Dr. Dongyang Jiang, Research Professor

School of Medicine, Tongji University, Shanghai, China

Biography

Dr. Dongyang Jiang is a research professor at Department of Cardiology, Pan-vascular Research Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine. She earned her bachelor's (basic medical science) and doctoral (immunology) degrees at Peking University and then joined Tongji University in 2014. She is the principal investigator for general and youth projects of the National Natural Science Foundation of China, a general project of the China Postdoctoral Science Foundation and a project of the Shanghai Science and Technology Committee. She also serves as the member of the Chinese Society of Immunology (CSI), the Chinese Society of Biochemistry and Molecular Biology (CSBMB), and the American Heart Association (AHA). Her research focuses on the molecular mechanisms of dynamic regulation of the endothelial barrier, exploring the roles in cardiovascular diseases such as atherosclerosis, abdominal aortic aneurysm, and pulmonary arterial hypertension. Her team recently discovered a novel mechanosensitive molecule in atherosclerosis, PHACTR1. She has published 15 research articles in scholarly journals including ATVB, Hypertension, Cancer Letters, and the British Journal of Pharmacology. She has been honored with awards such as AHA Young Scientist Travel Award and CSBMB Young Scientist Award.

Topic

Multifaceted Roles of PHACTR1 in Atherosclerosis

Abstract

Although compelling evidence suggested the strong association of phosphatase and actin regulator 1 (PHACTR1) with atherosclerosis, the biological function of PHACTR1 remains poorly understood. Macrophage PHACTR1 was demonstrated to be protective by facilitating efferocytosis and attenuating atherosclerotic plaque necrosis. Our group identified the pro-atherosclerotic effect of endothelial PHACTR1, contrary to macrophage PHACTR1. Global or endothelial cell (EC)-specific PHACTR1 deficiency significantly inhibited atherosclerosis in regions of disturbed flow. PHACTR1 was enriched in ECs and located in the nucleus of disturbed flow area but shuttled to cytoplasm under laminar flow in vitro. RNA-seq using EC-enriched RNA showed that Phactr1 depletion affected vascular function and peroxisome proliferator-activated receptor gamma (PPARγ) was the top transcription factor regulating differentially expressed genes. PHACTR1 functioned as a PPARγ transcriptional corepressor by binding to PPARγ through the corepressor motifs. PPARγ activation protects against atherosclerosis by inhibiting endothelial activation. Consistently, PHACTR1 deficiency remarkably reduced endothelial activation. PPARγ antagonist GW9662 abolished the effects of Phactr1 knockout on EC activation and atherosclerosis. Targeting the interaction of PHACTR1 and PPARγ will provide a promising therapeutic strategy for atherosclerosis.