Zheng-Gen Jin
| Title | Associate Professor |
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| Institution | School of Medicine and Dentistry |
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| Department | Medicine in the Aab Cardiovascular Research Institute |
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| Address | Aab Cardiovascular Research Institute
211 Bailey Road
West Henrietta NY 14586
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Research
* Molecular regulation of vascular endothelial function.
Dr. Jin's research has been focused on molecular regulation of vascular endothelial function. Vascular endothelial cells in blood vessels produce a number of vasodilator and vasoconstrictor substances that not only physiologically regulate vasomotor tone and vascular homeostasis, but also mediate the recruitment and activity of inflammatory cells and the propensity towards atherosclerotic lesion formation and thrombosis in the pathological condition. Normal laminar shear stress, a fractional force generated by blood flow, regulates the activity of endothelial nitric oxide synthase (eNOS) and promotes the expression of genes in endothelial cells that may protect against atherosclerosis. In contrast, oxidant stress caused by over-production of reactive oxygen species plays a major role in impairing vascular functions, by reducing the bioavailability of nitric oxide and stimulating proinflammatory pathways. By understanding the nature of molecular regulation of endothelial function and dysfunction by shear stress and oxidative stress as well as growth factors and cytokines, Dr. Jin's research will help to develop novel therapeutic strategies for preventing atherosclerotic vascular diseases.
The specific ongoing projects in the lab are: 1) to characterize the signaling pathways involved in flow-mediated eNOS activation and anti-inflammatory effect; 2) to identify specific intracellular signaling molecules essential for oxidative stress-induced endothelial dysfunction; 3) to define the molecular mechanisms of endothelial proinflammatory and angiogenetic responses to growth factors and cytokines.
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Jhun BS, O-Uchi J, Wang W, Ha CH, Zhao J, Kim JY, Wong C, Dirksen RT, Lopes CM, Jin ZG. Adrenergic Signaling Controls RGK-Dependent Trafficking of Cardiac Voltage-Gated L-Type Ca2+ Channels Through PKD1. Circ Res. 2012 Jan 6; 110(1):59-70.
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Zhao J, Wang W, Ha CH, Kim JY, Wong C, Redmond EM, Hamik A, Jain MK, Feng GS, Jin ZG. Endothelial Grb2-associated binder 1 is crucial for postnatal angiogenesis. Arterioscler Thromb Vasc Biol. 2011 May; 31(5):1016-23.
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Ha CH, Kim JY, Zhao J, Wang W, Jhun BS, Wong C, Jin ZG. PKA phosphorylates histone deacetylase 5 and prevents its nuclear export, leading to the inhibition of gene transcription and cardiomyocyte hypertrophy. Proc Natl Acad Sci U S A. 2010 Aug 31; 107(35):15467-72.
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Edirisinghe I, Arunachalam G, Wong C, Yao H, Rahman A, Phipps RP, Jin ZG, Rahman I. Cigarette-smoke-induced oxidative/nitrosative stress impairs VEGF- and fluid-shear-stress-mediated signaling in endothelial cells. Antioxid Redox Signal. 2010 Jun 15; 12(12):1355-69.
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Wang W, Ha CH, Jhun BS, Wong C, Jain MK, Jin ZG. Fluid shear stress stimulates phosphorylation-dependent nuclear export of HDAC5 and mediates expression of KLF2 and eNOS. Blood. 2010 Apr 8; 115(14):2971-9.
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Ha CH, Jin ZG. Protein kinase D1, a new molecular player in VEGF signaling and angiogenesis. Mol Cells. 2009 Jul 31; 28(1):1-5.
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Ha CH, Jhun BS, Kao HY, Jin ZG. VEGF stimulates HDAC7 phosphorylation and cytoplasmic accumulation modulating matrix metalloproteinase expression and angiogenesis. Arterioscler Thromb Vasc Biol. 2008 Oct; 28(10):1782-8.
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Satoh K, Matoba T, Suzuki J, O'Dell MR, Nigro P, Cui Z, Mohan A, Pan S, Li L, Jin ZG, Yan C, Abe J, Berk BC. Cyclophilin A mediates vascular remodeling by promoting inflammation and vascular smooth muscle cell proliferation. Circulation. 2008 Jun 17; 117(24):3088-98.
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Xu X, Jhun BS, Ha CH, Jin ZG. Molecular mechanisms of ghrelin-mediated endothelial nitric oxide synthase activation. Endocrinology. 2008 Aug; 149(8):4183-92.
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Zhang Q, Guo R, Lu Y, Zhao L, Zhou Q, Schwarz EM, Huang J, Chen D, Jin ZG, Boyce BF, Xing L. VEGF-C, a lymphatic growth factor, is a RANKL target gene in osteoclasts that enhances osteoclastic bone resorption through an autocrine mechanism. J Biol Chem. 2008 May 9; 283(19):13491-9.
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Ha CH, Wang W, Jhun BS, Wong C, Hausser A, Pfizenmaier K, McKinsey TA, Olson EN, Jin ZG. Protein kinase D-dependent phosphorylation and nuclear export of histone deacetylase 5 mediates vascular endothelial growth factor-induced gene expression and angiogenesis. J Biol Chem. 2008 May 23; 283(21):14590-9.
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Edirisinghe I, Yang SR, Yao H, Rajendrasozhan S, Caito S, Adenuga D, Wong C, Rahman A, Phipps RP, Jin ZG, Rahman I. VEGFR-2 inhibition augments cigarette smoke-induced oxidative stress and inflammatory responses leading to endothelial dysfunction. FASEB J. 2008 Jul; 22(7):2297-310.
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Ha CH, Bennett AM, Jin ZG. A novel role of vascular endothelial cadherin in modulating c-Src activation and downstream signaling of vascular endothelial growth factor. J Biol Chem. 2008 Mar 14; 283(11):7261-70.
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Xu X, Ha CH, Wong C, Wang W, Hausser A, Pfizenmaier K, Olson EN, McKinsey TA, Jin ZG. Angiotensin II stimulates protein kinase D-dependent histone deacetylase 5 phosphorylation and nuclear export leading to vascular smooth muscle cell hypertrophy. Arterioscler Thromb Vasc Biol. 2007 Nov; 27(11):2355-62.
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Suzuki J, Jin ZG, Meoli DF, Matoba T, Berk BC. Cyclophilin A is secreted by a vesicular pathway in vascular smooth muscle cells. Circ Res. 2006 Mar 31; 98(6):811-7.
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Wong C, Jin ZG. Protein kinase C-dependent protein kinase D activation modulates ERK signal pathway and endothelial cell proliferation by vascular endothelial growth factor. J Biol Chem. 2005 Sep 30; 280(39):33262-9.
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Tai LK, Zheng Q, Pan S, Jin ZG, Berk BC. Flow activates ERK1/2 and endothelial nitric oxide synthase via a pathway involving PECAM1, SHP2, and Tie2. J Biol Chem. 2005 Aug 19; 280(33):29620-4.
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Jin ZG, Wong C, Wu J, Berk BC. Flow shear stress stimulates Gab1 tyrosine phosphorylation to mediate protein kinase B and endothelial nitric-oxide synthase activation in endothelial cells. J Biol Chem. 2005 Apr 1; 280(13):12305-9.
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Jin ZG, Berk BC. Role of secreted oxidative stress-induced factors (SOXFs) in the pathogenesis of atherosclerosis. Arch Mal Coeur Vaiss. 2004 Dec; 97(12):1256-9.
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Narins CR, Lin DA, Burton PB, Jin ZG, Berk BC. Interleukin-18 and interleukin-18 binding protein levels before and after percutaneous coronary intervention in patients with and without recent myocardial infarction. Am J Cardiol. 2004 Nov 15; 94(10):1285-7.
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Melaragno MG, Cavet ME, Yan C, Tai LK, Jin ZG, Haendeler J, Berk BC. Gas6 inhibits apoptosis in vascular smooth muscle: role of Axl kinase and Akt. J Mol Cell Cardiol. 2004 Oct; 37(4):881-7.
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Lungu AO, Jin ZG, Yamawaki H, Tanimoto T, Wong C, Berk BC. Cyclosporin A inhibits flow-mediated activation of endothelial nitric-oxide synthase by altering cholesterol content in caveolae. J Biol Chem. 2004 Nov 19; 279(47):48794-800.
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Jin ZG, Lungu AO, Xie L, Wang M, Wong C, Berk BC. Cyclophilin A is a proinflammatory cytokine that activates endothelial cells. Arterioscler Thromb Vasc Biol. 2004 Jul; 24(7):1186-91.
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Jin ZG, Berk BC. SOXF: redox mediators of vascular smooth muscle cell growth. Heart. 2004 May; 90(5):488-90.
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Jin ZG, Ueba H, Tanimoto T, Lungu AO, Frame MD, Berk BC. Ligand-independent activation of vascular endothelial growth factor receptor 2 by fluid shear stress regulates activation of endothelial nitric oxide synthase. Circ Res. 2003 Aug 22; 93(4):354-63.
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Tanimoto T, Jin ZG, Berk BC. Transactivation of vascular endothelial growth factor (VEGF) receptor Flk-1/KDR is involved in sphingosine 1-phosphate-stimulated phosphorylation of Akt and endothelial nitric-oxide synthase (eNOS). J Biol Chem. 2002 Nov 8; 277(45):42997-3001.
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Jin ZG, Melaragno MG, Liao DF, Yan C, Haendeler J, Suh YA, Lambeth JD, Berk BC. Cyclophilin A is a secreted growth factor induced by oxidative stress. Circ Res. 2000 Oct 27; 87(9):789-96.
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Liao DF, Jin ZG, Baas AS, Daum G, Gygi SP, Aebersold R, Berk BC. Purification and identification of secreted oxidative stress-induced factors from vascular smooth muscle cells. J Biol Chem. 2000 Jan 7; 275(1):189-96.
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