Life Sciences
Feng Shao
Discovery of the cytosolic immune receptor for bacterial LPS and its downstream pyroptosis execution protein GSDMD
Abstract:These studies for the first time identify and characterize three cytosolic innate immune receptors or sensors for major bacterial molecular pattern molecules, as well as their downstream pyroptosis-execution protein GSDMD. The three immune receptors (NAIPs, Pyrin and caspase-11/4/5) activate a form of programmed cell death called pyroptosis, but the underlying mechanism was unknown for more than 20 years. Indeed, the nature of pyroptotic cell death was not clear and it was long regarded as a special form of apoptosis. The work has now solved the mystery by identifying the novel gasdermin-D (GSDMD) protein with a novel membrane-disrupting pore-forming activity. With the identification of GSDMD, the nature of pyroptosis is now well established and agreed as an immunogenic necrotic cell death. Formation of the GSDMD membrane pores is also required for extracellular secretion of caspase-1-processed IL-1, solving a longstanding mystery about noncanonical secretion of inflammatory cytokines in immunology research. As the intracellular LPS-sensing pathway is required for septic shock, identification of GSDMD brings a novel concept that excessive and systemic pyroptosis is the determinant for sepsis, providing a novel route for drug development. Moreover, the gasdermin family of protein is not only the core execution protein and molecular marker for pyroptotic cell death, but also represents the first type of pore-forming protein present in the cytosol of mammalian cells.
Awardee:Dr. Feng Shao was born in Huaian, Suzhou Province in 1972. He is a member of the Chinese Academy of Sciences and the German National Academy of Sciences Leopoldina, an associate member of EMBO, and a fellow of American Academy of Microbiology. He is an investigator and deputy director at National Institute of Biological Sciences (NIBS), Beijing, China. He was a chemistry undergraduate of Peking University (1991-1996) and obtained his PhD with Dr. Jack E. Dixon from University of Michigan in 2003. Prior to returning to China in 2005 to assume an assistant investigator at NIBS, he was a Damon Runyon Postdoc Research Fellow at Harvard Medical School. 
Dr. Shao’s research lies at the interface between bacterial pathogen and host inflammation. He identified cytosolic pattern recognition receptors for major bacterial molecules. He also identified gasdermin-D (GSDMD) whose cleavage by caspase-1/4/5/11 determines pyroptosis, a proinflammatory cell death critical for septic shock and many other diseases. His research further establishes the gasdermin family of pore-forming proteins, re-defining pyroptosis as gasdermin-mediated programmed necrosis. Among the family, GSDME is activated by caspase-3, which contributes to the toxicity of chemotherapy drugs.
Dr. Shao‘s work has been recognized by numerous awards including the Future Science Prize, Qiu Shi Outstanding Scientist Award, HHMI International Early Career Award and the Protein Society Irving Sigal Young Investigator Award. The work on pyroptosis was selected by journal Nature Reviews Immunology as one of the “Immune discovery aplenty at twenty”.