Jason X.-J. Yuan, MD, PhD

Professor of Medicine

Publications | Lab Members | Techniques | Research / Collaboration

Division of Pulmonary & Critical Care Medicine
Department of Medicine
University of California, San Diego
9500 Gilman Drive, MC 0725
La Jolla, California 92093-0725

Tel: (858) 822-6534
Fax: (858) 822-6531
E-mail: xiyuan@ucsd.edu

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.

Research Areas on PDF

Electrophysiology
Flow Cytometry
Fluorescence
Molecular Biology
SNP
Tension

Publications

Original Articles

1.  Ekhterae D, Platoshyn O, Krick S, Yu Y, McDaniel SS, and Yuan JX-J. Bcl-2 decreases voltage-gated K+ channel activity and enhances survival in vascular smooth muscle cells. Am J Physiol Cell Physiol 281: C157-C165, 2001. {AJP Cell Physiol}

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

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

4.  Limsuwan A, Platoshyn O, Yu Y, Rubin LJ, Rothman A, and Yuan JX-J. Inhibition of K+ channel activity in human pulmonary artery smooth muscle cells by serum from patients with pulmonary hypertension secondary to congenital heart disease. Pediatr Res 50: 23-28, 2001. {Pediatr Res}

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

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

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

8.  Rao JN, Li L, Golovina VA, Platoshyn O, Strauch ED, Yuan JX-J, and Wang J-Y. Ca2+-RhoA signaling pathway required for polyamine-dependent intestinal epithelial cell migration. Am J Physiol Cell Physiol 280: C993-C1007, 2001. {AJP Cell Physiol}

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

10.  Krick S, Platoshyn O, Sweeney M, McDaniel SS, Zhang S, Rubin LJ, and Yuan JX-J. Nitric oxide induces apoptosis by activating K+ channels in pulmonary vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 282: H184-H193, 2002. {AJP Heart Circ Physiol}

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

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

13.  Du L, Sullivan CC, Chu D, Cho AJ, Kido M, Wolf PL, Yuan JX-J, Deutsch R, Jamieson SW, and Thistlethwaite PA. Signaling molecules in nonfamilial pulmonary hypertension. N Engl J Med 348: 500-509, 2003. {NEJM}

14.  Fantozzi I, Zhang S, Platoshyn O, Remillard CV, Cowling RT, and Yuan JX-J. 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. {AJP Lung Cell Mol Physiol}

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

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

17.  Brevnova EE, Platoshyn O, Zhang S, and Yuan JX-J. Overexpression of human KCNA5 increases IK(V) and enhances apoptosis. Am J Physiol Cell Physiol 287: C715-C722, 2004. {AJP Cell Physiol}

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

19.  Kunichika N, Yu Y, Remillard CV, Platoshyn O, Zhang S, and Yuan JX-J. Overexpression of TRPC1 enhances pulmonary vasoconstriction induced by capacitative Ca2+ entry. Am J Physiol Lung Cell Mol Physiol 287: L962-L969, 2004. {AJP Lung Cell Mol Physiol}

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

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

22.  Zhang S, Remillard CV, Fantozzi I, and Yuan JX-J. ATP-induced mitogenesis is mediated by CREB-enhanced TRPC4 expression and activity in human pulmonary artery smooth muscle cells. Am J Physiol Cell Physiol 287: C1192-C1204, 2004. {AJP Cell Physiol}

23.  Fantozzi I, Huang W, Zhang J, Zhang S, Platoshyn O, Remillard CV, Thistlethwaite PA, and Yuan JX-J. 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. {Exp Lung Res}

24.  Keller SH, Platoshyn O, and Yuan JX-J. Long QT syndrome-associated I593R mutation in HERG potassium channel activates ER stress pathways. Cell Biochem Biophys 43: 365-377, 2005. {Cell Biochem Biophys}

25.  Platoshyn O, Remillard CV, Fantozzi I, Sison T, and Yuan J. Identification of functional voltage-gated Na+ channels in cultured human pulmonary artery smooth muscle cells. Pflügers Arch - Eur J Physiol 451: 380-387, 2005. {Pflügers}

26.  Tsigelny I, Hotchko M, Yuan JX-J, and Keller SH. Identification of molecular determinants that modulate trafficking of DF508 CFTR, the mutant ABC transporter associated with cystic fibrosis. Cell Biochem Biophys 42: 41-53, 2005. {Cell Biochem Biophys}

27.  Zhang S, Yuan JX-J, Barrett KE, and Dong H. 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. {AJP Cell Physiol}

28.  Fantozzi I, Platoshyn O, Wong AH, Zhang S, Remillard CV, Furtado MR, Petrauskene OV, and Yuan JX-J. 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. {AJP Lung Cell Mol Physiol}

29.  Mauban JRH, Wilkinson K, Schach C, and Yuan JX-J. Histamine-mediated increase in cytosolic [Ca2+] involve different mechanisms in human pulmonary artery smooth muscle and endothelial cells. Am J Physiol Cell Physiol 290: C325-C336, 2006. {AJP Cell Physiol}

30.  Platoshyn O, Brevnova EE, Burg ED, Yu Y, Remillard CV, and Yuan JX-J. Acute hypoxia selectively inhibits KCNA5 channels in pulmonary artery smooth muscle cells. Am J Physiol Cell Physiol 290: C907-C916, 2006. {AJP Cell Physiol}

Reviews & Editorials

1.  Yuan JX-J. Oxygen-sensitive K+ channel(s): where and what? Am J Physiol Lung Cell Mol Physiol 281: L1345-L1349, 2001. {AJP Lung Cell Mol Physiol}

2.  Mandegar M, Remillard CV, and Yuan JX-J. Ion channels in pulmonary arterial hypertension. Prog Cardiovasc Dis 45: 81-114, 2002. {Prog Cardiovasc Dis}

3.  Mandegar M and Yuan JX-J. Role of K+ channels in pulmonary hypertension. Vascul Pharmacol 38: 25-33, 2002. {Vascul Pharmacol}

4.  Landsberg JW and Yuan JX-J. Calcium and TRP channels in pulmonary vascular smooth muscle cell proliferation. News Physiol Sci 19: 47-52, 2004. {NiPS}

5.  Mandegar M, Fung Y-CB, Huang W, Remillard CV, Rubin LJ, and Yuan JX-J. Cellular and molecular mechanisms of pulmonary vascular remodeling: role in the development of pulmonary hypertension. Microvasc Res 68: 75-103, 2004. {Microvasc Res}

6.  Remillard CV and Yuan JX-J. Activation of K+ channels: An essential pathway in programmed cell death. Am J Physiol Lung Cell Mol Physiol 286: L49-L67, 2004. {AJP Lung Cell Mol Physiol}

7.  Mauban J, Remillard CV, and Yuan JX-J. Hypoxic pulmonary vasoconstriction: Role of ion channels. J Appl Physiol 98: 415-420, 2005. {J Appl Physiol}

8.  Remillard CV and Yuan JX-J. High altitude pulmonary hypertension: Role of K+ and Ca2+ channels. High Alt Med Biol 6: 133-146, 2005. {High Alt Med Biol}

9.  Remillard CV and Yuan JX-J. PGE2 and PAR-1 in pulmonary fibrosis: a case of biting the hand that feeds you? Am J Physiol Lung Cell Mol Physiol 288: L789-L792, 2005. {AJP Lung Cell Mol Physiol}

10.  Yuan JX-J and Rubin LJ. Pathogenesis of pulmonary arterial hypertension: The need for multiple hits. Circulation 111: 534-538, 2005. {Circulation}

11.  Burg ED, Remillard CV, and Yuan JX-J. K+ channels in apoptosis. J Membr Biol 209: 3-20, 2006. {Pflügers}

12.  Remillard CV and Yuan JX-J. Transient receptor potential channels and caveolin-1: good friends in tight spaces. Mol Pharmacol 70: 1151-1154, 2006. {Mol Pharmacol}

13.  Sacks RS, Remillard CV, Agange N, Auger WR, Thistlethwaite PA, and Yuan JX-J. Molecular biology of chronic thromboembolic pulmonary hypertension. Semin Cardiovasc Thorac Surg: in press, 2006.

Books

Yuan JX-J (Ed). Ion Channels in the Pulmonary Vasculature. Taylor & Francis; London, UK: 2005.

Yuan JX-J (Ed). Hypoxic Pulmonary Vasoconstriction: Cellular and Molecular Mechanisms. Kluwer; Boston, MA: 2004.

EXPERIMENTAL APPROACHES AVAILABLE IN DR. YUAN’S LAB:

Lab Members

Steve H. Keller, Ph.D.

Assistant Project Scientist

shkeller@ucsd.edu

Ion Channel Trafficking

Carmelle V. Remillard, Ph.D.

Assistant Project Scientist

cremillard@ucsd.edu

Electrophysiological and Pharmacological

Properties of K+ Channels

Eun A Ko, Ph.D.

Postgraduate Researcher

eko@ucsd.edu

Functional Role of K+ and Ca2+ Channels

in the Development of Thromboembolic

Pulmonary Hypertension

Oleksandr (Alex) Platoshyn, M.S.

Staff Research Associate

oplatoshyn@ucsd.edu

Electrophysiological Studies on Ion

Channel Function

Elyssa D. Burg, B.A.

Ph.D. Student

eburg@ucsd.edu

Role of K+ Channels in

Pulmonary Hypertension

Richard Sacks, M.D.

Pulmonary Fellow

risacks@ucsd.edu

Role of Protease-activated Receptors

In Chronic Thromboembolic

Pulmonary Hypertension

Aiko Ogawa, Ph.D.

Visiting Cardiology Fellow

aiogawa@ucsd.edu

Regulation of TRPC Channels by

Prednisolone: Role in Pulmonary

Arterial Hypertension

Past Trainees

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

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).