shown that activation of PPAR-Ÿ (peroxisome proliferator-activated receptor-gamma, a nuclear receptor) signaling inhibits collagen production and reduces fibrosis, helps down-regulate the inflammatory cytokine NF-kb pathway, and induces angiogenesis via stimulating the production of VEGF and its receptors. All of these effects are beneficial to the heart and aid in its recovery following MI. Our lab is interested in elucidating the fine molecular mechanisms by which PPAR-Ÿ signaling occurs in MyoFb under such pathological conditions in the hope of expanding the potential targets designed to inhibit cardiac remodeling/fibrosis following MI.
Currently we are focusing on two aspects of PPAR-Ÿ signaling, VEGF up-regulation, and inhibition of collagen expression. First, we have found that PPAR-Ÿ causes the up-regulation of the pro-angiogenic factor VEGF and are currently working to uncover the specific signaling pathway through which this occurs. Second, we are working to uncover the role of several key pro-remodeling factors (ANGII, TGF-β, ET) and transcription factors (SMAD, STAT, and SP1) in mediating PPAR-Ÿ's inhibition of collagen expression. Additionally, we are looking to see both whether any cross-talk exists between these factors and whether they interact with the VEGF signaling pathway.
Lastly, our lab, in conjunction with the division of cardiology, is currently involved in a collaborative research study with UCLA (funded by the California Air Resources Board) looking to see if there is a change in the serum levels of cardiovascular markers in a study investigating "the cardiovascular health effects of air pollution (fine and ultrafine particles) exposure to humans during freeway travel" (March 2006-Feb 2008).
Employment/Education Associate Professor (2004 - Present)
Physiology & Associate Professor of Cardiovascular Center
Brody School of Medicine
East Carolina University, Greenville, NC
Research focus: Cardiac Remodeling Following Myocardial Infarction Assistant Professor (1999 - 2004)
Physiology & Associate Professor of Cardiovascular Center
Brody School of Medicine
East Carolina University, Greenville, NC Research Associate Professor (1998 - 1999)
Biomedical Sciences, Dept. of Vet
University of Missouri, Columbia, MO Assistant Professor (1993 - 1998)
Division of Cardiology
Department of Medicine
University of Missouri, Columbia, MO Research Assistant Professor (1992 - 1993)
Division of Cardiology
Departent of Medicine
University of Missouri, Columbia, MO Post-Doctoral Fellow/Research Associate (1988 - 1992)
Dalton Research Center
University of Missouri, Columbia, MO Assistant Professor (1985 - 1986)
Department of Biochemistry
JSS Medical School
Mysore, India Doctor of Philosophy, Biochemistry (1977 - 1979)
Karnatak University
Dharwar, India Bachelor of Science, Chemistry (1973 - 1977)
Karnatak University
Dharwar, India
Grants Principal Investigator
NIH R01 Endothelin Induced Cardiac Collagen Expression, July 1999 - June 2005
Principal Investigator
American Heart Association, Grant-In-Aid, National
Endothelins in Mineralocortoid Induced Vascular Remodeling, July 1996 - June 2000 Co-Investigator
NIH R01 Exercise, Diabetes, Smooth Muscle Caa++, April 1999 to March 2004 NIH R01 RFA
Th1 to Th2 Shifts of HSP-65 Responses and Atherosclerosis, October 2002 - September 2006
Publications Harris GS, Lust RM, Katwa LC. Hemodynamic effects of chronic urotensin II administration in animals with and without aorto-caval fistula. Peptides. 2007 Aug;28(8):1483-1489. Chintalgattu V, Harris GS, Akula SM, Katwa LC. PPAR-gamma agonists induce the expression of VEGF and its receptors in cultured cardiac myofibroblasts. Cardiovasc Res. 2007 Apr 1;74(1):140-150.
Murashov AK, Chintalgattu V, Islamov RR, Lever TE, Pak ES, Sierpinski PL, Katwa LC, Van Scott MR. RNAi pathway is functional in peripheral nerve axons. FASEB J. 2007 Mar;21(3):656-670.
Morrison RR, Teng B, Oldenburg PJ, Katwa LC, Schnermann JB, Mustafa SJ. Effects of targeted deletion of A1 adenosine receptors on postischemic cardiac function and expression of adenosine receptor subtypes. Am J Physiol Heart Circ Physiol. 2006 Oct;291(4):H1875-1882. Murashov AK, Pak ES, Katwa LC. Parallel development of cardiomyocytes and neurons in embryonic stem cell culture. Biochem Biophys Res Commun. 2005 Jul 8;332(3):653-656. Beckman DL, Cummings JJ, Katwa LC, Whitehurst ME. Can maternal vitamin e supplementation prevent lung hypoplasia in the nitrofen-induced rat model of congenital diaphragmatic hernia? Pediatr Res. 2005 Mar;57(3):392-395. Islamov RR, Chintalgattu V, Pak ES, Katwa LC, Murashov AK. Induction of VEGF and its Flt-1 receptor after sciatic nerve crush injury. Neuroreport. 2004 Sep 15;15(13):2117-2121. Chintalgattu V, Katwa LC. Role of protein kinase Cdelta in endothelin-induced type I collagen expression in cardiac myofibroblasts isolated from the site of myocardial infarction. J Pharmacol Exp Ther. 2004 Nov;311(2):691-699. Islamov RR, Chintalgattu V, McMurray RJ, Pak ES, Murashov AK, Katwa LC. Differential expression of endothelin receptors in regenerating spinal motor neurons in mice. Brain Res Mol Brain Res. 2003 Aug 19;116(1-2):163-167. Katwa LC. Cardiac myofibroblasts isolated from the site of myocardial infarction express endothelin de novo. Am J Physiol Heart Circ Physiol. 2003 Sep;285(3):H1132-1139. Chintalgattu V, Nair DM, Katwa LC. Cardiac myofibroblasts: a novel source of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and KDR. J Mol Cell Cardiol. 2003 Mar;35(3):277-286. Lee DL, Wamhoff BR, Katwa LC, Reddy HK, Voelker DJ, Dixon JL, Sturek M. Increased endothelin-induced Ca2+ signaling, tyrosine phosphorylation, and coronary artery disease in diabetic dyslipidemic Swine are prevented by atorvastatin. J Pharmacol Exp Ther. 2003 Jul;306(1):132-140. Islamov RR, Hendricks WA, Katwa LC, McMurray RJ, Pak ES, Spanier NS, Murashov AK. Effect of 17 beta-estradiol on gene expression in lumbar spinal cord following sciatic nerve crush injury in ovariectomized mice. Brain Res. 2003 Mar 14;966(1):65-75.
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