Hosted
Sessions 3：Life Sciences
Feng Shao
Character introduction
Dr. Feng Shao is an investigator and deputy director at National Institute of Biological Sciences (NIBS), Beijing. He was a chemistry undergraduate of Peking University and obtained his PhD from University of Michigan in 2003. Before becoming a faculty member at NIBS in 2005, he was a Damon Runyon Postdoc 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, including caspase-11/4/5 for LPS and ALPK1 for ADP-heptose, a precursor for LPS biosynthesis. 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. 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.
Topic: Pyroptosis: from Innate Immunity to Cancer
Abstract Pyroptosis, originally known to be activated by caspase-1/4/5/11, is critical for immune defenses and development of many immunological diseases. While caspase-1 is downstream of the inflammasome complex that senses infections, caspase-11 and its human counterparts caspase-4/5 serve as cytosolic receptors for bacterial lipopolysaccharide (LPS) to activate pyroptosis-mediated immune defenses. These caspases cleave Gasdermin D (GSDMD) to release the autoinhibition on its Gasdermin-N domain that executes pyroptosis via an intrinsic membrane pore-forming activity. Gsdmd-/- mice are susceptible to various bacterial infections but also resistant to LPS-induced septic shock. GSDMD belongs to a large Gasdermin family sharing the autoinhibited pore-forming domain. Another family member GSDME harbors a caspase-3-recognition motif also in the middle linker region and can switch caspase-3-induced apoptosis to pyroptosis. Similarly, caspase-3 cleavage releases the pore-forming domain of GSDME, and the resulting pyroptosis also occurs in cells treated with DNA-damaging chemotherapy drugs. GSDME is silenced in most cancer cells but expressed in normal tissues. GSDME-positive cells from normal human tissues undergo caspase-3-dependent pyroptosis in response to chemotherapy drugs. Knockdown of GSDME expression in these primary cells converts the death from pyroptosis to apoptosis. Importantly, Gsdme-/- mice are protected from chemotherapy drug-induced tissue damage and weight loss. These findings define pyroptosis as Gasdermin-mediated programmed necrotic cell death that shall have important functions in a wide spectrum of biological and pathological processes.
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