Education & Training
- B.S. Massachusetts Institute of Technology, Biology-1995
- Ph.D., University of California, Biomedical Sciences-2001
- M.D., University of Callifornia, Medicine-2003
Research Interest Summary
Research Categories
Research Interests
I am a physician-scientist and cardiologist who leads a basic and translational research program and clinical center investigating the mechanisms of pulmonary hypertension (PH) and endothelial biology. More recently, our lab has been studying the mechanisms by which the heart-lung-brain axis communicates in health and disease. To do so, we use computational theory to study gene network architecture and couple these insights with unique experimental reagents derived from genetically altered rodent and human subjects. By combining in silico network biology approaches with in vivo mechanistic discovery, our lab has defined the systems-level functions of non-coding RNAs and downstream pathways controlling metabolism, mechanosignaling, and inflammation as root causes of vascular disease and pulmonary hypertension (PH). These findings have led to new methods implemented to identify persons at-risk for PH and to the development of new molecular therapies targeting these pathogenic causes. This work is also the cornerstone of evolving applications of network theory to the discovery of RNA-based origins of human diseases, in general.
Representative Publications
Bertero T, Oldham WM, Cottrill KA, Pisano S, Vanderpool RR, Yu Q, Zhao J, Tai Y, Tang Y, Zhang YY, Rehman S, Sugahara M, Qi Z, Gorcsan III J, Vargas SO, Saggar R, Saggar R, Wallace WD, Ross DJ, Haley KJ, Waxman AB, Parikh VN, De Marco T, Hsue PY, Morris A, Simon MA, Norris KA, Gaggiol, C, Loscalzo J, Fessel J, Chan SY (Senior Author). Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension. Journal of Clinical Investigation. 2016; 126(9):3313-35. PMID: 28548520; PMCID: PMC5004943.
Yu Q, Tai YY, Tang Y, Zhao J, Negi V, Culley MK, Pilli J, Sun W, Brugger K, Mayr J, Saggar R, Saggar R, Wallace WD, Ross DJ, Waxman AB, Wendell SG, Mullett SJ, Sembrat J, Rojas M, Khan OF, Dahlman J, Sugahara M, Kagiyama N, Satoh T, Zhang M, Feng N, Gorcsan J, Vargas SO, Haley KJ, Kumar R, Graham BB, Langer R, Anderson DG, Wang B, Shiva S, Bertero T, Chan SY (Senior Author). BOLA3 deficiency controls endothelial metabolism and glycine homeostasis in pulmonary hypertension. Circulation. 2019; 139(19):2238-2255. PMID: 30759996; PMCID: PMC6519484.
Zhao J, Florentin J, Tai YY, Torrino, S, Ohayon L, Brzoska T, Tang Y, Yang J, Negi V, Woodcock CC, Risbano MG, Nouraie SM, Sundd P, Bertero T, Dutta P, Chan SY (Senior Author). Long range endocrine delivery of circulating miR-210 to endothelium promotes pulmonary hypertension. Circulation Research. 2020; 127(5):677-692. PMID: 32493166; PMCID: PMC7429300.
Culley MK, Zhao J, Tai YY, Tang Y, Perk D, Negi V, Yu Q, Woodcock C-SC, Handen A, Speyer G, Kim S, Lai Y-C, Satoh T, Watson A, Al Aaraj Y, Sembrat J, Rojas M, Goncharov D, Goncharova EA, Khan OF, Anderson DG, Dahlman JE, Gurkar A, Lafyatis R, Fayyaz AU, Redfield MM, Gladwin MT, Rabinovitch M, Gu M, Bertero T, Chan SY (Senior Author). Frataxin deficiency promotes endothelial senescence in pulmonary hypertension. Journal of Clinical Investigation. 2021; 131(11):e136459. PMID: 33905372; PMCID: PMC8159699.
Negi V, Yang J, Speyer G, Pulgarin A, Handen A, Zhao J, Tai YY, Tang Y, Culley MK, Yu Q, Forsythe P, Gorelova A, Watson AM, Al Aaraj Y, Satoh T, Sharifi-Sanjani M, Rajaratnam A, Sembrat J, Provencher S, Yin X, Vargas SO, Rojas M, Bonnet S, Torrino S, Wagner BK, Schreiber SL, Dai M, Bertero T, Al Ghouleh I*, Kim S*, Chan SY (*Co-Senior Authors). Computational repurposing of therapeutic small molecules from cancer to pulmonary hypertension. Science Advances. 2021; 7:eabh3794. PMID: 34669463; PMCID: PMC8528428.
Hafeez N, Kirillova A, Yue Y, Rao R, Kelly N, El Khoury W, Al Aaraj Y, Tai Y-Y, Handen A, Tang Y, Jiang D, Wu T, Zhang Y, McNamara D, Kudryashova T, Goncharova EA, Goncharov D, Betero T, Nouraie M, Li G, Sun W*, Chan SY* (*Co-Senior Authors). SNP rs9277336 Controls the ACTN4-HLA-DPA1 Axis and Pulmonary Endothelial Pathophenotypes in Pulmonary Arterial Hypertension. Journal of the American Heart Association. 2023; 12(7):e027894. PMID: 36974749. PMCID: PMC10122886.
Tai Y-Y, Yu Q, Tang Y, Sun W, Kelly NJ, Okawa S, Zhao J, Schwantes-An T-H, Lacoux C, Torrino S, Al Aaraj Y, El Khoury W, Negi V, Liu M, Corey CG, Belmonte F, Vargas SO, Schwartz B, Bhat B, Chau BN, Karnes JH, Satoh T, Barndt RJ, Wu H, Parikh VN, Wang J, Zhang Y, McNamara D, Li G, Speyer G, Wang B, Shiva S, Kaufman B, Kim S, Gomez D, Mari B, Cho MH, Bouiez A, Pauciulo MW, Southgate L, Trembath RC, Sitbon O, Humbert M, Graf S, Morrell NW, Rhodes CJ, Wilkins MR, Nouraie M, Nichols WC, Desai AA, Bertero T, Chan SY (Senior Author). Allele-specific control of rodent and human lncRNA KMT2E-AS1 promotes hypoxic endothelial pathology in pulmonary hypertension. Science Translational Medicine. 2024. 16(729):eadd2029. DOI:10.1126/scitranslmed.add2029. PMID: 38198571. PMCID: PMC10947529.
Rachedi NS, Tang Y, Tai YY, Zhao J, Chauvet C, Grynblat J, Akoumia KF, Estephan L, Torrino S, Sbai C, Ait-Mouffok A, Latoche JD, Al Aaraj Y, Brau F, Abélanet S, Clavel S, Zhang Y, Guillermier C, Kumar NVG, Tavakoli S, Mercier O, Risbano MG, Yao Z-K, Yang G, Ouerfelli O, Lewis JS, Montani D, Humbert M, Steinhauser ML, Anderson C, Oldham WM, Perros F, Bertero T*, Chan SY* (*Co-Senior Authors). Dietary intake and glutamine-serine metabolism control pathologic vascular stiffness. Cell Metabolism. 2024. 36(6): 1335-1350. PMID: 38701775. PMCID: PMC11152997.