Alex F. Chen, Ph.D.
Associate Professor, Pharmacology, Neurology, Cell and Molecular Biology, Neuroscience Program

Academic Appointments

Research Synopsis

The long-term research interest of our laboratory is in the areas of vascular biology, pharmacology, and gene and cell therapies.  Our current objective, which is a step toward attaining our long-term goal, is to determine the effects of gene and cell therapies on vascular functions in diseased animal models.  The disease targets include diabetic and hypertensive vascular dysfunction, impaired diabetic wound healing, and ischemic stroke.  Our ultimate goal is to translate basic research to clinical arena for gene and cell therapies of cardiovascular and cerebrovascular diseases.

Comprehensive approaches are utilized to study transgene expression and its effects, including molecular, biochemical, morphological, and pharmacological techniques.  The methods include adenoviral vector propagation, ex vivo and in vivo gene transfer, immunohistochemistry, radioimmunoassay, immunoblotting, isometric tension recordings, and the use of both transgenic and gene knockout animals.

Current Projects:

• The molecular mechanisms of endothelial progenitor cell dysfunction in diabetes and hypertension (supported by NIH R01).
• Oxidative stress mechanisms and endothelial dysfunction in hypertension (supported by NIH P01).
• BH4 regulation of cerebrovascular injury (e.g. restenosis) (supported by the American Heart Association).
• The effects of gene transfer of antioxidant enzymes (e.g. superoxide dismutase) on endothelial progenitor cell function and angiogenesis (supported by the American Diabetes Association).

Selected Achievements since 2001:

• 2/2001 – Present Executive Committee, Division for Systems and Integrative Pharmacology, American Society of Pharmacology and Experimental Therapeutics (ASPET)
• 1/2002 – 4/2005 Member, AHA National Brain and Stroke 2 Peer Review Study Section
• 2/1998 – Present Fellow, AHA Stroke Council
• 9/2002 – Present Fellow, AHA Council for High Blood Pressure Research
• 7/2004 – Present Executive Committee Member, Division of Cardiovascular Pharmacology, American Society of Pharmacology and Experimental Therapeutics (ASPET)
• 1/2005 – Present North American Editor, Acta Pharmacologica Sinica
• 6/2005 – Present Editorial board member, Journal of Cardiothoracic and Renal Research
• 10/2005 – Present Editorial board member, Atherosclerosis, Thrombosis and Vascular Biology
• 2/2006 – Present National Merit Review Panel, Veterans Health Administration, US Department of Veterans Affairs
• 1/2007 – Present Editorial board member, American Journal of Physiology (Heart & Circ Physiology)
• 2/2007 – Present Editor for Diabetes and Obesity/Metabolic, Clinical and Experimental Pharmacology and Physiology
• 2/2007 – Present Member, AHA National Vascular Biology Blood Pressure/Regulation 2 Study Section
• 6/2007 – Present Member, American Diabetes Association (ADA) National Study Section

Selected Samples of Publications

1. Chen, FY, Lee, TJ-F. Role of nitric oxide in neurogenic vasodilation of porcine cerebral artery. Journal of Pharmacology and Experimental Therapeutics 265: 339-345, 1993
2. Chen, FY, Lee, TJ-F. Arginine synthesis from citrulline in perivascular nerves of cerebral artery. Journal of Pharmacology and Experimental Therapeutics 273: 895-901, 1995
3. Chen AF, Jiang S, Crotty TB, Tsutsui M, Smith LA, O’Brien T, Katusic ZS. Effects of in vivo adventitial expression of recombinant endothelial nitric oxide synthase gene in cerebral arteries. Proceedings of National Academy of Science of USA 94, 12568-12573, 1997
4. Chen AF, O’Brien T, Tsutsui M, Kinoshita H, Pompili VJ, Crotty TB, Spector DJ, Katusic ZS. Expression and function of recombinant endothelial nitric oxide synthase gene in canine basilar artery. Circulation Research 80, 327-335, 1997
5. Chen AFY, O’Brien T, Katusic ZS. Transfer and expression of recombinant nitric oxide synthase genes in cardiovascular system. Trends in Pharmacologic Sciences 19, 276-286, 1998
6. Li L, Crockett E, Wang DH, Galligan JJ, Fink GD, Chen AF. Gene transfer of endothelial NO synthase and manganese superoxide dismutase on arterial vascular cell adhesion molecule-1 expression and superoxide production in deoxycorticosterone acetate-salt hypertension. Arteriosclerosis Thrombosis and Vascular Biology 22: 249-255, 2002
7. Li L, Fink GD, Watts SW, Galligan JJ, Pagano PJ, Chen AF. Endothelin-2 increases vascular superoxide via ETA-NADPH oxidase pathway in low renin hypertension. Circulation 107, 1053-1058, 2003.
8. Li LX, Galligan JJ, Fink GD, Chen AF: Vasopressin enhances vascular superoxide production by activating endothelin-1 in mineralocorticoid hypertension. Hypertension 41, 663-668, 2003
9. Zheng JS, Yang XQ, Lookingland KJ, Fink GD, Hesslinger C, Kapatos G, Kovesdi I, Chen AF: Gene transfer of human guanosine 5’-triphosphate cyclohydrolase I restores vascular tetrahydrobiopterin level and endothelial function in mineralocorticoid hypertension. Circulation 108, 1238-1245, 2003
10. Li LX, Watts SW, Banes AK, Galligan JJ, Fink GD, Chen AF: NADPH oxidase-derived superoxide augments endothelin-1-induced venoconstriction in mineralocorticoid hypertension. Hypertension 42, 316-321, 2003
11. Li L, Chu Y, Fink GD, Engelhardt JF, Heistad DD, Chen AF: Endothelin-1 stimulates arterial VCAM-1 expression via NADPH oxidase-derived superoxide in mineralocorticoid hypertension. Hypertension 42, 997-1003, 2003
12. Ren J, Zhang X, Scott GI, Esberg LB, Ren BH, Culver B, Chen AF. Adenovirus gene transfer of recombinant endothelial nitric oxide synthase enhances contractile function in ventricular myocytes. Journal of Cardiovascular Pharmacology 43, 171-177, 2004
13. Xu FP, Chen MS, Wang YZ, Yi Q, Lin SB, Chen AF, Luo JD: Leptin induces hypertrophy via endothelin-1-reactive oxygen species pathway in cultured neonatal rat cardiomyocytes. Circulation 110, 1269-1275, 2004
14. Luo JD, Wang YY, Fu WL, Wu J, Chen AF: Gene therapy of endothelial nitric oxide synthase and manganese superoxide dismutase restores delayed wound healing in Type I diabetic mice. Circulation 110, 2484-2493, 2004
15. Zheng JS, Tang LL, Zheng SS, Zhan RY, Zhou YQ, Chen AF. Gene therapy of glial cell line-derived neurotrophic factor in a rat model of late stage Parkinson’s disease. Molecular Brain Research 134, 155-161, 2005
16. Kidd, GA, Hong H, Majid A, Kaufman DI, Chen AF. Inhibition of brain GTP cyclohydrolase I and tetrahydrobiopterin attenuates cerebral infarction via reducing iNOS and peroxynitrite in ischemic stroke. Stroke 36, 2705-2711, 2005
17. Hong H. Zeng JS, Kreleun DL, Kaufman DI, Chen AF. Atorvastatin protects against cerebral infarction via inhibiting NADPH oxidase-derived superoxide in ischemic stroke. American Journal of Physiology (Heart and Circulatory Physiology) 291, H2210-H2215, 2006
18. Chen DD, Chen AF. CuZn-SOD deficiency: a culprit of accelerated vascular aging process. (Invited Editorial Commentary) Hypertension 48, 1026-1028, 2006
19. Du YH, Chen AF. A “love triangle” elicited by electrochemistry amongst brain, heart and kidney – complex interactions between cardiac sympathetic afferent and chemoreceptor reflexes. (Invited Editorial) Journal of Applied Physiology 102, 9-10, 2007
20. Liao SJ, Lin L, Zeng JS, Fink GD, Galligan JJ, Chen AF. Endothelial-targeted GTP cyclohydrolase I overexpression inhibits restenosis in mouse carotid artery, Clinical and Experimental Pharmacology and Physiology, 2007, In Press

Postdoctoral Training

• 1999: NIH Postdoctoral Fellow in Anesthesia Research, Mayo Clinic

Education

• Ph.D., Pharmacology, Southern Illinois University, 1995
• B.S., Hunan Medical University, Medicine, 1985

Research Webpages

• http://www.phmtox.msu.edu/faculty/chen.php
• http://www.ns.msu.edu/neurosci/people/faculty/chen.htm