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Immune and autoimmune responses to cytosolic DNA
Zhijian ‘James’ Chen
Howard Hughes Medical Institute; Department of Molecular Biology, University of Texas
Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9148
The presence of DNA and aberrant RNA in the cytoplasm is a danger signal that alerts the host
immune system to eliminate microbial infections and malignant cells, but inappropriate activation
of these pathways can also lead to autoimmune diseases such as lupus. My talk will focus on our
recent discovery of cyclic GMP-AMP (cGAMP) synthase (cGAS) as an innate immune sensor for
cytosolic DNA. Upon binding to DNA, cGAS catalyzes the synthesis of cGAMP, which then
functions as a second messenger to bind and activate the adaptor protein STING to induce type-I
interferons and other inflammatory cytokines. I will report our recent progress towards dissecting
the biochemical mechanism of signal transduction in the cGAS pathway. I will also discuss the roles
of the cGAS pathway in immune defense and autoimmunity.