DIVISION OF PULMONARY AND CRITICAL CARE MEDICINE
Faculty Clinical Programs Fellowship Program Research Facilities

Jason Yuan, MD, PhD

 

Jason X.-J. Yuan, MD, PhD
Professor of Medicine

 

 


 

INVESTIGATIVE INTERESTS:

      The overall interest of my laboratory is vascular physiology and pathophysiology, with particular emphasis on the regulation of excitation-contraction coupling in vascular smooth muscle, the cellular and molecular mechanisms of hypoxic pulmonary vasoconstriction, and the pathogenesis of pulmonary arterial hypertension (PAH).  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 calcium in regulating membrane potential, vasomotor tone, and pulmonary vascular smooth muscle cell 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: 1) to understand the cellular and molecular mechanisms involved in hypoxia-mediated inhibition of voltage-gated K+ channels in pulmonary artery smooth muscle cells; 2) to investigate the molecular mechanisms of vascular smooth muscle cell proliferation and apoptosis; 3) to specify the etiological roles of K+ and Ca2+ channels in PAH; 4) to examine cellular signal transduction mechanisms by which nitric oxide and prostacyclin induce vasodilation and apoptosis; 5) to search for new therapeutic approaches for pulmonary hypertension (e.g., K+ channel opener, pro-apoptotic and anti-proliferative agents); 6) to determine the genetic variances associated with the susceptibility to PAH in former users of fenfluramine or its derivatives and the genetic determinants affecting vasoreactivity in PAH patients in responses to vasodilators; and 7) to investigate the role of K+ channels and intracellular Ca2+ the regulation of intestinal and airway epithelial cell function (migration, proliferation, differentiation, and permeability).

EXPERIMENTAL APPROACHES AVAILABLE IN DR. YUAN’S LAB:

 

SELECTED PUBLICATIONS:

1.                  Golovina, V.A., O. Platoshyn, C.L. Bailey, J. Wang, A. Limsuwan, M. Sweeney, L.J. Rubin, and J.X.-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.                  McDaniel, S.S., O. Platoshyn, J. Wang, Y. Yu, M. Sweeney, S. Krick, L.J. Rubin, and J.X.-J. Yuan. Capacitative Ca2+ entry in agonist-induced pulmonary vasoconstriction.  Am. J. Physiol. Lung Cell. Mol. Physiol. 280:L870-L880, 2001.

3.                  Platoshyn, O., Y. Yu, V.A. Golovina, S.S. McDaniel, S. Krick, L. Li, J.-Y. Wang, L.J. Rubin, and J.X.-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.

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

5.                  Rao, J.N., L.Li, V.A. Golovina, O. Platoshyn, E.D. Strauch, J.X.-J. Yuan, and J.-Y. Wang.  Ca2+-RhoA signaling pathway required for polyamine-dependent intestinal epithelial cell migration.  Am.  J. Physiol. Cell Physiol. 280:C993-C1007, 2001.

6.                  Ekhterae, D., O. Platoshyn, S. Krick, Y. Yu, S.S. McDaniel, and J.X.-J. Yuan.  Bcl-2 decreases voltage-gated K+ channel activity and enhances survival in vascular smooth muscle cells.  Am. J.  Physiol. Cell Physiol. 281:C157-C178, 2001.

7.                  Limsuwan, A., O. Platoshyn, Y. Yu, L.J. Rubin, A. Rothman, and J.X.-J. Yuan.  Inhibition of K+ channel activity in pulmonary artery smooth muscle cells by serum from the patients with pulmonary hypertension secondary to congenital heart diseases.  Pediatr. Res. 50:23-28, 2001.

8.                  Krick, S., O. Platoshyn, S.S. McDaniel, L.J. Rubin, and J.X.-J. Yuan. Augmented K+ currents and mitochondrial membrane depolarization in pulmonary artery myocyte apoptosis.  Am. J. Physiol. Lung Cell. Mol. Physiol. 281:L887-L894, 2001.

9.                  McDaniel, S.S., O. Platoshyn, Y. Yu, M. Sweeney, V.A. Miriel, V.A. Golovina, S. Krick, Lapp BR, J.-Y. Wang, and J.X.-J. Yuan.  Anorexic effect of K+ channel blockade in mesenteric arterial smooth muscle and intestinal epithelial cells.  J. Appl. Physiol. 91:2322-2333, 2001.

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

11.              Krick, S., O. Platoshyn, M. Sweeney, S.S. McDaniel, S. Zhang, L.J. Rubin, and J.X.-J. Yuan. Nitric oxide induces apoptosis by activating K+ channels in pulmonary vascular smooth muscle cell.  Am. J. Physiol. Heart Circ. Physiol. 282:H184-H193, 2002.

12.              Rao, J.N., O. Platoshyn, L. Li, X. Guo, V.A. Golovina, J.X.-J. Yuan, and J.-Y. Wang.  Activation of K+ channels and increased migration of differentiated intestinal epithelial cells after wounding.  Am. J. Physiol. Cell Physiol. 282:C885-C898, 2002.

13.              Sweeney, M., S.S. McDaniel, O. Platoshyn, S. Zhang, Y. Yu, B.R. Lapp, Y. Zhao, P.A. Thistlethwaite, and J.X.-J. Yuan.  Role of capacitative Ca2+ entry in bronchial contraction and remodeling.  J. Appl. Physiol. 92:1594-1602, 2002.

14.              Sweeney, M., Y. Yu, O. Platoshyn, S. Zhang, S.S. McDaniel, and J.X.-J. Yuan. Inhibition of endogenous TRP1 decreases capacitative Ca2+ entry and attenuates pulmonary artery smooth muscle cell growth.  Am. J. Physiol. Lung Cell. Mol. Physiol. 283:L144-L155, 2002.

15.              Platoshyn, O., S. Zhang, S.S. McDaniel, and J.X.-J. Yuan. Cytochrome c activates K+ channels prior to inducing apoptosis.  Am. J. Physiol. Cell Physiol. 283:C1298-C1305, 2002.

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

17.              Du, L., C.C. Sullivan, D. Chu, A.J. Cho, M. Kido, P.L. Wolf, J.X.-J. Yuan, R. Deutsch, S.W. Jamieson, and P.A. Thistlethwaite. Signaling molecules in nonfamilial pulmonary hypertension. N. Engl. J. Med. 348(6):500-509, 2003.

18.              Rao, J.N., X. Guo, L. Liu, T. Zou, K. S. Murthy, J. X.-J. Yuan, and J.-Y. Wang. Polyamines regulate Rho-kinase and myosin phosphorylation during intestinal epithelial restitution. Am. J. Physiol. Cell Physiol. 284:C848-C859, 2003.

19.              Ekhterae, D., O. Platoshyn, S. Zhang, C.V. Remillard, and J.X.-J. Yuan. Apoptosis repressor with caspase domain inhibits cardiomycyte apoptosis by reducing K+ currents.  Am. J. Physiol. Cell Physiol. 284:C1405-C1515, 2003.

20.              Zhang, S., I. Fantozzi, D.D. Tigno, E.S. Yi, O. Platoshyn, P.A. Thistlethwaite, J.M. Kriett, G. Yung, L.J. Rubin, and J.X.-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.

21.              Fantozzi, I., S. Zhang, O. Platoshyn, C.V. Remillard, R.R. Cowling, and J.X.-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.

22.              Platoshyn, O., C.V. Remillard, I. Fantozzi, M. Mandegar, T. Sison, S. Zhang, E. Burg, and J.X.-J. Yuan. Diversity of voltage-dependent K+ channels in human pulmonary artery smooth muscle cells. Am. J. Physiol. Lung Cell. Mol. Physiol. In press, 2004.

 

 

LABORATORY MEMBERS AND THEIR RESEARCH PROJECTS:

Ann Nicholson, M.S., Staff Research Associate (annicholson@ucsd.edu)
             Pharmacogenomic study of primary pulmonary hypertension
Oleksandr (Alex) Platoshyn, M.S., Staff Research Associate (oplatoshyn@ucsd.edu)
            Electrophysiological studies on ion channel function
Steve H. Keller, Ph.D., Assistant Project Scientist (shkeller@ucsd.edu)
            Ion channel trafficking
Ivana Fantozzi, Ph.D., Postgraduate Researcher (ifantozzi@ucsd.edu)
            Transcriptional regulation of ion channel genes
 Mehran Mandegar, M.D., Postdoctoral Fellow (mandegarmd@yahoo.com)
            Expression and function of tandem pore potassium channels
 Carmelle V. Remillard, Ph.D., Postgraduate Researcher (cremillard@ucsd.edu)
            Electrophysiological and pharmacological properties of potassium channels
 Ying Yu, M.D., Ph.D., Postgraduate Researcher (yiyu@ucsd.edu)
            Gene expression of TRP channels and cell proliferation
 Shen Zhang, M.D., Ph.D., Postgraduate Researcher (szhang@ucsd.edu)
            Intracellular calcium regulation and cell apoptosis
Donna Tigno, M.D., Postdoctoral Fellow (dtigno@yahoo.com)
            Novel SNP discoveries in genes implicated in primary pulmonary hypertension
Judd Landsberg, M.D., Postdoctoral Fellow (judd_sarita@yahoo.com)
            Molecular determinants of pulmonary vascular smooth muscle remodeling
Nivruthi Vangala, Student
            Genetic variations in TRPC6 gene of patients with pulmonary arterial hypertension
Michelle M. Le, Student
            Novel SNPs in bone morphogenetic protein receptor type II gene  
Joseph R. Mauban, Ph.D., Postgraduate Researcher ()
            Mechanisms of intracellular Ca2+ regulation in smooth muscle and endothelial cells
Diane A. Conger, B.S., Staff Research Associate (damcintyre@ucsd.edu)
            Clinical study on pulmonary arterial hypertension

LABORATORY  MEMBERS

 

ACTIVE GRANT SUPPORT:

1. NIH/NHLBI (1R01 HL 64945; Principal Investigator: J. Yuan); "Cellular Mechanisms of PPH: Role of K+ Channels” (1999 - 2008).
2. NIH/NHLBI (2R01 HL 54043; Principal Investigator: J. Yuan); "Ion Channels and Pulmonary Vascular Tone" (2000 - 2005).
3.

 

NIH/NHLBI (1U01 HL69758; Project I Principal Investigators: L.J. Rubin and J. Yuan); “Autonomic Pharmacodynamic Pharmacogenomics - Pulmonary Vascular Responses in Primary Pulmonary Hypertension” (2001- 2005).
4. NIH/NHLBI (1R01 HL66012; Principal Investigator: J Yuan); “Capacitative Calcium Entry in Pulmonary Myocyte Growth” (2001 - 2006).

For more information write to Dr. Jason Yuan (xiyuan@ucsd.edu) or Ms. Ann Nicholson (annicholson@ucsd.edu).

Lab Location:

Clinical Teaching Facility
(CTF, Room A-211)
UCSD Medical Center
210A Dickinson Street
San Diego, CA 92103-8382
Tel:(619)543-2882
Fax: (619)543-3442.

 Mailing Address:

Division of Pulmonary and Critical Care Medicine
Department of Medicine (8382)
University of California, San Diego
200 W. Arbor Dr.
San Diego, CA 92103-8382.
Tel: (619)543-2878
Fax: (619)543-2929