Dr. Chan Appointed as New Director of the VMI

On behalf of Mark Gladwin, MD, Professor and Chair, Department of Medicine

It gives me great pleasure to announce the appointment of Dr. Stephen Chan, M.D., Ph.D., as the new Director of the Vascular Medicine Institute beginning January 2020. Steve’s appointment concludes an exhaustive search and thorough review of a highly talented pool of internal and external candidates by an engaged Search Committee.   We are indebted to the input and guidance of Dr. Darrell Triulzi who diligently served as Chair of the Search Committee.  The Committee and the School of Medicine and UPMC leadership all recognized and appreciated that Steve possesses the passion, acumen, and leadership skills to guide the VMI through a second decade of growth and success.

I personally wish to thank everyone who has partnered with me to build the VMI into a stable and mature research institute of 37 core faculty members, supported by eight centers, and generating more than $12 million in annual research revenue; we are grateful to Vitalant and the Hemophilia Society of Western Pennsylvania for creating a sustained foundation of support allowing the VMI to pursue exciting and innovative basic and translational research.

Steve, who is a tenured Professor in the Department of Medicine, will continue his role as Director of the Center for Pulmonary Vascular Biology and Disease as well as Associate Program Director for Research in the Cardiology fellowship program. Since arriving at the University of Pittsburgh in 2015, he has established an impressive research enterprise that spans basic to translational research in the field of pulmonary hypertension. Capitalizing on the emerging discipline of “network medicine” he employs bioinformatics and computational biology in a systems-wide discovery approach using genetically altered rodent models and human subjects to accelerate translational discovery in pulmonary vascular disease.

Steve is the Principal Investigator of multiple NIH R-level and U-level grants, was awarded an Established Investigator Award from the American Heart Association, has made high impact discoveries, and has nurtured entrepreneurial programs developing novel therapies for patients suffering from pulmonary hypertension. He has received a number of research awards from the American Heart Association, the American College of Cardiology, and Harvard Medical School, including the Lerner Scholarship, the Watkins Discovery Award, the Harris Family Research Prize, the Cardiovascular Leadership Council Award, the Chair’s Prize for Research Excellence, and the McArthur-Radovsky Research Scholarship. Steve was elected to the American Society of Clinical Investigation in 2016, currently serves on five journal editorial boards, is an at-large member of the American Heart Association 3CPR Council Leadership Committee and is a standing member of the Respiratory Integrative Biology and Translational Research NIH Study Section.

PH Patient Research Day 2019

PH Patient Research Day was held on May 7, 2019.

New Study Explains Gene Mutation’s Impact on Pulmonary Hypertension

Pulmonary hypertension (PH) is a deadly disease of the blood vessels of the lung that presents with shortness of breath, exercise intolerance and can progress to heart failure and death. PH in general affects more than 10 M Americans alone with much greater numbers worldwide. While there are some medications for specific types of PH, there is no treatment that prevents or reverses the disease and there is no cure. This stems largely from the fact that we know very little about true origins of the disease at the molecular level. But, if we could make progress in that regard, much more effective strategies could be developed to detect and treat this deadly disease.

Importantly, it has been known that mutations in a gene called BOLA3 (BolA Family Member 3) can lead to a syndrome that results in PH in affected individuals. Prior to our work, it was entirely unclear how BOLA3 deficiency can drive PH. BOLA3 is also known to control the metabolism of the amino acid glycine, an amino acid, or building block of proteins in the body, that is known to be elevated in PH but with unclear significance to this disease. Over the course of three years, using a combination of state of the art experimental strategies including study of rare cells from BOLA3 mutant patients and special human and animal disease models of PH, the Chan lab defined BOLA3 as a crucial regulator of glycine production from blood vessels in the lung and with consequent impact on PH development.

These results provide a molecular explanation for the puzzling clinical and genetic associations linking pulmonary hypertension with high glycine states, such as those driven by BOLA3 mutations. Based on these results, future work can now be envisioned to utilize glycine as a testable marker to diagnose PH, perhaps even early in the disease process. Furthermore, altering glycine metabolism or exogenous depletion of glycine could be explored as a therapeutic maneuver. Finally, this work support the growing likelihood that genetic testing of mutations that predispose to pulmonary hypertension could be instrumental in identifying the presumably large, but currently undefined, population of individuals at-risk for developing PH worldwide.

BOLA3 Deficiency Controls Endothelial Metabolism and Glycine Homeostasis in Pulmonary Hypertension

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 JE, Sugahara M, Kagiyama N, Satoh T, Zhang M, Feng N, Gorcsan Iii J, Vargas SO, Haley KJ, Kumar R, Graham BB, Langer R, Anderson DG, Wang B, Shiva S, Bertero T, Chan SY.

Circulation. 2019 Feb 14. doi: 10.1161/CIRCULATIONAHA.118.035889. [Epub ahead of print].   PMID: 30759996