Jason X.-J. Yuan, MD, PhD

Professor of Medicine

Associate Director for Research Training (Basic Science)

Click here to view Jason X.-J. Yuan's Lab

Main Research Interests

The overall interest of the laboratory is vascular physiology and pathophysiology and pathogenic mechanisms of pulmonary vascular disease, with particular emphasis on

• the regulation of excitation-contraction coupling in vascular smooth muscle,
• the cellular and molecular mechanisms of hypoxic pulmonary vasoconstriction,
• the pathogenic and therapeutic mechanisms of idiopathic and thromboembolic pulmonary hypertension.

By using the combined techniques of patch clamp, digital imaging fluorescence microscopy, and molecular biology, we are currently studying the roles of ion channels and intracellular Ca2+ in regulating vasomotor tone, and pulmonary vascular smooth muscle proliferation and apoptosis. Furthermore, whether the endothelium-derived relaxing factors result in vasodilation and apoptosis by regulating function and expression of ion channels is also being investigated.

The aims of the ongoing research work in the laboratory are:

• Understand the cellular and molecular mechanisms involved in hypoxia-mediated inhibition of voltage-gated K+ channels in pulmonary artery smooth muscle cells (PASMC)
• Investigate the molecular mechanisms of PASMC proliferation and apoptosis
• Specify the etiological roles of K+ and Ca2+ channels in pulmonary arterial hypertension
• Search for new therapeutic approaches for pulmonary arterial hypertension (e.g., K+ channel openers, pro-apoptotic/anti-proliferative agents)
• Determine the genetic variances
• associated with the susceptibility to develop idiopathic and thromboembolic pulmonary hypertension
• affecting vasoreactivity to clinically-used vasodilators in patients with pulmonary arterial hypertension
• Identify the mechanisms that regulate membrane trafficking of ion channels in pathogenesis.

Awards

Contact Dr. Jason Yuan:  Xiyuan@ucsd.edu

Contact the Lab:  Tel: (858) 822-6534
                            Fax: (858) 822-6531

Publications

Representative Publications

1. Golovina VA, O Platoshyn, CL Bailey, J Wang, A Limsuwan, M Sweeney, LJ Rubin, and JX-J Yuan. Upregulated TRP and enhanced capacitative Ca2+ entry in human pulmonary artery myocytes during proliferation. Am J Physiol Heart Circ Physiol 280: H746-H755, 2001.

2. Krick S, O Platoshyn, M Sweeney, H Kim, and JX-J Yuan. Activation of K+ channels induces apoptosis in vascular smooth muscle cells. Am J Physiol Cell Physiol 280: C970-C979, 2001.

3. McDaniel SS, O Platoshyn, J Wang, Y Yu, M Sweeney, S Krick, LJ Rubin, and JX-J Yuan. Capacitative Ca2+ entry in agonist-induced pulmonary vasoconstriction. Am J Physiol Lung Cell Mol Physiol 280: L870-L880, 2001.

4. Platoshyn O, Y Yu, VA Golovina, SS McDaniel, S Krick, L Li, JY Wang, LJ Rubin, and JX-J Yuan. Chronic hypoxia decreases KV channel expression and function in pulmonary artery myocytes. Am J Physiol Lung Cell Mol Physiol 280: L801-L812, 2001.

5. Yu Y, O Platoshyn, J Zhang, S Krick, Y Zhao, LJ Rubin, A Rothman, and JX-J Yuan. c-Jun decreases voltage-gated K+ channel activity in pulmonary artery smooth muscle cells. Circulation 104: 1557-1563, 2001.

6. Platoshyn O, S Zhang, SS McDaniel, and JX-J Yuan. Cytochrome c activates K+ channels before inducing apoptosis. Am J Physiol Cell Physiol 283: C1298-C1305, 2002.

7. Fantozzi I, S Zhang, O Platoshyn, CV Remillard, RT Cowling, and JX-J Yuan. Hypoxia increases AP-1 binding activity by enhancing capacitative Ca2+ entry in human pulmonary artery endothelial cells. Am J Physiol Lung Cell Mol Physiol 285: L1233-L1245, 2003.

8. Yu Y, M Sweeney, S Zhang, O Platoshyn, J Landsberg, A Rothman, and JX-J Yuan. PDGF stimulates pulmonary vascular smooth muscle cell proliferation by upregulating TRPC6 expression. Am J Physiol Cell Physiol 284: C316-C330, 2003.

9. Zhang S, I Fantozzi, DD Tigno, ES Yi, O Platoshyn, PA Thistlethwaite, JM Kriett, G Yung, LJ Rubin, and JX-J Yuan. Bone morphogenetic proteins induce apoptosis in human pulmonary vascular smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 285: L740-L754, 2003.

10. Kunichika N, JW Landsberg, Y Yu, H Kunichika, PA Thistlethwaite, LJ Rubin, and JX-J Yuan. Bosentan inhibits transient receptor potential channel expression in pulmonary vascular myocytes. Am J Respir Crit Care Med 170: 1101-1107, 2004.

11. Platoshyn O, CV Remillard, I Fantozzi, M Mandegar, TT Sison, S Zhang, E Burg, and JX-J Yuan. Diversity of voltage-dependent K+ channels in human pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 287: L226-L238, 2004.

12. Yu Y, I Fantozzi, CV Remillard, JW Landsberg, N Kunichika, O Platoshyn, DD Tigno, PA Thistlethwaite, LJ Rubin, and JX-J Yuan. Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension. Proc Natl Acad Sci USA 101: 13861-13866, 2004.

13. Fantozzi I, W Huang, J Zhang, S Zhang, O Platoshyn, CV Remillard, PA Thistlethwaite, and JX-J Yuan. Divergent effects of BMP-2 on gene expression in pulmonary artery smooth muscle cells from normal subjects and patients with idiopathic pulmonary arterial hypertension. Exp Lung Res 31: 783-806, 2005.

14. Zhang S, JX-J Yuan, KE Barrett, and H Dong. Role of Na+/Ca2+ exchange in regulating cytosolic Ca2+ in cultured human pulmonary artery smooth muscle cells. Am J Physiol Cell Physiol 288: C245-C252, 2005.

15. Fantozzi I, O Platoshyn, AH Wong, S Zhang, CV Remillard, MR Furtado, OV Petrauskene, and JX-J Yuan. Bone morphogenetic protein-2 upregulates expression and function of voltage-gated K+ channels in human pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 291: L993-L1004, 2006.

16. Ko EA, ED Burg, O Platoshyn, J Msefya, AL Firth, and JX-J Yuan. Functional characterization of voltage-gated K+ channels in mouse pulmonary artery smooth muscle cells. Am J Physiol Cell Physiol 293: C928-C937, 2007.

17. Remillard CV, DD Tigno, O Platoshyn, ED Burg, EE Brevnova, D Conger, A Nicholson, BK Rana, RN Channick, LJ Rubin, DT O'Connor, and -J Yuan. Function of Kv1.5 channels and genetic variations in KCNA5 in patients with idiopathic pulmonary arterial hypertension. Am J Physiol Cell Physiol 292: C1837-C1853, 2007.

18. Wu W, O Platoshyn, AL Firth, and JX-J Yuan. Hypoxia divergently regulates production of reactive oxygen species in human pulmonary and coronary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 293: L952-L959, 2007.

19. Zhang S, HH Patel, F Murray, CV Remillard, C Schach, P Thistlethwaite, PA Insel, and JX-J Yuan. Pulmonary artery smooth muscle cells from normal subjects and IPAH patients show divergent cAMP-mediated effects on TRPC expression and capacitative Ca2+ entry. Am J Physiol Lung Cell Mol Physiol 292: L1202-L1210, 2007.

20. Schach C, AL Firth, M Xu, CV Remillard, HH Patel, PA Insel, and JX-J Yuan. Regulation of pulmonary vasoconstriction by agonists and caveolae. Exp Lung Res 34: 195-208, 2008.

21. Xu M, O Platoshyn, A Makino, WH Dillmann, K Akassoglou, CV Remillard, and JX-J Yuan. Characterization of agonist-induced vasoconstriction in mouse pulmonary artery. Am J Physiol Heart Circ Physiol 294: H220-H228, 2008.

22. Schach C, AL Firth, M Xu, CV Remillard, HH Patel, PA Insel, and JX-J Yuan. Regulation of pulmonary vasoconstriction by agonists and caveolae. Exp Lung Res 34:195-208, 2008.

23. Remillard CV and JX-J Yuan. Characterization of hemodynamics in patients with idiopathic and thromboembolic pulmonary hypertension. Clin Med Circ Respir Pul Med. 2:59-68, 2008.

24. Ogawa A, AL Firth, W Yao, LJ Rubin, and JX-J Yuan. Prednisolone inhibits PDGF-induced nuclear translocation of NF-κB in human pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 295:L648-L657, 2008.

25. Sacks RS, AL Firth, CV Remillard, N Agange, J Yau, EA Ko, and JX-J Yuan. Thrombin-induced increases in cytosolic [Ca2+] involve different mechanisms in human pulmonary artery smooth muscle and endothelial cells. Am J Physiol Lung Cell Mol Physiol In press, 2008.