University of California, Berkeley, Calif., A.B. (1980) and Ph.D. (1986)
Cardiovascular Research Institute, University of California, San Francisco, Calif., Postdoctoral Fellow (1986-1989).
Professor, Dept. of Medicine (Divison of Cardiology), 2007-present
Professor, Dept. of Physiology and Biophysics, Case Westerm Reserve University, Cleveland, OH, 2004-2006
Associate Professor, Dept. of Physiology and Biophysics, Case Westerm Reserve University, Cleveland, OH, 2002-2004
Assistant Professor, Dept. of Physiology and Biophysics, Case Westerm Reserve University, Cleveland, OH, 1996-2002
Director of Development Pharmacologys, CV Therapeutics, Palo Alto, CA, 1995-96
Research Section Leader, Sytnex Discovery Research, Palo Alto, CA, 1992-1995
Assistant Professor, University of Wisconsin, Madison, 1989-1992
Associate Editor, American Journal of Physiology (Heart and Circulator Physiology), 2005-present
Associate Editor, Cardiovascular Drugs and Therapies, 2006-present
President, Society for Heart and Vascular Metabolism, 2002-2006
Program Committee, Heart Failure Society of America, 2007-present
Research InterestsOur lab addresses questions regarding the role of substrate metabolism and diet in the pathophysiology of heart failure and acute ischemic events using broad systems approach. We assess cardiac function and metabolic fluxes in vivo, and evaluate effects on the regulation of gene expression, protein function, pathway fluxes and cardiac function and structure. Much of our work is focused on the development of novel therapies to prevent and treat heart failure and ischemic heart disease. In addition, we study the basic mechanisms that regulate intermediary metabolism and myocardial energetics.
Okere IC, McElfresh TA, Brunengraber DZ, Martini W, Sterk JP, Huang H, Chandler MP, Brunengraber H, Stanley WC. Differential effects of heptanoate and hexanoate on myocardial citric acid cycle intermediates following ischemic/reperfusion. J Appl Physiol 100:76-82, 2006.
Morgan EE, YoungME, McElfresh TA, Kung TA, Hoit BD, Stanley WC, Chandler MP. Chronic activation of peroxisome proliferator activated receptor alpha or high fat feeding alters myocardial lipid metabolism but does not affect contractile function in heart failure. Am J Physiol Heart Circ Physiol. 290: H1899-H1904, 2006.
Morgan EE, Chandler MP, YoungME, McElfresh TA, Kung TA, Hoit BD, Stanley WC. Dissociation between gene and protein expression of metabolic enzymes in a rodent model of heart failure. Euro J Heart Failure 8:687-693, 2006
d'Agostino C, Labinskyy V, Lionetti V, Chandler MP, Lei B, Matsuo K, Bellomo M, Hintze TH, Stanley WC, Recchia FA. Altered cardiac metabolic phenotype after prolonged inhibition of NO synthesis in chronically instrumented dogs. Am J Physiol 290: H1721-H1726, 2006.
Okere IC, Chandler MP, McElfresh TA, Rennison JH, Sharov V, Sabbah HN, Tserng KY, Hoit BD, Ernsberger P, Young ME, Stanley WC. Differential effects of saturated and unsaturated fatty acid diets on cardiomyocyte apoptosis, adipose distribution, and serum leptin. Am J Physiol 291:H38-44, 2006.
Zhou L, Cabrera ME, Okere IC, Sharma N, Stanley WC. Regulation of myocardial substrate metabolism during increased energy expenditure: insights from computational studies. Am J Physiol Heart Circ Physiol 291:1036-1046, 2006.
Morgan EE, YoungME, McElfresh TA, Kung TA, Hoit BD, Chandler MP, Stanley WC. Chronic treatment with trimetazidine reduces the up-regulation of atrial naturetic peptide in heart failure. Fund Clin Pharmacol 20:503-505, 2006.
Okere IC, Young ME, McElfresh TA, Chess DJ, Sharov V, Sabbah HN, Hoit BD, Ernsberger P, Chandler MP, Stanley WC. A low carbohydrate/high fat diet attenuates ventricular hypertrophy, remodeling, and switching of gene expression with hypertension. Hypertension 48:1116-1123, 2006.
Faulx MD, Chandler MP, Zawaneh MS, Stanley WC, Hoit BD. Strain influences myocardial metabolic enzyme activity in mice with isoproterenol-induced cardiac hypertrophy. Clin Exp Physiol Pharmacol 34: 77-80, 2007.
Okere IC, Chandler MP, McElfresh TA, Rennison JH, Kung TA, Tserng KY, Hoit BD, Ernsberger P, Young ME, Stanley WC. Inhibition of carnitine palmitoyltransferase is not associated with cardiac dysfunction in rats fed a high fat diet. Clin Exp Physiol Pharmacol 34, 113-119, 2007.
Zhou L, Cabrera ME, Huang H, Yuan CL, Duda M, Sharma N, Bian F, Stanley WC. Parallel activation of mitochondrial oxidative metabolism with increased cardiac energy expenditure is not dependent on fatty acid oxidation. J Physiol (London) 579:811-821, 2007
Sharma N, Okere IC, Duda MK, Johnson J, Yuan C, McElfresh TA, Chandler MP, Ernsberger PR, Hoit BD, Stanley WC. High fructose diet increases mortality in hypertensive rats compared to a high fat or complex carbohydrate diet. Am J Hypertension 20:403-409, 2007.
Wang X, Stanley WC, Brunengraber H, Kasumov T. Assay of the activity of malonyl-CoA decarboxylase by gas chromatography-mass spectrometry. Analytical Biochemistry 363:169-174, 2007.
Labinsky V, Bellomo M, Chandler MP, Young ME, Lionetti V, Qanud K, Bigazzi F, Sampietro T, Stanley WC, Recchia FA. Chronic activation of PPAR alpha with fenofibrate prevents alterations in cardiac metabolic phenotype without changing the progression of pacing-induced heart failure. J Pharmacol Exp Therap 321:165-171, 2007.
Imai M, Rastogi S, Sharma N, Chandler P, Blackburn B, Belardinelli L, Stanley WC, Sabbah HN. CVT-4325 inhibits myocardial fatty acid uptake and improves left ventricular systolic function without increasing myocardial oxygen consumption in dogs with chronic heart failure. Cardiovasc Drugs Therapies 21:9-15, 2007.
King KL, Young ME, Kerner J, Huang H, O'shea KM, Alexson SE, Hoppel CL and Stanley WC. Diabetes and activation of peroxisome proliferator activated receptor alpha increase mitochondrial thioesterase I protein expression and activity in the heart. J Lipid Res, 2007; 48:1511-1517.
Imai M, Rastogi S, Gupta RC, Mishra S, Sharov VG, Stanley WC, Mika Y, Yuval M, Rousso B, Burkhoff D, Ben-Haim S, Sabbah HN. Therapy with cardiac contractility modulation electrical signals improves left ventricular function and remodeling in dogs with chronic heart failure. J Am Coll Cardiol. 2007;49:2120-2128.
Chess DJ, Lei B, Hoit BD, Azimzadeh AM, Stanley WC. Sugar consumption exacerbates cardiac remodeling, contractile dysfunction, and mortality in response to pressure overload Am J Physiol 293: H1853-H1860, 2007.
Duda MK, O'Shea KM, Lei B, Barrows BR, Azimzadeh AM, McElfresh TE, Hoit BD, Kop WJ, Stanley WC. Dietary supplementation with omega-3 polyunsaturated fatty acids increases plasma adiponectin and prevents ventricular remodeling and dysfunction with pressure overload. Cardiovasc Res 76:303-310, 2007.
King KL, Stanley WC, Kerner J, Rosca M, Hoppel CL, Febbraio M. Fatty acid oxidation in cardiac and skeletal muscle mitochondria is unaffected by deletion of CD36. Arch Biochem Biophys 467:234-238, 2007.
Kung TA, Egbejimi O, Cui J, Durgan DJ, Essop MF, Shaw CA, Hardin PE, Stanley WC, Young ME. Rapid attenuation of circadian clock gene oscillations in the heart following ischemia. J Molec Cell Cardiol 43: 744-753, 2007.
Neglia D, De Caterina A, Marraccini P, Natali A, Ciardetti M, Vecoli C, Gastaldelli A, Ciociaro D, Pellegrini P, Gorini I, Testa R, Menichetti L, L'Abbate A, Stanley WC, Recchia FA. Impaired myocardial metabolic reserve and substrate selection flexibility during stress in patients with idiopathic dilated cariomyopathy. Am J Physiol (Heart Circ Physiol) 293: H3270-H3278, 2007. (accompanying editorial: 293: H3225-H3226, 2007)
Sharma N, Okere IC, Duda M, Chess DJ, O'Shea K, Stanley WC. Potential impact of carbohydrate and fat intake on cardiac hypertrophy. Cardiovasc. Res 73:257-268, 2007.Lopaschuk GD, Folmes CDL, Stanley WC. Cardiac energy metabolism is obesity. Circ Res 101:335-347, 2007.
Chess DJ, Stanley WC. Role of diet and fuel overabundance in the development and progression of heart failure. Cardiovasc. Res 79:269-278, 2008.
Chess DJ, Lei B, Hoit BD, Azimzadeh AM, Stanley WC. Effects of a high saturated fat diet on cardiac hypertrophy and dysfunction in response to chronic pressure overload. J Cardiac Failure 14:82-88, 2008.
Zhou L, Huang H, Yuan CL, Keung W, Lopaschuk GD, Stanley WC. Metabolic response to an acute jump in cardiac workload: effects on malonyl-CoA, mechanical efficiency, and fatty acid oxidation. Am J Physiol (Heart Circ Physiol) 294:954-960, 2008.
Duda MK, O'Shea KM, Lei B, Barrows BR, Azimzadeh AM, McElfresh TE, Hoit BD, Kop WJ, Stanley WC. Low carbohydrate/high fat diet attenuates pressure overload induced ventricular remodeling and dysfunction. J Cardiac Failure 14:327-335, 2008.
Sharma N, Okere IC, Barrows BR, Lei B, Duda MK, Yuan CL, Previs SF, Sharov VG, Azimzadeh AM, Ernsberger P, Hoit BP, Sabbah HN, Stanley WC. High sugar diets increase cardiac dysfunction and mortality in hypertension compared to low carbohydrate or high starch diets. J. Hypertension 26:1402-1410, 2008.
Yuan CL, Sharma N, Gilge DA, Stanley WC, Li Y, Hatzoglou M, Previs S. Preserved protein synthesis in the heart in response to acute fasting and chronic food restriction despite reductions in liver and skeletal muscle. Am J Physiol (Endocrinol Metab). 295:E216-222, 2008.
Rosca MG, Vazquez EJ, Kerner J, Parland W, Chandler MP, Stanley W, Sabbah HN, Hoppel CL. Cardiac mitochondria in heart failure: decrease in respirasomes and oxidative phosphorylation. Cardiovasc Res 80:30-39, 2008
Lei B, Chess DJ, Keung W, O'Shea KM, Lopaschuk GD, Stanley WC. Transient activation of P38 MAP kinase and up-regulation of Pim-1kinase in cardiac hypertrophy despite no activation of AMPK, J Mol Cell Cardiol 45:404-10, 2008.
Lu M, Zhou L, Stanley WC, Cabrera ME, Saidel GM, Yu X. Localization of malate-aspartate shuttle and metabolic communication during myocardial ischemia. J. Theoretical Biology 254:466-475, 2008
Zhou L, Huang H, McElfresh TA, Prosdocimo A, Stanley WC. Impact of anaerobic glycolysis and oxidative substrate selection on contractile function and mechanical efficiency during moderate severity ischemia. Am J Physiol 295:H939-945, 2008.
Zungu M, Young ME, Stanley WC, Essop MF. Expression of mitochondrial regulatory genes parallels respiratory capacity and contractile function in a rat model of hypoxia-induced right ventricular hypertrophy. Mol Cell Biochem. 318:175-81, 2008.
Qanud K, Mamdani M, Pepe M, Gravel J, Gupte SA, Khairallah RJ, Sharov V, Sabbah HN, Stanley WC, Recchia FA. Reverse remodeling of cardiac metabolic phenotype in dogs recovering from pacing-induced heart failure. Am J Physiol Heart Circ Physiol 295:2098-2105, 2008.
Rastogi S, Sharov VG, Mishra S, Gupta RC, Blackburn B,Belardinelli L, Stanley WC, Sabbah HN. Long-term therapy with the antianginal drug ranolazine prevents progressive left ventricular dysfunction and remodeling in dogs with heart failure. Am J Physiol Heart Circ Physiol 295: H2149-H2155, 2008.
Chess DJ, Xu W, Khairallah R, O'Shea, KM, Azimzadeh AM, Stanley WC. The antioxidant tempol attenuates pressure overload-induced cardiac hypertrophy and contractile dysfunction in mice fed a high-fructose diet. Am J Physiol (Heart Circ Physiol) 295: H2223â?"H2230, 2008.
Duda MK, O'Shea KM, Tintinu A, Xu W, Khairallah RJ, Barrows BR, Chess DJ, Azimzadeh AM, Harris, WS, Sharov VG, Sabbah HN, Stanley WC. Dietary supplementation with fish oil, but not flaxseed oil, elevates adiponectin, decreases inflammation, and prevents pressure overload induced ventricular remodeling and dysfunction. Cardiovasc Res 81, 319-327, 2009 .
Rosca MG, Okere IC, Sharma N, Stanley WC, Recchia FA, Charles L. Hoppel. Altered expression of the adenine nucleotide translocase isoforms and decreased ATP synthase activity in skeletal muscle mitochondria in heart failure. J Molec Cell Cardiol 46:927-935, 2009.
Zungu M, Young ME, Stanley WC, Essop MF. Chronic Treatment with the peroxisome proliferator-activated receptor Î± agonist WY-14,643 attenuates myocardial respiratory capacity and contractile function. Molec Cell Biochem (in press).
Shah KB, Duda MK, O'Shea KM, Sparagna GC, Chess DJ, Khairallah RJ, Frayne-Robillard I, Xu W, Murphy RC. Des Rosiers R, Stanley WC. The cardioprotective effects of fish oil during pressure overload are blocked by high fat intake: role of cardiac phospholipid remodeling. Hypertension, 2009 (in press)
Duda MK, O'Shea KM, Stanley WC. Omega-3 Polyunsaturated fatty acid supplementation for the treatment of heart failure: mechanisms and clinical potential. Cardiovasc Res 2009 (in press).