Dhandapani Kuppuswamy, Ph.D.

Dhandapani Kuppuswamy, Ph.D.

Principal Investigator at the Gazes Cardiac Research Institute
Associate Professor of Medicine

Department of Medicine, Division of Cardiology, Gazes Cardiac Research Institute, Medical University of South Carolina, 114 Doughty Street, Charleston, SC 29403

Phone: (843) 876 - 5069 Office / Fax: (843) 876 - 5068
E-mail: kuppusd@musc.edu

EDUCATION:

1971-1975 B.S. Chemistry, Mathematics, Physics; University of Madras, India
1976-1978 M.S. Biochemistry; University of Madras, India
1978-1979 M.Phil.; University of Madras,India
1979-1984 Ph.D. Biochemistry; University of Madras, India; Thesis: Phospholipid and related changes in rat atherosclerosis controlled by Anna Pavala Sindhooram

Postgraduate Education

1981-1982 Junior Research Fellow; Council of Scientific and Industrial Research; University of Madras, India
1982-1984 Senior Research Fellow; Council of Scientific and Industrial Research; University of Madras, India
1984-1986 Postdoctoral Fellow; Department of Biochemistry; Mount Sinai School of Medicine, New York, NY
1986-1991 Research Associate, HHMI; Department of Biochemistry; Washington University School of Medicine; St. Louis, MO
1991-1993 Research Instructor; Department of Biochemistry; Washington University School of Medicine; St. Louis, MO
1993-1994 Research Trainee; Department of Pathology; University of North Carolina at Chapel Hill; Chapel Hill, NC

A major research interest in my laboratory is focused on protein kinase signaling in hypertrophying myocardium:

(i) Protein kinase signaling in hypertrophying myocardium:

      Hypertrophy is the basic adaptive response of the adult heart to hemodynamic overload such as pressure or volume overload. While the initial response to the increased demand of cardiac muscle function is compensated by the hypertrophic growth of the cardiac muscle cell, this functionality fails and results in congestive heart failure (CHF) when the load increase exceeds the growth capacity. Therefore, it is important to identify the intermediate pathways both during the initial compensatory hypertrophy and during the transition into decompensatory hypertrophy resulting in CHF. Our recent experiments in the initial phase of pressure overload-induced cardiac hypertrophy showed the presence of two major signaling pathways:
      (a) During an early period of pressure overload (1 to 4 hr), a signaling cascade that is independent of integrins, occurs with the activation of protein kinase C, c-Raf and p70/85S6K (S6K1). Since S6K1 is important for enhancing the translational capacity of the cell, we are studying the mechanism and role of PKC/c-Raf/MEK/ERK pathway in the activation of S6K1 and in the mobilization of ribosomal mRNA possessing polypyrimidine tract in the 5'-untranslated region (5'-TOP mRNA) into polysomes for protein translation.
     (b) During the later period of pressure overload (4 to 48 hr), an integrin-dependent signaling occurs that results in the cytoskeletal (CSK) assembly and activation of non-receptor tyrosine kinases (focal adhesion kinase (FAK and c-Src) and several adapter proteins (p130Cas, Nck and Shc). To determine the role of this assembly, we have developed a cell culture model in which integrin is activated with Arg-Gly-Asp (RGD) peptide after embedding adult cardiocytes in collagen gel. This model mimics most of our in vivo data on integrin activation and focal complex formation. We are exploring the importance of this activation with respect to hypertrophic growth (possibly for the sustained activation of S6K1) and survival of adult cardiocytes (by the activation of NFkB and STAT3 signaling pathways).

Chris Willey is examining cytoskeletal assembly of signaling proteins in cardiac hypertrophy.

Laboratory Members

Charlene Kerr

Santhosh Mani, Ph.D.

Arun Palanisamy

Bala Sundar

Past Laboratory Members

Yoshihiro Iijima, M.D.

Vijaykumar Kasi, M.D., Ph.D.

Martin Laser

Chris Willey, M.D., Ph.D.

Recent Publications:

Tagawa, H., Roszich, J. D., Tsutsui, H., Narishige, T., Kuppuswamy, D., Sato, H., McDermott, P. J., Koide, M. and Cooper, IV, G. Basis for increased microtubules in pressure hypertrophied cardiocytes. Circulation, 93, 1230-1243 (1996).

Kuppuswamy, D., Kerr, C., Narishige, T., Kasi, V.S., Menick, R., and Cooper, G, IV. Association of tyrosine phosphorylated c-Src with the cytoskeleton of hypertrophying myocardium. J. Biol. Chem., 272, 4500-4508 (1997).

Sato, H., Narishige, T., Kuppuswamy, D., Koide, M., Menick, D.R., and Cooper, G. IV. Microtubule stabilization in pressure overload cardiac hypertrophy. J. Cell Biol., 139, 963-973 (1997).

Laser, M., Kasi, V.S., Hamawaki, Cooper, G., M., Kerr, C.M., and Kuppuswamy, D. Differential activation of p70 and p85 S6 kinase isoforms during cardiac hypertrophy in the adult mammal. J. Biol. Chem., 273, 24610-24619 (1998).

Narishige, T., Blade, K.L., Ishibashi, Y., Nagai, T., Hamawaki, M., Menick, D.R., Kuppuswamy, D., and Cooper, G. IV. Cardiac hypertrophy and developmental regulation of the b-tubulin multigene family. J. Biol. Chem., 274, 9692-9697 (1999).

Nagai, T., Laser, M, Baicu, C.F., Zile, R. M., Cooper, G., and Kuppuswamy, D. b3-Integrin-Mediated Focal Adhesion Complex Formation: Studies of Adult Cardiocytes Embedded in a Three-Dimensional Collagen Matrix. Am. J. Cardiol., 83, 38H-43H (1999).

Kasi, V.S., and Kuppuswamy, D. Inhibition of SRC family kinases by a combinatorial action of 5'AMP and small heat shock proteins, both identified from the adult heart. Mol. Cell. Biol., 19, 6858-6871 (1999).

Laser, M., Willey, C.D., Jiang, W., Cooper, G. 4th, Menick, D.R., Zile, M.R., Kuppuswamy, D. Integrin activation and focal complex formation in cardiac hypertrophy. J Biol Chem. Nov 10; 275 (45): 35624-30 (2000).

Iijima, Y., Laser, M., Shiraishi, H., Willey, D., Sundaravadivel, B., Xu, L., McDermott, P.J., and Kuppuswamy, D. c-Raf/MEK/ERK pathway controls protein kinase C-mediated p70S6K activation in adult cardiac muscle cells. J. Biol. Chem., 277, 23065-23075 (2002).
Kuppuswamy, D Importance of integrin signaling in myocyte growth and survival. Circ. Res., 90, 1240-1242 (2002)
Cheng, G., Iijima, Y., Ishibashi, Y., Kuppuswamy, D., and Cooper, G.: Inhibition of G protein-coupled receptor trafficking in neuroblastoma cells by MAP 4 decoration of microtubules. Am J Physiol Heart Circ Physiol., 283, H2379-2388 (2002)
Basuroy, S., Sheth, P., Kuppuswamy, D., Balasubramanian, S., Ray, R. M., and Rao, R. K. Expression of kinase-inactive c-Src delays oxidative stress-induced disassembly and accelerates calcium-mediated reassembly of tight junctions in Caco-2 cell monolayer. J. Biol. Chem., 278, 11916-11924 (2003)
Willey, C.D, Balasubramanian, S, Rodriguez Rosas, M.C., Ross, R.S., and Kuppuswamy, D. Focal complex formation in adult cardiomyocytes is accompanied by the activation of _3 integrin and c-Src. J. Mol. Cell. Cardiol., 35, 671-683 (2003).
Book Chapters

Laser, M., Nagai, T., Kasi, V. S., Baicu, C. F., Willey, C. W., Kerr, C. M., Zile, M. R., Cooper, G. IV., and Kuppuswamy, D. Integrin -dependent and -independent signaling during pressure overload cardiac hypertrophy. In: The hypertrophied heart: edited by Takeda, N., Nagano, T.M., and Dhalla, N. S. Kluwer Academic Publishers, Boston, 2000. pp. 143-164.

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