Research Interests

Yuan Laboratory is a translational research lab currently focused on cardiopulmonary and vascular pathobiology, ion channel electrophysiology, and the pathogenic mechanisms of pulmonary vascular disease. The Laboratory uses the patch clamp technique, digital imaging fluorescence microscopy, conventional cellular and molecular biology techniques, and genetic and genomic analyses to investigate the roles of ion channels (e.g., K⁺ and Ca²⁺ channels), membrane receptors (e.g., GPCR/CaSR, Notch receptors), and intracellular Ca²⁺ signaling in regulating vasomotor tone, and pulmonary vascular smooth muscle cell contraction/relaxation, migration, proliferation/apoptosis in order to understand the molecular mechanisms involved in idiopathic pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). The aim of our investigation is to define pathogenic mechanisms and identify new therapeutic targets and treatment strategies for pulmonary hypertension and right heart failure.

Dr. Yuan’s teaching efforts are in the Wertheim UF Scripps Institute and the UF College of Medicine for mentoring undergraduate students, graduate students, medical students, postdoctoral clinical and research fellows and junior faculty members for translational research in the field of pulmonary circulation and lung vascular disease. He is also actively involved in supporting career development and professional training through various professional associations like The American Physiological Society, American Thoracic Society and American Heart Association. The Laboratory members include junior faculty members, visiting scholars, postdoctoral fellows, graduate students, and undergraduate students.

Publications hIGHLIGHTS

Books

Yuan JX (ed) Hypoxic Pulmonary Vasoconstriction: Cellular and Molecular Mechanisms. Kluwer Academic Publishers, Boston, MA, 2004 (608 pages). ISBN: 978-1-4020-7857-6.

Yuan JX (ed) Ion Channels in the Pulmonary Vasculature. Taylor & Francis Group, Boca Raton, FL, 2005 (832 pages). ISBN-13: 978-0-8247-5968-1.

Yuan JX and Ward JPT (eds) Membrane Receptors, Channels, and Transporters in Pulmonary Circulation. Humana Press-Springer, New York, NY, 2010 (501 pages). ISBN: 978-1-60761-499-9.

Yuan JX, Garcoa JGN, Hales CA, Rich S, Archer SL, and West JB (eds) Textbook of Pulmonary Vascular Disease. Springer, New York, NY. 2011 (1,658 pages, 590 illus., 245 in color). ISBN: 978-0-387-87428-9.

Firth A and Yuan JX (eds) Lung Stem Cells in the Epithelium and Vasculature. Humana Press/Springer Cham Heidelberg New York Dordrecht London, 2015 (345 pages). ISBN: 978-3-319-16231-7 (Print) 978-3-319-16232-4 (Online/eBook)

Barrett KE, Barman SM, Brooks HL and Yuan JX. Ganong’s Review of Medical Physiology (26^th Edition). McGraw Hill/Lange, New York, NY, 2019 (742 pages).  ISBN: 978-1-260-566666-6; MHID: 1-260-56666-8.

Barrett KE, Barman SM, Brooks HL and Yuan JX. Ganong’s Physiology Examination & Board Review (2^nd Edition). McGraw Hill/Lange, New York, NY, 2024 (ISBN 978-1-264-26430-8; MHID 1-264-26430-5.

Original Research Articles

1. Yuan JX, Aldinger AM, Juhaszova M, Wang J, Conte JV, Gaine SP, Orens JB, and Rubin LJ. Dysfunctional voltage-gated K⁺ channels in pulmonary artery smooth muscle cells of patients with primary pulmonary hypertension. Circulation 98: 1400-1406, 1998. PMID: 9760294. No PMCID.
2. Yuan XJ, Wang J, Juhaszova M, Gaine SP, and Rubin LJ. Attenuated K⁺ channel gene transcription in primary pulmonary hypertension. Lancet 1998 Mar 7;351(9104):726-7, 1998. PMID: 9504523. No PMCID.
3. Wang J, Juhaszova M, Conte JV, Gaine SP, Rubin LJ, and Yuan JX. Action of fenfluramine on voltage-gated K⁺ channels in human pulmonary-artery smooth-muscle cells. Lancet 352: 290, 1998. PMID: 9690417. No PMCID.
4. Yu Y, Platoshyn O, Zhang J, Krick S, Zhao Y, Rubin LJ, Rothman A, and Yuan JX. c-Jun decreases voltage-gated K⁺ channel activity in pulmonary artery smooth muscle cells. Circulation 104: 1557-1563, 2001. PMID: 11571252. No PMCID.
5. Yu Y, Fantozzi I, Remillard CV, Landsberg JW, Kunichika N, Platoshyn O, Tigno DD, Thistlethwaite PA, Rubin LJ and Yuan JX. Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension. Proc Natl Acad Sci USA 101: 13861-13866, 2004. PMCID: PMC518765.
6. Laugwitz K-L, Moretti A, Lam J, Gruber P, Chen Y, Woodard S, Lin L-Z, Cai C-L, Lu MM, Reth M, Platoshyn O, Yuan JX, Evans S and Chien KR. Postnatal isl¹⁺ cardioblasts enter fully differentiated cardiomyocyte lineages. Nature 433: 647-653, 2005. PMCID: PMC5578466.
7. Yu Y, Keller SH, Remillard CV, Safrina O, Nicholson A, Zhang SL, Jiang W, Vangala N, Landsberg JW, Wang J-Y, Thistlethwaite PA, Channick RN, Robbins IM, Loyd JE, Ghofrani HA, Grimminger F, Schermuly RT, Cahalan MD, Rubin LJ, and Yuan JX. A functional single nucleotide polymorphism in the TRPC6 gene promoter associated with idiopathic pulmonary arterial hypertension. Circulation 119: 2313-2322, 2009. PMCID: PMC2749566.
8. Yao W, Firth AL, Sacks RS, Ogawa A, Auger WR, Fedullo PF, Madani MM, Sakakibara N, Lin GY, Thistlethwaite PA, Jamieson SW, Rubin LJ and Yuan JX. Identification of putative endothelial progenitor cells (CD34⁺CD133⁺Flk-1⁺) in endarterectomized tissue of patients with chronic thrombo-embolic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 296: L870-L878, 2009. PMCID: PMC2692803.
9. Firth Al, Yao W, Remillard CV, Ogawa A and Yuan JX. Upregulation of Oct-4 isoforms in pulmonary artery smooth muscle cells from patients with pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol 298: L548-L557, 2010. PMCID: PMC2853339.
10. Firth AL, Yao W, Ogawa A, Madani MM, Lin GY and Yuan JX. Multipotent mesenchymal progenitor cells are present in endarterectomized tissues from patients with chronic thromboembolic pulmonary hypertension. Am J Physiol Cell Physiol 298: C1217-C1225, 2010. PMCID: PMC2867379.
11. Ogawa A, Firth AL, Smith KA, Maliakal MV, Yuan JX. PDGF enhances store-operated Ca²⁺ entry by upregulating STIM1/Orai1 via activation of Akt/mTOR in human pulmonary arterial smooth muscle cells. Am J Physiol Cell Physiol. 302(2):C405-C411, 2012. PMID: 22031597. PMCID: PMC3328839.
12. Yamamura A, Guo Q, Yamamura H, Zimnicka AM, Pohl NM, Smith KA, Fernandez RA, Zeifman A, Makino A, Dong H, and Yuan JX. Enhanced Ca²⁺-sensing receptor function in pulmonary arterial hypertension. Circ Res 111:469-481, 2012. PMCID: PMC3695473
13. Tang H, Chen J, Fraidenburg DR, Song S, Sysol JR, Drennan AR, Offermanns S, Ye RD, Bonini MG, Minshall RD, Garcia JG, Machado RF, Makino A, Yuan JX. Deficiency of Akt1, but not Akt2, attenuates the development of pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 308(2):L208-L220, 2015. PMID: 25416384. PMCID: PMC4338938.
14. Song S, Yamamura A, Yamamura H, Babicheva A, Ayon RJ, Dash S, Sun X, Tang H, Black SM, Desai A, Rischard F, McDermott KM, Makino A, and Yuan JX. Capsaicin-induced Ca²⁺ signaling is enhanced via overexpressed TRPV1 channels in pulmonary arterial smooth muscle cells from patients with idiopathic pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol 312: L309-L325, 2017. PMCID: PMC5374303.
15. Song S, Carr SG, McDermott KM, Rodriguez M, Babicheva A, Balistrieri A, Ayon RJ, Wang J, Makino A, and Yuan JX. STIM2-mediated increase in resting [Ca²⁺]_cyt stimulates PASMC proliferation in pulmonary arterial hypertension. Hypertension. 71: 518-529, 2018. PMCID: PMC5955710.
16. Tang H, Wu K, Wang J, Vinjamuri S, Gu Y, Song S, Wang Z, Zhang Q, Balistrieri A, Ayon RJ, Rischard F, Vanderpool R, Chen J, Zhou G, Desai AA, Black SM, Garcia JGN, Yuan JX, Makino A. Pathogenic role of mTORC1 and mTORC2 in pulmonary hypertension. JACC Basic Transl Sci. 3(6):744-762, 2018. PMID: 30623134. PMCID: PMC6314964.
17. Tang H, K. Wu K, Wang J, Vinjamuri S, Gu Y, Song S, Wang Z, Zhang Q, Balistrieri A, Ayon RJ, Rischard F, Vanderpool R, Chen J, Zhou G, Desai AA, Black SM, Garcia JGN, Yuan JX, and Makino A. Pathogenic role of mTORC1 and mTORC2 in pulmonary hypertension. JACC. Basic Trans. Sci. 3(6):744-762, 2018.
18. Babicheva A, Ayon RJ, Zhao T, Ek Vitorin JF, Pohl NM, Yamamura A, Yamamura H, Quinton BA, Ba M, Wu L, Ravellette KS, Rahim S, Balistrieri F, Harington A, Vanderpool RR, Thistlethwaite PA, Makino A and Yuan JX. MicroRNA-mediated downregulation of K⁺ channels in pulmonary arterial hypertension. Am. J. Physiol. Lung Cell Mol. Physiol. 318(1):L10-L26, 2020. PMID: 31553627.
19. Song S, Babicheva A, Zhao T, Ayon RJ, Rodriguez M, Rahimi S, Balistrieri F, Harrington A, Shyy JY, Thistlethwaite PA, Makino A and Yuan JX. Notch enhances Ca²⁺ entry by activating calcium-sensing receptor and inhibiting voltage-gated K⁺ channels. Am. J. Physiol. Cell Physiol. 318(5):C954-C968, 2020. PMID: 32186932
20. Shen H, Zhang J, Wang C, P.P. Jain PP, Xiong M, Shi X, Lei Y, Chen S, Yin Q, Thistlethwaite PA, Wang J, Gong K, Yuan Z-Y, Yuan JX, and Shyy JY-J. MDM2-mediated ubiquitination of ACE2 contributes to the development of pulmonary arterial hypertension. Circulation. 142(12):1190-1204, 2020. PMID: 32755395.
21. Lei Y, Zhang J, Schiavon CR, He M, Chen L, Shen H, Zhang Y, Yin Q, Cho Y, Andrade L, Shadel GS, Hepokoski M, Lei T, Wang H, Zhang J, Yuan JX, Malhotra A, Manor U, Wang S, Yuan Z-Y, and Shyy JY-J. SARS-CoV-2 spike protein impairs endothelial function via downregulation of ACE2. Circ Res. 128(9):1323-1326, 2021. PMID: 33784827
22. Wang Z, Chen J, Babicheva A, Jain PP, Rodriguez M, Ayon RJ, Ravellette KS, Wu L, Rehim S, Balistrieri F, Tang H, Wu X, Black SM, Desai AA, Garcia JGN, Sun X, Shyy JY-J, Valdez-Jasso D, Thistlethwaite PA, Makino A, Wang J, and Yuan JX. Endothelial upregulation of mechanosensitive channel Piezo1 in pulmonary hypertension. Am. J. Physiol. Cell Physiol. 321(6):C1010-C1027, 2021. PMID: 34669509.
23. Jain PP, Lai N, Xiong M, Chen J, Babicheva A, Zhao T, Parmisano S, Zhao M, Paquin C, Matti M, Powers R, Balistrieri A, Kim NH, Valdez-Jasso D, Thistlethwaite PA, Shyy JY-J, Wang J, Garcia JGN, Makino A and Yuan JX. TRPC6, a therapeutic target for pulmonary hypertension. Am. J. Physiol. Lung Cell Mol. Physiol. 321(6):L1161-L1182, 2021. PMID: 34704831
24. Chen J, Rodriguez M, Miao J, Liao K, Jain PP, Zhao M, Zhao T, Babicheva A, Wang Z, Parmisano S, Powers R, Matti M, Paquin C, Soroureddin Z, Shyy JY-J, Thistlethwaite PA, Makino A, Wang J, and Yuan JX. Mechanosensitive channel Piezo1 is required for pulmonary artery smooth muscle cell proliferation. Am. J. Physiol. Lung Cell. Mol. Physiol. 322(5):L737-L760, 2022. PMID: 35318857.
25. Zhang Y, Hernandez M, Gower J, Winicki N, Morataya X, Alvarez X, Yuan JX, Shyy JY-J, and Thistlethwaite PA. JAGGED-NOTCH3 signaling in vascular remodeling in pulmonary arterial hypertension. Sci. Transl. Med. 14(643):eabl5471, 2022. PMID: 35507674.
26. Zhao T, Parmisano S, Soroureddin Z, Wang M, Yung L, Thistlethwaite PA, Makino A, and Yuan JX. Mechanosensitive cation currents through TRPC6 and Piezo1 channels in human pulmonary arterial endothelial cells. Am. J. Physiol. Cell Physiol. 323(4):C959-C973, 2022. PMID: 35968892
27. Wang C, Xing Y, Zhang J, He M, Dong J, Chen S, Wu H, Huang H-Y, Chou C-H, Bai L, He F, She J, Su A, Wang Y, Thistlethwaite PA, Huang H-D, Yuan JX, Yuan Z-Y, Shyy JY-. MED1 regulates BMP/TGF-β in endothelium: Implications for pulmonary hypertension. Circ. Res. 131(10):828-841, 2022. PMID: 36252121
28. Stokes G, Li Z, Talaba N, Genthe W, Brix MB, Pham B, Wienhold MD, Sandok G, Hernan R, Wynn J, Tang H, Tabima DM, Rodgers A, Hacker TA, Chesler NC, Zhang P, Murad R, Yuan JX, Shen Y, Chung WK, and McCulley DJ. Rescuing lung development through embryonic inhibition of histone acetylation. Sci Transl Med. 16(732): eadc8930, 2024. PMID: 38295182.
29. Tang H, Gupta A, Morrisroe S, Bao C, Schwantes-An TH, Gupta G, Liang S, Sun Y, Chu A, Luo A, Elangovan VR, Sangam S, Shi Y, Naidu S, Jheng J-R, Ciftci-Yilmaz S, Warfel N, Hecker L, Mitra S, Coleman A, Lutz KA, Pauciulo M, Lai Y-C, Javaheri A, Dharmakumar R, Wu W-H, Flaherty D, Karnes J, Breuils-Bonnet S, Boucherat O, Bonnet S, Yuan JX, Jacobson J, Duarte J, Nichols W, Garcia JGN, and Desai AA. Deficiency of the deubiquitinase, UCHL1, attenuates pulmonary hypertension. Circulation. In press, 2024.

Shen H, Gao Y,Ge D, Tan M, Yin Q, Wei T-YW, He F, Lee T-Y, Li Z, Chen Y, Yang Q, Liu Z, Li X, Chen Z, Yang Y. Zhang Z, Thistlethwaite PA, Wang J, Malhotra A, Yuan JX, Shyy JY-J, and Gong K. BRCC3 regulation of ALK2 in vascular smooth muscle cells: Implication in pulmonary hypertension. Circulation. In press, 2024. PMID: 38557054.