Dr. Li Wang received his bachelor’s degree in Biological Science from Yunnan University and obtained his Master’s degree from the Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. Dr. Wang completed his Ph.D. and postdoctoral training at the Chinese University of Hong Kong. His Ph.D. research focused on metabolic disorders and atherosclerotic cardiovascular diseases. Dr. Wang joined the Department of Biomedical Sciences, the City University of Hong Kong as an assistant professor in 2021. Dr. Wang’s research interest lies in the early diagnosis of cardiovascular disease and drug discovery. His research on the role of endothelial YAP signaling in atherogenesis was published in Nature and he received the Higher Education Outstanding Scientific Research Output Award (first-class award) in 2019, Ministry of Education, China. He has so far co-authored 34 SCI-indexed publications in many prestigious journals including Nature, Circulation Research, Diabetes, Cardiovascular Research, PNAS, Pharmacology & Therapeutics, Arteriosclerosis, Thrombosis and Vascular Biology and Journal of the American Society of Nephrology.
Atherosclerotic plaque mainly develops at the branches, bifurcation, and curvature of vascular trees, where the vascular wall is subjected to disturbed blood flow. In this study, we investigate the role of YAP, a mechanical response gene, in disturbed shear forces-induced signal transduction and atherogenesis processes. Our results revealed that YAP is activated by disturbed blood flow while suppressed by unidirectional laminar shear forces. YAP activation promoted atherosclerosis through the JNK-inflammation pathway. Statins, the first-line drugs for atherosclerosis, could inhibit YAP activity, suggesting YAP could be a therapeutic target. To identify new YAP inhibitors for atherosclerosis treatment, we established a drug screening platform and identified several compounds that could inhibit YAP and suppress atherogenesis. Since YAP is a transcriptional factor activated at the early stages of atherosclerosis, we hypothesize that YAP-induced secretory proteins could be early markers for atherosclerosis. Candidate protein was identified to be a YAP-regulated atherosclerotic biomarker. The serum level of candidate protein is higher in atheroprone mice and correlates to plaque formation. Suppression of candidate protein could alleviate the high-cholesterol diet-induced atherogenesis, indicating candidate protein could be a biomarker and a therapeutic target for early-stage atherosclerosis.