Kerry S Russell MD/PhD, FACC, FAHA
Associate Professor of Medicine (Cardiology)
Research Interests
Signaling pathways in vascular function and heart failure
Research Summary
Dr. Kerry Russell studies signaling pathways induced by growth factors of the neuregulin family, and their erbB receptors, and the effect of activation on vascular form and function.
Extensive Research Description
Our research broadly encompasses 2 common themes in cardiovascular medicine: preservation of cardiac function and promotion of angiogenesis. We have chosen to focus on 2 major targets in the cardiovascular system that could potentially be manipulated to achieve the goals of myocyte preservation and angiogenesis. The first of these targets is the neuregulin/erbB ligand/receptor system. Evidence for the importance of this signaling system in the heart comes from clinical data showing that interruption of this system (e.g. using Herceptin in breast cancer patients) leads to depression of cardiac function, ultimately leading to heart failure in some patients. Our work over the past years has shown that activation of this signaling system can protect cardiac myocytes against injury in response to ischemia and can promote angiogenesis. The second target under investigation is the IL-6/STAT3 signaling cascade. Clinical data has revealed a paradoxical relationship between detrimental and protective effects of several “pro-inflammatory” cytokine pathways, including that of IL-6, in patients with heart failure. Our data suggests that one particular downstream target of IL-6 signaling, the STAT3 protein, may be important for the cardioprotective effects of IL-6. We hope that unraveling the details of this signaling pathway will provide novel targets to protect the heart in the setting of ischemic or inflammatory injury.
Selected Publications
- Kalinowski, A, Plowes, NJ, Huang, Q, Berdejo-Izquierdo, C, Russell, RR, and Russell, KS. Metalloproteinase-dependent cleavage of neuregulin and autocrine stimulation of vascular endothelial cells. FASEB J. 2010; 24, 2567-2575.
- Parks, J, Fong , PM, Lu, J, Russell, KS, Booth, CJ, Saltzman, MW, Fahmy TM. PEGylated PLGA nanoparticles for the improved delivery of doxorubicin. Nanomedicine. 2009; 5:410-418.
- Wendler, CC, Busovsky-McNeal, M, Ghatpande, S, Kalinowski, A., Russell, KS, Rivkees, SA. Embryonic caffeine exposure induces adverse effects in adulthood. FASEB J. 2009;23:1272-1278.
- Park SY, Cho YR, Kim HJ, Higashimori T, Danton C, Lee MK, Dey A, Rothermel B, Kim YB, Kalinowski A, Russell KS, Kim JK. Unraveling the temporal pattern of diet-induced insulin resistance in individual organs and cardiac dysfunction in C57BL/6 mice. Diabetes. 2005 54(12):3530-3540.
- Park SY, Cho YR, Finck BN, Kim HJ, Higashimori T, Hong EG, Lee MK, Danton C, Deshmukh S, Cline GW, Wu JJ, Bennett AM, Rothermel B, Kalinowski A, Russell KS, Kim YB, Kelly DP, Kim JK. Cardiac-specific overexpression of peroxisome proliferator-activated receptor-{alpha} causes insulin resistance in heart and liver. Diabetes. 2005 54(9):2514-2524.
- Jacoby JJ, Kalinowski A, Liu MG, Zhang SS, Gao Q, Chai GX, Ji L, Iwamoto Y, Li E, Schneider M, Russell KS, Fu XY. Cardiomyocyte-restricted knockout of STAT3 results in higher sensitivity to inflammation, cardiac fibrosis, and heart failure with advanced age. Proc Natl Acad Sci U S A. 2003 100(22):12929-12934.
- Haynes MP, Li L, Sinha D, Russell KS, Hisamoto K, Baron R, Collinge M, Sessa WC, Bender JR. Src kinase mediates phosphatidylinositol 3-kinase/Akt-dependent rapid endothelial nitric-oxide synthase activation by estrogen. J Biol Chem. 2003 278(4):2118-2123.
- Haynes MP, Li L, Russell KS, Bender JR. Rapid vascular cell responses to estrogen and membrane receptors. Vascul Pharmacol. 2002 38(2):99-108.
- Russell KS, Haynes MP, Sinha D, Clerisme E, Bender JR. Human vascular endothelial cells contain membrane binding sites for estradiol, which mediate rapid intracellular signaling. Proc Natl Acad Sci U S A. 2000 97:5930-5.
- Russell KS, Haynes MP, Caulin-Glaser T, Rosneck J, Sessa WC, Bender JR. Estrogen stimulates heat shock protein 90 binding to endothelial nitric oxide synthase in human vascular endothelial cells. Effects on calcium sensitivity and NO release. J Biol Chem. 2000 275:5026-30.
Selected Publications
- Kalinowski, A, Plowes, NJ, Huang, Q, Berdejo-Izquierdo, C, Russell, RR, and Russell, KS. Metalloproteinase-dependent cleavage of neuregulin and autocrine stimulation of vascular endothelial cells. FASEB J. 2010; 24, 2567-2575.
- Parks, J, Fong , PM, Lu, J, Russell, KS, Booth, CJ, Saltzman, MW, Fahmy TM. PEGylated PLGA nanoparticles for the improved delivery of doxorubicin. Nanomedicine. 2009; 5:410-418.
- Wendler, CC, Busovsky-McNeal, M, Ghatpande, S, Kalinowski, A., Russell, KS, Rivkees, SA. Embryonic caffeine exposure induces adverse effects in adulthood. FASEB J. 2009;23:1272-1278.
- Park SY, Cho YR, Kim HJ, Higashimori T, Danton C, Lee MK, Dey A, Rothermel B, Kim YB, Kalinowski A, Russell KS, Kim JK. Unraveling the temporal pattern of diet-induced insulin resistance in individual organs and cardiac dysfunction in C57BL/6 mice. Diabetes. 2005 54(12):3530-3540.
- Park SY, Cho YR, Finck BN, Kim HJ, Higashimori T, Hong EG, Lee MK, Danton C, Deshmukh S, Cline GW, Wu JJ, Bennett AM, Rothermel B, Kalinowski A, Russell KS, Kim YB, Kelly DP, Kim JK. Cardiac-specific overexpression of peroxisome proliferator-activated receptor-{alpha} causes insulin resistance in heart and liver. Diabetes. 2005 54(9):2514-2524.
- Jacoby JJ, Kalinowski A, Liu MG, Zhang SS, Gao Q, Chai GX, Ji L, Iwamoto Y, Li E, Schneider M, Russell KS, Fu XY. Cardiomyocyte-restricted knockout of STAT3 results in higher sensitivity to inflammation, cardiac fibrosis, and heart failure with advanced age. Proc Natl Acad Sci U S A. 2003 100(22):12929-12934.
- Haynes MP, Li L, Sinha D, Russell KS, Hisamoto K, Baron R, Collinge M, Sessa WC, Bender JR. Src kinase mediates phosphatidylinositol 3-kinase/Akt-dependent rapid endothelial nitric-oxide synthase activation by estrogen. J Biol Chem. 2003 278(4):2118-2123.
- Haynes MP, Li L, Russell KS, Bender JR. Rapid vascular cell responses to estrogen and membrane receptors. Vascul Pharmacol. 2002 38(2):99-108.
- Russell KS, Haynes MP, Sinha D, Clerisme E, Bender JR. Human vascular endothelial cells contain membrane binding sites for estradiol, which mediate rapid intracellular signaling. Proc Natl Acad Sci U S A. 2000 97:5930-5.
- Russell KS, Haynes MP, Caulin-Glaser T, Rosneck J, Sessa WC, Bender JR. Estrogen stimulates heat shock protein 90 binding to endothelial nitric oxide synthase in human vascular endothelial cells. Effects on calcium sensitivity and NO release. J Biol Chem. 2000 275:5026-30.
- Russell KS, Stern DF, Polverini PJ, Bender JR. Neuregulin activation of ErbB receptors in vascular endothelium leads to angiogenesis. Am J Physiol. 1999 277:H2205-11
