Karen O’Shea, PhD, Postdoctoral Fellow
I received my PhD in Nutritional Biochemistry and Metabolism from Case Western Reserve University where I focused on the impact of omega-3 polyunsaturated fatty acids in heart failure.
I currently work as a postdoctoral fellow with the Diabetes Research Group to investigate the mechanisms of the increased susceptibility of the heart to ischemia/reperfusion injury in diabetes. Previous studies by our laboratory have revealed a central role for the receptor for advanced glycation end-products (RAGE) in ischemia/reperfusion by contributing to subsequent oxidative stress and mitochondrial dysfunction. The RAGE cytoplasmic domain interacts with diaphanous-1 (mDia-1), a member of the formin family, and an effector of Rho GTPases.
The goal of my research is to investigate underlying signaling mechanisms in cardiomyocytes involving RAGE and mDia-1 in response to ischemia/reperfusion injury.
1. Papanicolaou KN, Khairallah RJ, Ngoh G, Chikando A, Luptak I, O’Shea KM, Riley DD, Lugus JJ, Colucci WS, Lederer WJ, Stanley WC, and Walsh K. Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes. Mol Cell Biol 2011 31:1309-28.
2. Hecker PA, O’Shea KM, Galvao TF, Brown BH, and Stanley WC. Role of adiponectin in the development of high-fat diet-induced metabolic abnormalities in mice. Horm Metab Res 2011 43:100-5.
3. O'Shea KM, Chess DJ, Khairallah RJ, Hecker P, Lei B, Walsh K, Des Rosiers C, and Stanley WC. ω-3 polyunsaturated fatty acids prevent pressure overload-induced ventricular dilation and decrease in mitochondrial enzymes despite no change in adiponectin. Lipids Health Dis 2010 9:95.
4. Khairallah RJ, O’Shea KM, Brown BH, Khanna N, Des Rosiers C, and Stanley WC. Treatment with docosahexaenoic acid, but not eicosapentaenoic acid, delays Ca2+-induced mitochondrial permeability transition in normal and hypertrophied myocardium. J Pharmacol Exp Ther 2010 335:155-162.
5. Khairallah RJ, Sparagna GC, Khanna N, O’Shea KM, Hecker PA, Des Rosiers C, Fiskum G, and Stanley WC. Dietary supplementation with docosahexaenoic acid, but not eicosapentanoic acid, profoundly remodels cardiac mitochondrial phospholipid fatty acid composition and prevents permeability transition. Biochim Biophys Acta 2010 1797:1555-1562.
6. O’Shea KM, Chess DJ, Khairallah RJ, Rastogi S, Hecker PA, Sabbah HN, Walsh K, and Stanley WC. Adiponectin plays a permissive role for structural and metabolic remodeling in mice subjected to pressure overload. Am J Physiol Heart Circ Physiol 2010 298:H1639-45.
7. Chess DJ, Khairallah RJ, O’Shea KM, Xu W, and Stanley WC. Dietary fat-induced adiposity elevates leptin, prevents down regulation of mitochondrial oxidative enzymes, and does not worsen cardiac dysfunction in response to pressure overload. Am J Physiol Heart Circ Physiol 2009 297:H1585-93.
8. O’Shea KM, Khairallah RJ, Sparagna GC, Xu W, Hecker PA, Robillard-Frayne I, Des Rosiers C, Kristian T, Murphy RC, Fiskum G, and Stanley WC. Dietary ω-3 fatty acids alter cardiac mitochondrial phospholipid composition and delay Ca2+-induced permeability transition. J Mol Cell Cardiol 2009 47:819-27.
9. Shah KB, Duda MK, O’Shea KM, Sparagna GC, Chess DJ, Khairallah RJ, Frayne-Robillard I, Xu W, Murphy RC, Des Rosiers C, and Stanley WC. High fat intake alters cardiac phospholipid composition and prevents cardioprotection with fish oil during pressure overload. Hypertension 2009 54:605-11.
10. Duda MK, O’Shea KM, and Stanley WC. Omega-3 polyunsaturated fatty acid supplementation for the treatment of heart failure: mechanisms and clinical potential. Cardiovasc Res 2009 84:33-41.
11. Duda MK, O'Shea KM, Tintinu A, Xu W, Khairallah RJ, Barrows BR, Chess DJ, Azimzadeh AM, Harris WS, Sharov VG, Sabbah HN, and Stanley WC. Fish oil, but not flaxseed oil, decreases inflammation and prevents pressure overload-induced cardiac dysfunction. Cardiovasc Res 2009 81:319-27.
12. Chess DJ, Xu W, Khairallah R, O'Shea KM, Kop WJ, Azimzadeh AM, and 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 2008 295:H2223-30.
13. Lei B, Chess DJ, Keung W, O'Shea KM, Lopaschuk GD, and Stanley WC. Transient activation of p38 MAP kinase and up-regulation of Pim-1 kinase in cardiac hypertrophy despite no activation of AMPK. J Mol Cell Cardiol 2008 45:404-10.
14. Duda MK, O’Shea KM, Lei B, Barrows BR, Azimzadeh A, McElfresh TE, Hoit BD, Kop WJ, and Stanley WC. Low carbohydrate/high fat diet attenuates pressure overload induced ventricular remodeling and dysfunction. J Card Fail 2008; 14:327-35.
15. Duda MK, O'Shea KM, Barrows BR, Lei B, Azimzadeh A, McElfresh TE, Hoit BD, and Stanley WC. Dietary supplementation with ω-3 polyunsaturated fatty acids increases plasma adiponectin and prevents ventricular remodeling and dysfunction with pressure overload. Cardiovasc Res 2007;76:303-310.
16. King KL, Young ME, Kerner J, Huang H, O’Shea KM, Alexson SEH, Hoppel CL, and Stanley WC. Diabetes and activation of peroxisome proliferator activated receptor α selectively up-regulate mitochondrial thioesterase I activity and protein expression in the heart. J Lipid Res 2007;48:1511-1517.
17. Sharma N, Okere IC, Duda MK, Chess DJ, O'Shea KM, and Stanley WC. Potential impact of carbohydrate and fat intake on pathological left ventricular hypertrophy. Cardiovasc Res 2007;73:257-268.