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N. Ravi Sundaresan
Assistant Professor
MVSc, PhD (IVRI, Izatnagar, Bareilly, India)
Phone:+91 80 2293 2068
E.mail: rsundaresan@mcbl.iisc.ernet.in

Sirtuins in Cardiovascular diseases

Our lab studies Sirtuins, a family of histone deacetylases. Mammalian genome encodes seven Sirtuin isoforms (SIRT1-SIRT7), which differ in their structures, substrate specificities and subcellular localizations.We study how they regulate the pathophysiology of heart failure induced by hypertension, myocardial infarction and metabolic diseases. We use primary cell cultures, transgenic, dietary and surgical mouse models to test Sirtuins for their ability to protect against cardiovascular disease. Our lab techniques range from physiology and biochemistry, to molecular biology and proteomics. Ongoing work in our lab involves studies of the role of Sirtuins in cardiac hypertrophy, fibrosis, mitochondrial dysfunction and muscle degeneration. Our goal is to disclose new biological functions of Sirtuins that can be therapeutically targeted for promoting health-span of heart.

Selected publications

Sundaresan NR, Vasudevan P, Zhong L, Kim G, Samant S, Parekh V, Pillai VB, Ravindra PV, Gupta M, Jeevananadam V,  Cunningham JM, Deng CX, Lombard DB, Mostoslavsky R, Gupta MP. The sirtuin SIRT6 blocks IGF-Akt signaling and development of cardiac hypertrophy by targeting c-Jun. Nature Medicine 2012, 18(11):1643-50.

Sundaresan NR, Pillai VB, Wolfgeher D, Samant S, Gupta MP, Vasudevan P, Parekh V, Raghuraman H, Cunningham JM, Gupta M  Gupta MP. SIRT1 regulates Akt and PDK1 membrane localization and activation during cell growth associated with tumorigenesis and cardiac hypertrophy. Science Signaling 2011, 4(182):ra46. 

Sundaresan NR, Gupta M, Kim G, Rajamohan SB, Isbatan A, Gupta MP. Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. Journal of Clinical Investigation 2009, 119(9):2758-71.

Sundaresan NR, Samant SA, Pillai VB, Rajamohan SB, Gupta MP. SIRT3 is a stress-responsive deacetylase in cardiomyocytes that protects cells from stress-mediated cell death by deacetylation of Ku70. Molecular and Cellular Biology 2008, 28(20):6384-401.

Sundaresan NR, Pillai VB, Gupta MP. Emerging roles of SIRT1 deacetylase in regulating cardiomyocyte survival and hypertrophy. Journal of Molecular and Cellular Cardiology. 2011, 51:614-8

Pillai VB, Sundaresan NR, Kim G, Gupta M, Rajamohan SB, Pillai JB, Samant S, Ravindra PV, Isbatan A, Gupta MP. Exogenous NAD blocks cardiac hypertrophic response via activation of the SIRT3-LKB1-AMPK pathway. Journal of Biological Chemistry 2010, 285(5):3133-44.

Nagalingam RS, Sundaresan NR, Gupta MP, Geenen D, Solaro RJ, Gupta M. A cardiac enriched microRNA, miR-378 blocks cardiac hypertrophy by targeting Ras-signaling. Journal of Biological Chemistry 2013, 288(16):11216-32.

Pillai VB, Sundaresan NR, Samant S, Wolfgeher D, Trivedi CM, Gupta MP. Acetylation of a conserved lysine residue in the ATP binding pocket of p38 augments its kinase activity during hypertrophy of cardiomyocytes. Molecular and Cellular Biology 2011, 31:2349-63.

Samant SA, Courson DS, Sundaresan NR, Pillai VB, Tan M, Zhao Y, Shroff SG, Rock RS, Gupta MP. HDAC3-dependent reversible lysine acetylation of cardiac myosin heavy chain isoforms modulates their enzymatic and motor activity. Journal of Biological Chemistry. 2011, 286 (7):5567-77.

Knezevic I, Patel A, Sundaresan NR, Gupta MP, Solaro RJ, Nagalingam RS, Gupta M. A novel Cardiomyocyte enriched microRNA, miR-378, targets IGF1R: implications in post natal cardiac remodeling and cell survival. Journal of Biological Chemistry. 2012, 287(16):12913-26.