Speaker

AFFILIATION:

UT Southwestern Medical Center, Dallas, TX, USA

POSITION TITLE:

Investigator, Howard Hughes Medical Institute
George L. MacGregor Distinguished Chair in Biomedical Science
Professor,

EDUCATION/TRAINING:

Fujian Normal University, Fuzhou, China      B.S.         1985                Biology
SUNY-Buffalo, Buffalo, NY                                Ph.D.       1991                Biochemistry
Salk Institute, San Diego, CA                         Postdoc       1992                Molecular Biology

HONORS:

RESEARCH INTERESTS:

The goal of Dr. Chen’s research is to elucidate the biochemical mechanism underlying innate immunity and cell signaling. In the last 20 years since the laboratory at UT Southwestern was established, Dr.Chen’s research team has made several important discoveries that contribute to the current understanding of innate immune signaling. 1) The discovery of a key role of ubiquitination in the activation of protein kinases in the NF-kB signaling cascade. Importantly, we found that TRAF6 is a ubiquitin E3 ligase that catalyzes K63 polyubiquitination, which activates TAK1 and IKK through a proteasome-independent mechanism. 2) They discovered MAVS, a mitochondrial membrane protein that plays a key role in the RIG-I antiviral innate immunity pathway. 3) They reconstituted the entire RIG-I signaling pathway in a cell free system and uncovered an important role of unanchored K63 polyubiquitin chain in activating RIG-I. 4) They discovered a prion-like property of MAVS and demonstrated that prion-like aggregation of MAVS activates and propagates antiviral signaling cascade. 5) They discovered a new enzyme called cyclic GMP-AMP synthase (cGAS), which functions as the cytosolic DNA sensor that triggers the production of type-I interferons and other immune regulatory molecules. Upon binding to DNA, cGAS is activated to catalyze the synthesis of a unique isomer of cyclic GMP-AMP (2’3’-cGAMP). This cGAMP molecule then functions as a second messenger that binds to and activates the adaptor protein STING, which in turn activates a signaling cascade to induce interferons. 6) They recently discovered that the cGAS-STING pathway is essential for intrinsic antitumor immunity and the therapeutic effects of immune checkpoint blockade in mouse tumor models. They also demonstrated that cGAS is essential for cellular senescence

 

PUBLICATIONS:

List of published work in Google Scholar:
https://scholar.google.com/citations?hl=zh-TW&user=MUow0FwAAAAJ