讲座题目: Proteotoxicity in Viral Cardiomyopathy

主讲人: Dr. Honglin Luo, Professor of Centre for Heart Lung Innovation, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.

主持人:李晓涛 教授

开始时间: 2015-5-29 14:00

讲座地址: 闵行生科院534报告厅

主办单位: 天美娱乐 科技处

 

报告人简介✊🏼：Honglin Luo is a Professor of Centre for Heart Lung Innovation, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada. Prof. Luo awarded her MD degree in 1986 in medicine from Chongqing Medical University, and in 1989 got her MSc degree in Hemodynamics, Biomedical Engineering from West China University of Medical Sciences, Chengdu, China. She was a postdoctoral fellow at Division of Cardiology and Department of Pathology, University of Washington from 1997 to 2000. In 2000 she joined University of British Columbia as Research Associate, then promoted to assistant professor and associate professor in 2003 and 2009. In July 2014, she was promoted to professor.

 

报告摘要：Enteroviruses are among the most prevalent etiological agents associated with viral myocarditis, an inflammatory disease of the myocardium. Viral myocarditis can lead to reduced cardiac function and the progression to dilated cardiomyopathy, which is a major cause of cardiovascular mortality worldwide, particularly in children. Our long-term research goal is to understand the molecular basis of viral myocarditis and the pathogenic mechanisms leading to cardiomyopathy. Protein degradation system plays a crucial role in maintenance of cellular homeostasis by removing protein aggregates and damaged organelles that are highly toxic to cells. Malfunction of this system are associated with human heart diseases. We previously demonstrated that enteroviral infection results in a massive accumulation of protein aggregates and damaged mitochondria, contributing significantly to viral pathogenesis. Recently, we demonstrated that the autophagic adapter proteins, p62/sequestosome 1 and Nbr1 (Neighbour of BRCA gene 1), which play a key role in protein quality control via targeting ubiquitin aggregates/organelles for autophagic degradation, are cleaved by virus-encoded proteases during enteroviral infection, resulting in impaired clearance of ubiquitin aggregates.  In addition, we found that transactive response DNA-binding protein-43 (TDP43) is translocated from the nucleus to the cytoplasm during enterovirus infection, followed by the cleavage mediated by viral protease, resulting in reduced solubility of TDP43 and increased formation of protein aggregates. TDP-43 is an RNA-binding protein that plays an essential role in regulating RNA metabolism at multiple levels. Cleavage and cytoplasmic aggregation of TDP-43 serves as a major molecular marker for amyotrophic lateral sclerosis and frontotemporal lobar degeneration and contributes significantly to disease progression. Taken together, our findings suggest novel mechanisms for the development of viral cardiomyopathy. Potential therapeutic application will be discussed.