Sachin Gupte, M.D., Ph.D.
Associate Professor of Pharmacology
Department of Pharmacology
Basic Science Building, Rm. 546
15 Dana Road
Valhalla, NY 10595
Tel: (914) 594-3937
The long-term goals of our translational research program are: 1) to study the pathogenesis; and 2) to develop new therapies for three human diseases – pulmonary arterial hypertension (PAH), PAH-induced heart failure, and metabolic syndrome-associated coronary artery disease (MS-CAD). Our laboratory has recently discovered that two isoenzymes of glucose-6-phosphate dehydrogenase (G6PD) are expressed in the vascular smooth muscle (VSM) and G6PD-derived NADPH (pyridine nucleotide) signaling play a role in mediating VSM contraction and switching VSM cell from contractile to synthetic phenotype. Currently, we are exploring the G6PD/pyridine nucleotide-dependent novel signal transduction pathways involved in epigenetic modifications of gene function/regulation. Another goal of our laboratory is to study the role of G6PD-derived NADPH in the regulation of protein structure-function that contribute to the VSM remodeling and increased vascular resistance in PAH and MS-CAD. We are also examining the role of pyridine nucleotide signaling in regulating extracellular matrix remodeling and autophagic or apoptotic death of cardiomyocytes during the development of heart failure in PAH. Overall, our aim will be to study the metabolic adaptation-cardiovascular function relationship using biochemical, molecular, pharmacological and genetic approaches in novel animal models and in vitro systems that mimic human diseases and to explore novel therapies for PAH and MS-CAD.
- Gupte S.A., Okada T., McMurtry I.F., Oka M. Role of pentose phosphate pathway-derived NADPH in hypoxic pulmonary vasoconstriction. Pulmonary Pharmacology & Therapeutics. 2006; 19: 303-309.
- Gupte R.S., Floyd B.C., Kozicky M., George S., Neito V., Agrawal R., Wolin M.S., Gupte S.A. Synergistic Role of Glucose-6-Phosphate Dehydrogenase and NAD(P)H oxidase in Elevating Liver Oxidative Stress & Hypertrophy in Type 2 Diabetic, Zucker fa/fa, Rat. Free Radical Biology & Medicine. 2009; 47: 219-228. PMCID: PMC2700195
- Serpillon, S., Floyd B.C., Gupte R.S., George S., Kozicky. M., Neito V., Recchia F., Stanley W., Wolin M.S., Gupte S.A. Superoxide production by NAD(P)H oxidase and mitochondria is increased in genetically obese and hyperglycemic rat heart and aorta before the development of cardiac dysfunction. The role of glucose-6-phosphate dehydrogenase-derived NADPH American Journal of Physiology (Heart and Circulation). 2009; 297: H153-H162. PMCID: PMC2711743
- Gupte R.S., Rawat D.K., Chettimada S., Cioffi D.L., Wolin M.S., Gerthoffer W.T., McMurtry I.F., Gupte S.A. Activation of glucose-6-phosphate dehydrogenase promotes acute hypoxic pulmonary artery contraction. Journal of Biological Chemistry. 2010; 285: 19561-19571. PMCID: PMC2885235
- Gupte R.S., Ata H., Rawat D.K., Abe M., Taylor M.S., Ochi R, Gupte, S.A. Glucose-6-Phosphate Dehydrogenase is a Regulator of Vascular Smooth Muscle Contraction. Antioxidant Redox Signaling. 2011: 543-58. PMCID: PMC3029003
- Ata H, Rawat DK, Lincoln TM, Gupte SA. Mechanism of Glucose-6-Phosphate Dehydrogenase-mediated Regulation of Coronary Artery Contractility. American Journal of Physiology (Heart and Circulation). 2011; H2054-H2063. PMCID: PMC3119095
- Chettimada S, Rawat D.K., Dey N,Kobelja R, Simms Z, Ata H, Wolin M.S., Lincoln T.M.,Gupte S.A. Glucose-6-Phosphate Dehydrogenase and Protein Kinase G Contribute to Hypoxia-Induced Pulmonary Artery Smooth Muscle Cell Phenotypic Changes. American Journal of Physiology (Lung Cellular & Molecular). 2012; 303: L64-L74. PMCID: PMC3426433
- Rawat DK, Hecker P, Watanabe M, Chettimada S, Levy RJ, Okada T, Edwards JG, Gupte SA. Glucose-6-phosphate dehydrogenase and NADPH redox regulates cardiac myocyte L-type calcium channel activity and myocardial contractile function. PLoS One. 2012; 7: e45365. PMCID: PMC3465299
- Chettimada S, Ata H, Rawat DK, Gulati S, Kahn AG, Edwards JG, Gupte SA. MicroRNA-145 and Contractile Protein Expression is Upregulated by Reactive Oxygen Species in Aorta of Goto-Kakizaki Rat. American Journal of Physiology (Heart and Circulation). 2014 Jan 15;306(2):H214-24.
- Sukrutha Chettimada, Sachindra Raj Joshi, Abdallah Al Zoubi, Sarah A Gebb, Masahiko Oka, Ivan F McMurtry, Rakhee Gupte, Sachin A Gupte. Glucose-6-phosphate dehydrogenase plays a critical role in hypoxia-induced CD133+ progenitor cells self-renewal and stimulates their accumulation in the lungs of pulmonary hypertensive rats. American Journal of Physiology (Lung Cellular & Molecular). 2014; 307(7): L545-556.
- Dhawjbahadur K Rawat, Abdallah Alzoubi, Rakhee Gupte, Sukrutha Chettimada, Makino Watanabe, Andrea G Kahn, Takao Okada, Ivan F McMurtry, Sachin A Gupte. Increased reactive oxygen species, metabolic maladaptation and autophagy contribute to pulmonary arterial hypertension-induced ventricular hypertrophy and diastolic heart failure. Hypertension. 2014; 64(6): 1266-1274.
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