Associate Professor,
Department of Surgery
Biological Science Division
Committee on Molecular Medicine and Pathology
5841 S. Maryland Avenue, MC 5040, Room E-500
Chicago, IL 60637
Phone: 773-834-7811
Email:
Education
MSc, All-India Institute of Medical sciences (cum laude), New
Delhi, 1981;
PhD, Pharmacology and Therapeutics, All-India Institute of Medical sciences,
New Delhi, 1985;
Post-doctoral training, The University of Chicago, Mentor Prof. Radovan
Zak
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Neonatal rat heart muscle cell stained for actinin and HDAC4
Nuclear localization of HDAC4
Adult rabbit cardiomyocyte stained for HDAC4
Cytoplasmic localization of HDAC4
Our Lab
Primary focus of my lab is to understand the molecular basis of heart failure, particularly, the role played by the chromatin remodeling enzymes in muscle gene dys regulation, contractile dysfunction and cell-death during heart failure.
Heart failure is a pathological state in which the heart is unable to pump blood at a rate commensurate with the requirements of the metabolizing tissues. It is usually caused by a defect in myocardial contraction. Reduced myocardial contractile function may reflect a decrease in the number of viable myocytes, dysfunction of viable myocytes, or alterations to the intrinsic contractile activity of individual myocytes. At the molecular level, several abnormalities have been observed, including alterations in the expression of numerous genes that are central to the normal structure and function of the myocardium; however, the basic mechanism of heart failure is not yet fully understood. With recent advancements in cell biology, it has become clear that factors modifying chromatin structure, e.g. histone deacetylases, acetyltransferases and poly (ADP) polymerases play a fundamental role in this process. In addition to modifying chromatin structure, these enzymes also play a role out side the nucleus. We are trying to understand how these enzymes modify cytosolic proteins and regulate the cell-survivability and contractile function, in response to various physiologic and pathologic stresses.
Mouse heart sections stained for actinin and HDAC4
Gupta, M.P., Gupta, M., Zak, R., and Sukhatme, V.P. Egr-1, a serum-inducible zinc finger protein regulates transcription of the rat cardiac alpha-myosin heavy chain gene. J. Biol. Chem. 266: 12813-12816, 1991. (PubMed)
Gupta, M.P., Gupta, M. and Zak, R. An E-box/M-CAT hybrid motif and cognate binding protein(s) are required for the basal muscle-specific and cAMP-inducible expression of the rat cardiac alpha-myosin heavy chain gene. J. Biol. Chem. 269: 29677-29687, 1994. (PubMed)
Gupta, M.P., Amin, C.S., Gupta, M., Hay, N., and Zak, R. Transcription enhancer factor-1 interacts with a basic helix-loop-helix zipper protein, Max, for positive regulation of the cardiac alpha-myosin heavy chain gene expression. Mol. Cell. Biol. 17: 3924-3936, 1997. (PubMed)
Gupta, M., Zak R., Liebermann, T.W., and Gupta, M.P. Tissue-restricted expression of the cardiac alpha-myosin heavy chain gene is controlled by a down-stream repressor element containing a palindrome of two Ets-binding sites. Mol. Cell. Biol. 18: 7243-7258, 1998. (PubMed)
Gupta, M., Kogut, P., Davis, F.J., Belaguli, N.S. Schwartz, R.J and Gupta, M. P. Physical interaction between the MADS box of serum response factor and the TEA/ATTS DNA-binding domain of transcription enhancer factor-1. J. Biol. Chem. 276:10413-10422, 2001. (PubMed)
Davis, F.J., Gupta, M., Camoretti-Mercado, B, Schwartz, R.J. and Gupta, M.P. Calcium/calmodulin-dependent protein kinase activates serum response factor transcription activity by its dissociation from histone deacetylases, HDAC4: implications in cardiac muscle gene regulation during hypertrophy. J. Biol. Chem. 278: 20047-20058, 2003. (PubMed)
Gupta, M.P., Kogut, P., and Gupta, M. Protein Kinase-A dependent phosphorylation of transcription enhancer factor-1 represses its DNA-binding activity but enhances its gene activation ability. Nucleic Acids Res. 28: 3168-3177, 2000. (PubMed)
Davis,F.J., Gupta, M., Pogwizd, S.M., Bacha, E, Jeevanandam, V. and Gupta, M.P. Increased expression of alternatively spliced dominant negative Isoform of SRF in human failing hearts. Am. J. Phyisiology 282: H1512-1533, 2002. (PubMed)
Gupta, M., Sueblinvong, V., Raman, J., Jeevanandam, and Gupta, M.P. Single-strand DNA-binding proteins, PURalpha and PURbeta, bind to a purine-rich negative regulatory element of the alpha-myosin heavy chain gene and control transcriptional and translational regulation of the gene expression: Implications in the repression of alpha-MHC during heart failure. J. Biol. Chem 278: 44935-44948, 2003. (PubMed)
Pillai, J.B., Russell, H.M., Raman, J, Jeevanandam, V., and Gupta, M.P. Increased expression of poly (ADP) ribose polymerase-1 contributes to caspase-independent myocyte cell-death during heart failure. Am. J. Physiology 288:H486-H496, 2004. (PubMed)
Davis, F.J., Pillai, J.B., Gupta, M. and Gupta, M.P. Concurrent opposite effects of an inhibitor of histone deacetylases, Trichostatin-A, on the expression of alpha-myosin heavy chain and cardiac tubulins: Implication for gain in cardiac muscle contractility. Am. J. Physiology 288:H1477-H1490, 2005. (PubMed)
Pillai, JB, Isbatan A, Imai SI and Gupta MP. Poly (ADP-ribose) polymerase-1 dependent cardiac myocyte cell-death during heart failure is mediated by NAD+ depletion and reduced activity of the Sir2alpha deacetylase. J. Biol. Chem. 280:43121-43130, 2005. (PubMed)
Pillai, JB, Davis, FJ, Isbatan A and Gupta MP. Mice lacking PARP-1 gene are resistant from angiotensin-II mediated cardiac hypertrophy. Am. J. Physiololgy 291:H1545-1553, 2006.
Han YJ, Hu WY, Chernaya O, Antic N, Gu L, Gupta M, Piano M, de Lanerolle P. Increased myosin light chain kinase expression in hypertension: Regulation by serum response factor via an insertion mutation in the promoter. Mol Biol Cell. 17: 4039-50, 2006. (PubMed)
Paroni, G., Fontanini A, Carnotta N, Foti C, Gupta, MP, Yang XJ, Fasino D and Brancolini C. Dephosphorylation and caspase processing generate distinct nuclear pools of histone deacetylase 4. Mol Cell Biol. 27: 6718-32, 2007. (PubMed)
Gupta, MP. Factors controlling cardiac myosin isoform shift during hypertrophy and heart failure. J. Mol. Cell. Cardiol. 43: 388-403, 2007. (PubMed)
