Career focus on pulmonary hypertension, systems biology, and the heart-lung-brain axis: I am a physician-scientist and cardiologist and serve as Director of the Vascular Medicine Institute (VMI). I also direct a research program and clinical center investigating mechanisms of pulmonary hypertension (PH), the systems biology of endothelial function, and heart-lung-brain axis communication in health and disease. At a translational level, PH is a vascular disease with enigmatic origins, increasing global significance, and unmet needs. Defining the complex molecular controls of PH and its systemic manifestations are crucial for designing a cure.
We seek to merge population-level molecular epidemiology with experimental biology and bioengineering to translate fundamental discoveries to clinical paradigm advances. Our program combines molecular and clinical molecular bioinformatics with unique rodent, human, and bioengineered vascular platforms to accelerate systems-wide discovery in vascular disease. My lab has defined genetic and acquired mechanisms of altered metabolism in PH, identifying iron-sulfur deficiencies and glutaminolysis as key disease drivers. This work serves as a basis for glutamine restriction as a dietary therapy for PH; clinical development of 18F-glutamine tracer for positron emission tomography (PET) diagnostic imaging; and testing therapeutic glutaminase inhibitors in humans. We have also identified regulatory processes of inflammation and mechanosensing in PH. We were the first to demonstrate the systems-level importance of non-coding RNAs in PH. More recently, we established a genetic and metabolic paradigm that links lysosomal biology and oxysterol generation to endothelial inflammation and PH. In doing so, we are defining metabolomic signatures identifying persons at-risk for PH mortality and developed new lysosomal therapies for vascular disease.
- PhD, University of California San Francisco, 2001
- MD, University of California San Francisco, 2003
- Residency, Internal Medicine, Brigham and Women's Hospital, 2005
- Clinical and Research Fellowship, Cardiology, Massachusetts General Hospital, 2009
- Research Fellow, Medicine, Harvard Medical School, 2009
Education & Training
Harvey LD, Alotaibi M, Tai YY, Tang Y, Kim HJ, Kelly NJ, Sun W, Woodcock CC, Arshad S, Culley MK, El Khoury W, Xie R, Al Aaraj Y, Zhao J, Hafeez N, Rao RJ, Jiang S, Negi V, Kirillova A, Perk D, Watson AM, St Croix CM, Stolz DB, Lee JY, Cheng MH, Zhang M, Detmer S, Guzman E, Manan RS, Saggar R, Haley KJ, Waxman AB, Okawa S, Schwantes-An TH, Pauciulo MW, Wang B, Webb A, Chauvet C, Anderson DG, Nichols WC, Desai AA, Lafyatis R, Nouraie SM, Wu H, McDonald JG, Cheng S, Bahar I, Bertero T, Benza RL, Jain M, CHAN SY. Lysosomal dysfunction and inflammatory sterol metabolism in pulmonary arterial hypertension. Science. 2025 Jan 24;387(6732):eadn7277. doi: 10.1126/science.adn7277. Epub 2025 Jan 24. PMID: 39847635.
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 Metab. 2024; 36(6): 1335-1350. PMID: 38701775. PMCID: PMC11152997.
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. Sci Transl Med. 2024. 16(729): eadd2029. DOI: 10.1126/scitranslmed.add2029. PMID: 38198571; PMCID: PMC10947529.
CHAN SY, Zhang YY, Hemann C, Mahoney CE, Zweier JL, Loscalzo J. MicroRNA-210 controls mitochondrial metabolism during hypoxia by repressing the iron-sulfur cluster assembly proteins ISCU1/2. Cell Metab. 2009 Oct;10(4):273-84. PMID: 19808020; PMCID: PMC2759401.
Baggish AL, Hale A, Weiner RB, Lewis GD, Systrom D, Wang F, Wang TJ, CHAN SY. Dynamic regulation of circulating microRNA during acute exhaustive exercise and sustained aerobic exercise training. J Physiol. 2011 Aug 15;589(Pt 16):3983-94. PMID: 21690193; PMCID: PMC3179997.
Parikh VN, Jin RC, Rabello S, Gulbahce N, White K, Hale A, Cottrill KA, Shaik RS, Waxman AB, Zhang YY, Maron BA, Hartner JC, Fujiwara Y, Orkin SH, Haley KJ, Barabási AL, Loscalzo J, CHAN SY. MicroRNA-21 integrates pathogenic signaling to control pulmonary hypertension: results of a network bioinformatics approach. Circulation. 2012 Mar 27;125(12):1520-32. PMID: 22371328; PMCID: PMC3353408.
Snow JW, Hale AE, Isaacs SK, Baggish AL, CHAN SY. Ineffective delivery of diet-derived microRNAs to recipient animal organisms. RNA Biol. 2013 Jul;10(7):1107-16. PMID: 23669076; PMCID: PMC3849158.
Baggish AL, Park J, Min PK, Isaacs S, Parker BA, Thompson PD, Troyanos C, D’Hemecourt P, Dyer S, Thiel M, Hale A, CHAN SY. Rapid upregulation and clearance of distinct circulating microRNAs after prolonged aerobic exercise. J Appl Physiol (1985). 2014 Mar 1;116(5):522-31. PMID: 24436293; PMCID: PMC3949215.
Bertero T, Lu Y, Annis S, Hale A, Bhat B, Saggar R, Saggar R, Wallace WD, Ross DJ, Vargas SO, Graham BB, Kumar R, Black SM, Fratz S, Fineman JR, West JD, Haley KJ, Waxman AB, Chau BN, Cottrill KA, CHAN SY. Systems-level regulation of microRNA networks by miR-130/301 promotes pulmonary hypertension. J Clin Invest. 2014 Aug;124(8):3514-28. Erratum in: J Clin Invest. 2022 May 16;132(10): PMID: 24960162; PMCID: PMC4109523.
Hale A, Lee C, Annis S, Min PK, Pande R, Creager MA, Julian CG, Moore LG, Mitsialis SA, Hwang SJ, Kourembanas S, CHAN SY. An Argonaute 2 switch regulates circulating miR-210 to coordinate hypoxic adaptation across cells. Biochim Biophys Acta. 2014 Nov;1843(11):2528-42. PMID: 24983771; PMCID: PMC4158026.
- Susan & Katherine McArthur-Radovsky Award, Brigham and Women's Hospital, 2011
- Jeremiah Stamler Distinguished Young Investigator Research Award, Northwestern University, 2011
- Cardiovascular Leadership Council Award, Brigham and Women's Hospital, 2013
- Prince Mansour Bin Bandar Al Saud Prize, Saudi Association for Pulmonary Hypertension, 2014
- Chair's Prize for Research Excellence, Brigham and Women's Hospital, 2015
- Elected Member, American Society for Clinical Investigation, 2016
- Inducted into the Association of University Cardiologists, 2023
Title: Hemostasis and Vascular Biology Research Institute -Risbano
Role: Co-Investigator
Funding Agency: Institute for Transfusion Medicine
Grant Number: RES
Start Year: 2018
End Year: 2028
Title: Hemostasis and Vascular Biology Research Institute
Role: Principal Investigator
Funding Agency: Vitalant Research Institute
Grant Number: RES
Start Year: 2020
End Year: 2028
