Winner of 2016 FAOBMB Award for Research Excellence: Professor Feng Shao (China)
Dr. Feng Shao is a renowned biochemist internationally and also a highly interdisciplinary scientist working on important questions in the field of pathogen-host interaction. He has been a member of the Chinese Biochemistry and Molecular Biology (CSBMB) for 5 years.
Dr. Shao’s research has identified several cytosolic innate immune pattern recognition receptors (PRRs) that recognize invading bacteria and activate inflammatory caspases (caspase-1/4/5/11)-mediated pyroptotic cell death. Among those are the NAIP family of PRRs for bacterial flagellin and a toxin-injection type III secretion apparatus. Pyrin, encoded by the familial Mediterranean fever disease gene, senses various bacterial toxins that modify and inactivate host Rho GTPases, revealing how the innate immune system distinguishes pathogens from non-pathogenic microbes. Most remarkably, he has also discovered that caspase-4/5 in human and caspase-11 in mice are intracellular receptors for LPS, a ground-breaking discovery that explains why blocking the extracellular LPS receptor (TLR4) failed to halt sepsis in humans. He has further identified a novel Gasdermin D (GSDMD) protein whose cleavage by inflammatory caspases triggers pyroptosis and strong inflammatory responses, which clarifies an important aspect concerning cell death and inflammation that has been mysterious for more than 20 years. His most recent work also demonstrates that GSDMD and also the large Gasdermin family of proteins are all pyroptosis-inducing factors with membrane-disrupting pore-forming activity. These seminal discoveries have established a biochemical framework for understanding cytosolic anti-bacterial immunity including the sensing and execution mechanisms. Identification of the intracellular LPS receptor and its downstream mechanism (GSDMD) provides a novel and highly promising target for developing anti-sepsis drugs. Discovery of the pore-forming activity of the Gasdermin family not only re-defines the concept of pyroptosis but also opens a new area in cell death and inflammation research.
The other part of Dr. Shao’s work has revealed how bacterial pathogens employ novel enzymatic reactions to inactivate host immune defense by unprecedented posttranslational modifications. Discoveries made by his laboratory include: the phosphothreonine lyase effector family that irreversibly “dephosphorylates” host MAP kinase; the ubiquitin/NEDD8 deamidase virulence factors interrupting host ubiquitin system; bacteria-catalyzed cysteine methylation modification of host TAB2/3 proteins that results in blocking of the NF-kB signaling; and arginine GlcNAcylation of host death-domain proteins in inhibiting host cell death and suppressing inflammation in mice. His research has also identified a novel RabGAP activity in bacterial virulence factors VirA (Shigella) and EspG (pathogenic E. coli), which plays important roles in pathogenesis. These novel virulence mechanisms and concepts have been a driving force in bacterial pathogen-host interaction research, and also provide ways to design new therapeutic strategies or vaccines for those hard-to-treat bacterial diseases.
Dr. Shao, as the corresponding author, has published more than 30 research articles in major scientific journals, including 10 in Nature, Science and Cell. His work is highly cited (> 5,000 times) and widely recognized internationally. He serves as an editor for eLife and Cellular Microbiology, and is on the editorial board of several journals including Journal of Molecular Biology and Journal of Bacteriology. As a result of his outstanding accomplishments and contributions, Dr. Shao has earned numerous prestigious awards including the Howard Hughes Medical Institute (HHMI) International Early Career Scientist and the Irving Sigal Young Investigator Award from the Protein Society in US. He was elected as a member of the Chinese Academy of Science and an associate member of the European Molecular Biology Organization (EMBO) at the age of 42. Very recently, he was also elected to be a Fellow of American Academy of Microbiology. Dr. Shao is a founding member of the then-newly established National Institute of Biological Sciences (NIBS), Beijing and now functions as the Deputy Director for Research at the institute.