Dr. Xuan

by c0li0003 — last modified Apr 08, 2009 02:57 PM

Yu-Ting Xuan, Ph.D.

Professor of Medicine

Tel.: (502) 852-8428

E-mail: ytxuan01@louisville.edu

Dr. Xuan received a Ph.D. at Duke University. He has extensive experience in cellular biology, signal transduction, and particularly in the role of the cardioprotective proteins in myocardial injuries. Dr. Xuan' research has been focused on understanding of the signaling mechanisms and the transcriptional regulation of the expression of cardioprotective genes and proteins that underlie myocardial pathophysiology associated with cardiac diseases. Research studies are aimed at (i) identifying the early signaling events following ischemic preconditioning, (ii) identifying the cytosolic transcription factors important for cardioprotection, and (iii) characterizing the role of cardioprotctive proteins in preconditioning in both a conscious rabbit model and an open-chest mouse model of late PC.

Previous works had shown the triggering role of eNOS activation in late PC, the essential role of transcription factors such as nuclear factor- kB (NF-kB) and signal transducers and activators of transcription (STATs) in the transcriptional activation of the iNOS gene and in the development of late PC, and the necessary role of the upregulated iNOS and cyclooxygenase-2 (COX-2) by brief ischemic insults in the cardioprotective effects of late PC against myocardial infarction. Dr. Xuan has carefully examined the roles of iNOS and cNOS in late PC by measuring changes in iNOS and cNOS protein levels and activity, nitrate and nitrite production, and changes in myocardial protection. Recent results demonstrate that NOS plays a key role in the cardioprotection afforded by late PC, with cNOS acting initially as the trigger and iNOS acting subsequently as the mediator. Current research is directed toward investigating the transcription factors and signaling pathways involved in the transcriptional regulation of the iNOS, COX-2, and other cardioprotective genes during late PC. The long-range goal of Dr. Xuan’s research is to elucidate the cellular and molecular mechanisms that underlie the late phase of ischemic preconditioning and pharmacological preconditioning.

Selected Publication:

1. Hamid T, Gu Y, Ortines RV, Bhattacharya C, Wang G, Xuan YT, Prabhu SD. Diver Divergent Tumor Necrosis Factor Receptor–Related Remodeling Responses in Heart Failure Role of Nuclear Factor-kB and Inflammatory Activation. Circulation. 119:1386-1397, 2009.
2. West MB, Rokosh G, Obal D, Velayutham M, Xuan YT, Hill BG, Keith RJ, Schrader J, Guo Y, Conklin DJ, Prabhu SD, Zweier JL, Bolli R, Bhatnagar A. Cardiac myocyte-specific expression of inducible nitric oxide synthase protects against ischemia/reperfusion injury by preventing mitochondrial permeability transition. Circulation. 118:1970-8, 2008.
3. Xuan YT, Guo Y, Zhu Y, Wang OL, Rokosh G, Bolli R. Endothelial nitric oxide synthase plays an obligatory role in the late phase of ischemic preconditioning by activating the protein kinase C{epsilon}-p44/42 mitogen-activated protein kinase-pSer-signal transducers and activators of transcription1/3 pathway. Circulation. 2007 Jul 31;116(5):535-44.
4. Stein AB, Bolli R, Guo Y, Wang OL, Tan W, Wu WJ, Zhu XP, Zhu Y, Xuan YT. The late phase of ischemic preconditioning induces a prosurvival genetic program that results in marked attenuation of apoptosis. J Mol Cell Cardiol. 42:1075-1085, 2007.
5. West MB, Hill BG, Xuan YT, Bhatnagar A. Protein glutathiolation by nitric oxide: An intracellular mechanism regulating redox protein modification. FASEB J. 20(10):E1049-E1060, 2006.
6. Luo J, Xuan YT, Gu Y, Prabhu SD. Prolonged oxidative stress inverts the cardiac force-frequency relation: role of altered calcium handling and myofilament calcium responsiveness. J Mol Cell Cardiol. 40(1):64-75, 2006.
7. Xuan YT, Guo Y, Zhu Y, Wang OL, Rokosh G, Messing RO, MD, Bolli R. Role of the protein kinase C-epsilon-Raf-1-MEK-1/2-p44/42 MAPK signaling cascade in the activation of signal transducers and activators of transcription 1 and 3 and induction of cyclooxygenase-2 after ischemic preconditioning. Circulation. 112(13):1971-19788, 2005
8. Tang XL, Takano H, Xuan YT, Sato H, Kodani E, Dawn B, Zhu Y, Shirk G, Wu WJ, Bolli R. Tang XL, Takano H, Xuan YT, Kodani E, Zhu Y, Shirk G, Wu WJ, and Bolli R. Hypercholesterolemia abrogates late preconditioning via a tetrahydrobiopterin-dependent mechanism in conscious rabbits. Circulation. 112(14):2149-56, 2005.
9. Dawn B, Xuan YT, Guo Y, Rezazadeh A, Stein AB, Hunt G, Wu WJ, Tan W, Bolli R. IL-6 plays an obligatory role in late preconditioning via JAK–STAT signaling and upregulation of iNOS and COX-2. Cardiovascular Research 64:61-71, 2004.
10. Li, QH., Guo, Y., Xuan YT., Lowenstein, CJ., Stevenson, SC., Prabhu, SD., Wu, WJ., Zhu, YQ., Bolli, R.: Gene therapy with inducible nitric oxide synthase protects against myocardial infarction via a cyclooxygenase-2-dependent mechanism. Circ Res, 92:741-748, 2003.
11. Xuan YT., Guo, Y., Zhu, Y., Han, H., Dawn B, Bolli, R.: Mechanism of cyclooxygenase-2 upregulation in late preconditioning. J Mol Cell Cardiol 35:525-37, 2003.
12. Bolli R, Dawn B, Xuan YT.: Role of the JAK-STAT pathway in protection against myocardial ischemia/reperfusion injury. Trends in Cardiovascular Medicine 13:72-79, 2003.
13. Shinmura K, Bolli R, Liu SQ, Tang XL, Kodani E, Xuan YT, Srivastava S, Bhatnagar A. Aldose reductase is an obligatory mediator of the late phase of ischemic preconditioning. Circ Res 91(3):240-6, 2002.
14. Kodani E, Xuan YT, Takano H, Shinmura K, Tang XL, Bolli R.: Role of cyclic guanosine monophosphate in late preconditioning in conscious rabbits. Circulation 105:3046-52, 2002.
15. Shinmura K, Xuan YT, Tang XL, Kodani E, Han H, Zhu Y, Bolli R. Inducible nitric oxide synthase modulates cyclooxygenase-2 activity in the heart of conscious rabbits during the late phase of ischemic preconditioning. Circ Res 90(5):602-608, 2002.
16. Bolli R, Dawn B, and Xuan YT.: Emerging role of the JAK-STAT pathway as a mechanism of protection against ischemia/reperfusion injury. J Mol Cell Cardiol 33(11):1893-6, 2001.
17. Xuan YT, Guo Y, Han H, Zhu Y, Bolli R.: An essential role of the JAK-STAT pathway in ischemic preconditioning. Proc Natl Acad Sci U S A 98(16):9050-5, 2001.
18. Dawn B, Xuan YT, Marian M, Flaherty MP, Murphree SS, Smith TL, Bolli R, and Jones WK. Cardiac-specific abrogation of NF-kB activation in mice by transdominant overexpression of a mutant IB. J. Mol. Cell. Cardiol. 33:161-173, 2001.
19. Xuan YT, Tang X-L, Qiu Y, Banerjee S, Takano H, Han H, Bolli R.: Biphasic response of cardiac NO synthase isoforms to ischemic preconditioning in conscious rabbits. Am J Physiol. 279(5):H2360-H2371, 2000.
20. Dawn B, Xuan YT, Qiu Y, Takano H, Tang X-L, Ping P, Banerjee S, Bolli R.: Bifunctional role of protein tyrosine kinases in late preconditioning against myocardial stunning in conscious rabbits. Circ Res. 85:1154-1163, 1999.
21. Xuan YT, Tang XL, Banerjee B, Takano H, Li RCX, Han H, Qiu Y, Li JJ, Bolli R. Nuclear factor kB plays an essential role in the late phase of ischemic preconditioning in conscious rabbits. Circ Res. 84:1095-1109, 1999.

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Division of Cardiovascular Medicine

Division of Cardiovascular Medicine

Dr. Xuan

Yu-Ting Xuan, Ph.D.

Professor of Medicine

Tel.: (502) 852-8428

E-mail: ytxuan01@louisville.edu

Selected Publication:

1. Hamid T, Gu Y, Ortines RV, Bhattacharya C, Wang G, Xuan YT, Prabhu SD. Diver Divergent Tumor Necrosis Factor Receptor–Related Remodeling Responses in Heart Failure Role of Nuclear Factor-kB and Inflammatory Activation. Circulation. 119:1386-1397, 2009.

4. Stein AB, Bolli R, Guo Y, Wang OL, Tan W, Wu WJ, Zhu XP, Zhu Y, Xuan YT. The late phase of ischemic preconditioning induces a prosurvival genetic program that results in marked attenuation of apoptosis. J Mol Cell Cardiol. 42:1075-1085, 2007.

5. West MB, Hill BG, Xuan YT, Bhatnagar A. Protein glutathiolation by nitric oxide: An intracellular mechanism regulating redox protein modification. FASEB J. 20(10):E1049-E1060, 2006.

6. Luo J, Xuan YT, Gu Y, Prabhu SD. Prolonged oxidative stress inverts the cardiac force-frequency relation: role of altered calcium handling and myofilament calcium responsiveness. J Mol Cell Cardiol. 40(1):64-75, 2006.

9. Dawn B, Xuan YT, Guo Y, Rezazadeh A, Stein AB, Hunt G, Wu WJ, Tan W, Bolli R. IL-6 plays an obligatory role in late preconditioning via JAK–STAT signaling and upregulation of iNOS and COX-2. Cardiovascular Research 64:61-71, 2004.

10. Li, QH., Guo, Y., Xuan YT., Lowenstein, CJ., Stevenson, SC., Prabhu, SD., Wu, WJ., Zhu, YQ., Bolli, R.: Gene therapy with inducible nitric oxide synthase protects against myocardial infarction via a cyclooxygenase-2-dependent mechanism. Circ Res, 92:741-748, 2003.

11. Xuan YT., Guo, Y., Zhu, Y., Han, H., Dawn B, Bolli, R.: Mechanism of cyclooxygenase-2 upregulation in late preconditioning. J Mol Cell Cardiol 35:525-37, 2003.

12. Bolli R, Dawn B, Xuan YT.: Role of the JAK-STAT pathway in protection against myocardial ischemia/reperfusion injury. Trends in Cardiovascular Medicine 13:72-79, 2003.

13. Shinmura K, Bolli R, Liu SQ, Tang XL, Kodani E, Xuan YT, Srivastava S, Bhatnagar A. Aldose reductase is an obligatory mediator of the late phase of ischemic preconditioning. Circ Res 91(3):240-6, 2002.

14. Kodani E, Xuan YT, Takano H, Shinmura K, Tang XL, Bolli R.: Role of cyclic guanosine monophosphate in late preconditioning in conscious rabbits. Circulation 105:3046-52, 2002.

15. Shinmura K, Xuan YT, Tang XL, Kodani E, Han H, Zhu Y, Bolli R. Inducible nitric oxide synthase modulates cyclooxygenase-2 activity in the heart of conscious rabbits during the late phase of ischemic preconditioning. Circ Res 90(5):602-608, 2002.

16. Bolli R, Dawn B, and Xuan YT.: Emerging role of the JAK-STAT pathway as a mechanism of protection against ischemia/reperfusion injury. J Mol Cell Cardiol 33(11):1893-6, 2001.

17. Xuan YT, Guo Y, Han H, Zhu Y, Bolli R.: An essential role of the JAK-STAT pathway in ischemic preconditioning. Proc Natl Acad Sci U S A 98(16):9050-5, 2001.

18. Dawn B, Xuan YT, Marian M, Flaherty MP, Murphree SS, Smith TL, Bolli R, and Jones WK. Cardiac-specific abrogation of NF-kB activation in mice by transdominant overexpression of a mutant IB. J. Mol. Cell. Cardiol. 33:161-173, 2001.

19. Xuan YT, Tang X-L, Qiu Y, Banerjee S, Takano H, Han H, Bolli R.: Biphasic response of cardiac NO synthase isoforms to ischemic preconditioning in conscious rabbits. Am J Physiol. 279(5):H2360-H2371, 2000.

20. Dawn B, Xuan YT, Qiu Y, Takano H, Tang X-L, Ping P, Banerjee S, Bolli R.: Bifunctional role of protein tyrosine kinases in late preconditioning against myocardial stunning in conscious rabbits. Circ Res. 85:1154-1163, 1999.

21. Xuan YT, Tang XL, Banerjee B, Takano H, Li RCX, Han H, Qiu Y, Li JJ, Bolli R. Nuclear factor kB plays an essential role in the late phase of ischemic preconditioning in conscious rabbits. Circ Res. 84:1095-1109, 1999.

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