Xuewu Zhang, professor of pharmacology and biophysics at UT Southwestern Medical Center, will give an Apex Lecture on Monday, March 4, at 4:15 p.m. CT in 1220 MRBIII. A reception will immediately follow the lecture in the MRBIII atrium.
His talk, “Structures of the Innate Immunity Adaptor STING: From Mechanisms to Potential Therapeutics,” is co-sponsored by the Department of Pharmacology.
Xuewu Zhang earned his graduate degree from the Albert Einstein College of Medicine under renowned immunologist Stanley Nathenson and served as a postdoctoral associate in the lab of John Kuriyan at the University of California, Berkeley. He is currently a professor in the Department of Pharmacology at UT Southwestern Medical Center.
The general interest of the Zhang lab is to understand mechanisms for the regulation of signaling proteins through intra- and inter-molecular interactions. A major focus is on receptor-mediated signaling pathways involved in neuron development and axonal guidance, and more recently those involved in the innate immunity. Zhang uses biochemistry, X-ray crystallography, cryo-EM and cell biological approaches to seek understanding of the regulatory mechanisms at the atomic level.
“Dr. Zhang is a pioneering structural biologist,” said Ege Kavalali, Vanderbilt Department of Pharmacology Professor & Chair, “with numerous groundbreaking contributions to our current understanding of signal transduction mechanisms. In particular, he provided seminal insight into how extracellular ligands interact with membrane receptors and direct cellular signaling.”
Zhang has shown that the plexin intracellular region has GTPase activating protein (GAP) activity specific to the Ras homolog Rap, and this activity is critical for its signaling. More recently, Zhang and collaborators have determined the cryo-EM structures of full-length STING and its complex with TBK1. Their structures of STING and the STING/TBK1 complex provide detailed molecular views of full-length STING in both the inactive and cGAMP-bound active states, as well as its interaction with TBK1, allowing us to propose a complete model of the activation of STING by cGAMP, and the subsequent recruitment and activation of TBK1.
About the Apex Lecture Series
There are major inflection points in biomedical discovery that create new fields, new ideas, and new opportunities to impact human health. To engage with global researchers contributing to these inflection points, the Vanderbilt School of Medicine Basic Sciences launched the Apex Lecture Series in 2023. This school-wide seminar series brings scientists who are influencing the trajectory of their fields to engage with our scientific community on campus.
Lecture abstract
STING is a critical innate immunity adaptor protein in the cytosolic DNA-sensing pathway. Activation of STING by the second messenger cGAMP triggers a host of immune responses, including interferon production, autophagy, and inflammation. STING-mediated immunity is not only essential for responses to bacterial and viral infection, but also plays an important role in tumor suppression. STING therefore has been extensively studied and exploited for therapeutic purposes. In this seminar, I will present our recent cryo-EM structures of STING in various states and STING bound to several small, drug-like molecules that have potential to be developed into therapeutics. The structural analyses provide key insights into the fundamental regulatory mechanisms of STING and guide drug development.