Dr. X-J. Wang received his Bachelor of Medicine (M.D. equivalent; 1985) and Master of Medicine (1988) from Wuhan University College of Medicine (Wuhan, Hubei, China) where he had risen to the rank of Associate Professor before relocated to the US in 1994. After earning his Ph.D. (1998) from University of South Dakota (USD) School of Medicine (Vermillion, SD, USA), Dr. Wang pursued his postdoctoral training at Cincinnati Children’s Hospital Medical Center (Cincinnati, OH, USA). He was recruited back to USD School of Medicine as an Assistant Professor in 2001, promoted to Associate Professor in 2005, tenured in 2006, and reappointed to full Professor in 2006.
Dr. Wang’s research has been primarily on the heart, with recent 20 years focusing on protein quality control and degradation (PQCD) and proteotoxicity, especially the ubiquitin-proteasome system (UPS) and autophagy in cardiac pathophysiology. Funded primarily by the NIH and the American Heart Association (AHA), Dr. Wang’s laboratory has been a leading force for studying the role of PQCD dysfunction in cardiac pathogenesis. His lab provided the first demonstration that misfolded proteins impair UPS performance in intact animals, discovered that overexpression of PA28alpha can enhance proteasomal removal of misfolded proteins, developed the first animal model of proteasome gain of function, and demonstrated its benefit in the removal of misfolded proteins and protection against proteinopathy, thereby providing the first demonstration in any organs (or any disease for that matter) the necessity of proteasome functional insufficiency in pathogenesis. His lab also established the first mouse model with cardiomyocyte-restricted proteasome inhibition and showed that cardiac proteasome inhibition exacerbates myocardial ischemia/reperfusion (I/R) injury and promotes progression of pressure overloaded hearts to heart failure. More recently, his lab has demonstrated that inadequate coupling between ubiquitination and proteasomal degradation contributes to I/R injury. The COP9 signalosome (CSN) was purported to regulate the UPS. Work from the Wang lab uncovers that CSN8/CSN is required for not only cardiac UPS functioning but also autophagosome-lysosome fusion, thereby demonstrating for the first time that the CSN plays an important role in regulating macroautophagy. Having established the importance of these mechanisms in heart disease, a major current focus is how proteasome function is regulated. In this regard, Dr. Wang was the first to discover that protein kinase G positively regulates proteasome proteolytic function. This opens the exciting possibility of pharmacological enhancement of cardiac proteasome function using existing FDA-approved agents (e.g., sildenafil).
Dr. Wang has received a number of recognitions and awards, including Young Investigator Awards from the International Society for Heart Research-North American Section (ISHR-NAS) and the Heart Failure Society of America (HFSA), AHA Established Investigator Award (EIA), and the USD President’s Award for Research Excellence in the Established Faculty category. He has served on grant review panels for multiple funding agencies, such as NIH, AHA, China National Nature Science Foundation, Singapore Medical Research Council, Israel Science Foundation, etc. He served/serves on a number of editorial boards, such as Circ Res, Am J Physiol-Heart, and Am J Cardiovasc Dis. He authored >140 peer-reviewed full-length publications in well-respected journals, including J Clin Invest, Circulation, Circ Res, JACC, Cell Rep, Cell Death Diff, Cell Res, etc. Dr. Wang’s work has helped establish the theory that PQCD inadequacy contributes to maladaptive cardiac remodeling and heart failure, identifying potentially a novel therapeutic strategy to fight heart disease.