Stephen Y. Chan, MD, PhD

  • Director, Center for Pulmonary Vascular Biology and Medicine
  • Associate Professor of Medicine, Division of Cardiology, Department of Medicine

Education & Training

  • Graduate School – University of California, San Francisco – PhD
  • Medical School – University of California, San Francisco – MD
  • Internship – Brigham and Women’s Hospital – Internal Medicine
  • Residency – Brigham and Women’s Hospital – Internal Medicine
  • Fellowship – Massachusetts General Hospital - Cardiology

Research Grants

NIH Grants:  R01, K08, R43, UH2

Research Summary

We are a basic science and translational research group studying the molecular mechanisms of pulmonary vascular disease and pulmonary hypertension (PH) – an example of an enigmatic disease where reductionistic studies have primarily focused on end-stage molecular effectors. To capitalize on the emerging discipline of “network medicine,” our research utilizes a combination of network-based bioinformatics with unique experimental reagents derived from genetically altered rodent and human subjects to accelerate systems-wide discovery in PH. Our published findings were among the first to identify the systems-level functions of microRNAs (miRNAs), which are small, non-coding RNAs that negatively regulate gene expression, as a root cause of PH. Our lab developed novel in silico approaches to analyze gene network architecture coupled with in vivo experimentation. The results now offer methods to identify persons at-risk for PH and develop therapeutic RNA targets. This work is the cornerstone of our evolving applications of network theory to the discovery of RNA-based origins of human diseases.

Representative Publications

  1. Stearman RS, Bui QM, Speyer G, Handen A, Cornelius AR, Graham BB, Kim S, Mickler EA, Tuder RM, Chan SY, Geraci MW. Systems Analysis of the Human Pulmonary Arterial Hypertension Lung Transcriptome. American Journal of Respiratory Cell and Molecular Biology. 2018. In press.
  2. Culley MK, Chan SY. Mitochondrial metabolism in pulmonary hypertension: beyond mountains there are mountains. J Clin Invest. 2018 Aug 31;128(9):3704-3715. doi: 10.1172/JCI120847. PubMed PMID: 30080181; PubMed Central PMCID: PMC6118596.
  3. Florentin J, Coppin E, Vasamsetti SB, Zhao J, Tai YY, Tang Y, Zhang Y, Watson A, Sembrat J, Rojas M, Vargas SO, Chan SY*, Dutta P* (Co-Corresponding Authors). Inflammatory Macrophage Expansion in Pulmonary Hypertension Depends upon Mobilization of Blood-Borne Monocytes. J Immunol. 2018 May 15;200(10):3612-3625. PMCID: PMC5940510.
  4. Thomas Bertero, William M. Oldham, Katherine A. Cottrill, Sabrina Pisano, Rebecca R. Vanderpool, Qiujun Yu, Jingsi Zhao, Yiyin Tai, Ying Tang, Ying-Yi Zhang, Sofiya Rehman, Masataka Sugahara, Zhi Qi, John Gorcsan III, Sara O. Vargas, Rajan Saggar, Rajeev Saggar, W. Dean Wallace, David J. Ross, Kathleen J. Haley, Aaron B. Waxman, Victoria N. Parikh, Teresa De Marco, Priscilla Y. Hsue, Alison Morris, Marc A. Simon, Karen A. Norris, Cedric Gaggioli, Joseph Loscalzo, Joshua Fessel, STEPHEN Y. CHAN. Vascular stiffness drives metabolic alterations in pulmonary hypertension.  The Journal of Clinical Investigation.  126(9):3313-35 (2016).
  5. Bertero T, Cottrill KA, Lu Y, Haeger CM, Dieffenbach P, Annis S, Hale A, Bhat B, Kaimal V, Zhang YY, Graham BB, Kumar R, Saggar R, Saggar R, Wallace WD, Ross DJ, Black SM, Fratz S, Fineman JR, Vargas SO, Haley KJ, Waxman AB, Chau BN, Fredenburgh LE, STEPHEN Y. CHAN. Matrix remodeling promotes pulmonary hypertension through feedback mechanoactivation of the YAP/TAZ-miR-130/301 circuit. Cell Reports 13(5):1016-1032 (2015).
  6. Kevin White, Yu Lu, Sofia Annis, Andrew E. Hale, B. Nelson Chau, James E. Dahlman, Craig Hemann, Alexander Opotowsky, Sara O. Vargas, Rosas I, Mark A. Perrella, Juan C. Osorio, Kathleen J. Haley, Brian B. Graham, Rahul Kumar, Rajan Saggar, Rajeev Saggar, W. Dean Wallace, David J. Ross, Omar F. Khan, Andrew Bader, Bernadette R. Gochuico, Majed Matar, Kevin Polach, Nicolai M. Johannessen, Daniel G. Anderson, Robert Langer, Jay L. Zweier, Laurence A. Bindoff, David Systrom, Aaron B. Waxman, Richard C. Jin, STEPHEN Y. CHAN. Genetic and hypoxic alterations of the microRNA-210-ISCU1/2 axis promote iron-sulfur deficiency and pulmonary hypertension. EMBO Molecular Medicine. 7:695-713 (2015).
  7. 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. Journal of Clinical Investigation. 2014; 124(8):3514-3528. PMCID: PMC4109523.

NCBI bibliography