BME Distinguished Lecturer (ZOOM): Shu Chien, UC San Diego

Epigenetic Regulation of Vascular Mechanotransduction

Abstract: Vascular endothelial cells (ECs) play significant roles in regulating circulatory homeostasis. Shear stress resulting from circulatory flow modulates EC functions by mechanotransduction involving mechano-sensors, signaling pathways, and gene and protein expressions. Sustained shear stress with a clear direction (pulsatile shear stress, PS, in the straight arteries) down-regulates pro-inflammatory and proliferative pathways. Shear stress without definitive direction (disturbed or oscillatory flow, OS, at branches and curvatures) causes sustained signaling of pro-inflammatory and proliferative pathways. These flow patterns cause differential epigenetic responses, including microRNA (miR), histone modifications and DNA methylation, as well as long non-coding RNA. The detrimental effects of OS on miRs, histone modification and DNA hypermethylation are found in disturbed flow areas of rat arteries in vivo. These experimental studies on epigenetic mechanisms provide new insights on the fine tuning of EC gene regulation in response to differential flows in health and disease.

Bio: Shu Chien received a medical degree from National Taiwan University and doctorate in physiology from Columbia. In 1988, he joined UC San Diego and founded the Department of Bioengineering. He is a university professor emeritus of bioengineering and medicine. His research emphases are effects of mechanotransduction and genetic/epigenetic regulation in relation to atherogenesis. Chien is a member of the U.S. National Academies of Engineering, Medicine and Sciences, and also the American Academy of Arts and Sciences, National Academy of Inventors, Academia Sinica and Chinese Academy of Sciences. He received National Medal of Science from former President Barack Obama.