Investigator, NIBS, Beijing, China
|1996||B.S. Applied Chemistry, Peking University, Beijing, China|
|1999||M.S. Molecular Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China|
|2003||Ph.D. Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI, USA|
|2012-present||Investigator, National Institute of Biological Sciences, Beijing, China|
|2009-2012||Associate Investigator, National Institute of Biological Sciences, Beijing, China|
|2005-2009||Assistant Investigator, National Institute of Biological Sciences, Beijing, China|
|2004-2005||Damon Runyon Postdoctoral Research Fellow, Harvard Medical School, Boston, USA|
|2003-2004||Postdoctoral Research Fellow, School of Medicine, University of California, San Diego, USA|
Dr. Feng Shao's laboratory is interested in studying molecular mechanisms of bacterial infection and host innate immunity defense. Bacterial pathogens use specialized secretion systems such as type III/IV secretion system to inject effector proteins into host cells, serving as a key and universal virulence mechanism. The effectors usually harbor a unique and potent activity that modulates the function of key signaling molecules in the host, and this plays a critical role in bacterial survival and systemic infections. Using pathogens such as Shigella, Salmonella, Enteropathogenic E. coli (EPEC), Legionella and Burkholderia as the model, we are working to discover and reveal some novel and common biochemical mechanisms utilized by bacterial effectors in modulating host signal transduction pathways. Our recent work has led to several interesting discoveries. 1) The OspF family of type III effectors, conserved in Shigella, Salmonella and the plant pathogen P. syringae, harbors a novel phosphothreonine lyase activity that specifically and irreversibly "dephosphorylates" host MAPKs, leading to kinase inactivation and inhibited cytokine production. 2) The Legionella type IV effector LegK1 mimics host IKK to phosphorylate IkBa, which results in ubiquitination and degradation of IkBa and consequent activation of host anti-apoptotic NF-kB signaling. 3) Type III effectors CHBP (Burkholderia) and Cif (EPEC) use a papain-like catalytic activity to deamidate ubiquitin and ubiquitin-like protein NEDD8. This leads to dysfunctioning of host ubiquitin-proteasome system, and therefore many important cellular processes such as cell cycle progression become abnormal. We believe that such kind of research and discovery is not only revealing in bacterial pathogenesis, but also provides an unprecedented unique angle for studying the mechanism of eukaryotic signal transduction. Meanwhile, we are also interested in how the host uses its innate immunity system to counteract bacterial infection, particularly the inflammasome pathway in macrophages. Macrophage senses many kinds of pathogen-derived molecular patterns and thereby activates the cytoplasmic inflammasome complex, and this leads to Il-1b production and inflammatory cell death of the macrophage. The NOD-like receptor in inflammasome is required for sensing bacteria-derived signals. However, little is known about how the inflammasome is assembled/activated, and the signaling cascade upstream of the inflammasome remains obscure. We are combining multiple approaches including biochemical reconstitution, cell biology and mouse genetics to identify new components in pathogen-induced inflammasome activation and to further reveal the underlying biochemical mechanism.
Yao Q, Cui J, Wang J, Li T, Wan X, Luo T, Gong YN, Xu Y, Huang N, Shao F. (2012) Ubiquitin/NEDD8 deamidation by bacterial effectors: structural mechanism and macrophage-specific apoptosis , Proc. Natl. Acad. Sci., 109(50):20395-400.
Dong N, Zhu Y, Lu Q, Hu L, Zheng Y, Shao F. (2012) Structurally Distinct Bacterial TBC-like GAPs Link Arf GTPase to Rab1 Inactivation to Counteract Host Defenses. Cell, 150, 1029-41.
Ge J, Gong YN, Xu Y, Shao F. (2012) Preventing bacterial DNA release and absent in melanoma 2 inflammasome activation by a Legionella effector functioning in membrane trafficking. Proc. Natl. Acad. Sci., 109, 6193-8.
Zhang L, Ding X, Cui J, Xu H, Chen J, Gong YN, Hu L, Zhou Y, Ge J, Lu Q, Liu L, Chen S, Shao F. (2012) Cysteine methylation disrupts ubiquitin-chain sensing in NF-kB activation. Nature, 481, 204-8.
Zhao Y, Yang J, Shi J, Gong YN, Lu Q, Xu H, Liu L, Shao F. (2011) The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus. Nature, 477, 596-600.
Cui J, Yao Q, Li S, Ding X, Lu Q, Mao H, Liu L, Zheng N, Chen S, Shao F. (2010) Glutamine deamidation and dysfunction of ubiquitin/NEDD8 induced by a bacterial effector family. Science, 329, 1215-8.
Gong YN, Wang X, Wang J, Yang Z, Li S, Yang J, Liu L, Lei X, Shao F. (2010) Chemical probing reveals insights into the signaling mechanism of inflammasome activation. Cell Research, 20, 1289-305.
Dong N, Liu L, Shao F. (2010) A bacterial effector targets host DH-PH domain RhoGEFs and antagonizes macrophage phagocytosis. EMBO J., 29, 1363-76.
Zhu Y, Hu L, Zhou Y, Yao Q, Liu L, Shao F. (2010) Structural mechanism of host Rab1 activation by the bifunctional Legionella type IV effector SidM/DrrA. Proc. Natl. Acad. Sci., 107, 4699-704.
Ge J, Xu H, Li T, Zhou Y, Zhang Z, Li S, Liu L, Shao F. (2009) A Legionella type IV effector activates the NF-κB pathway by phosphorylating the IκB family of inhibitors. Proc. Natl. Acad. Sci., 106, 13725-30.
Chen Y, Yang Z, Meng M, Zhao Y, Dong N, Yan H, Liu L, Ding M, Peng, HB, Shao F. (2009) Cullin mediates degradation of RhoA through evolutionarily conserved BTB adaptors to control actin cytoskeleton structure and cell movement. Mol. Cell, 35, 841-55.
Yao Q, Cui J, Zhu Y, Wang G, Hu L, Long C, Cao, R, Liu X, Huang N, Chen S, Liu L, Shao F. (2009) A bacterial type III effector family uses the papain-like hydrolytic activity to arrest the host cell cycle. Proc. Natl. Acad. Sci., 106, 3716-21.
Zhu Y., Li H., Hu L., Wang, J., Zhou Y., Pang Z., Liu L., Shao F. (2008) Structure of a Shigella effector reveals a new class of ubiquitin ligases. Nature Structural & Molecular Biology, 15, 1302-8.
Zhu Y, Li H, Long C, Hu L, Xu H, Liu L, Chen S, Wang DC, Shao F. (2007) Structural insights into the enzymatic mechanism of the pathogenic MAPK phosphothreonine lyase. Mol. Cell, 28, 899-913.
Zhang J, Shao F, Li Y, Cui H, Chen L, Li H, Zou Y, Long C , Lan L, Chai J, Chen S, Tang X, Zhou JM. (2007) A Pseudomonas syringae effector inactivates MAPKs to suppress PAMP-induced immunity. Cell Host & Microbe, 1, 175-85.
Li H, Xu H, Zhou Y, Zhang J, Long C, Li S, Chen S, Zhou JM, Shao F. (2007) The phosphothreonine lyase activity of a bacterial type III effector family. Science, 315, 1000-3.
Alto NM, Shao F, Lazar CS, Brost RL, Chua G, Mattoo, SM, McMahon SA, Ghosh P, Hughes TR, Boone C, Dixon JE. (2006) Identification of a bacterial type III effector family with G-protein mimicry functions. Cell, 124, 133-45.
Zhu M, Shao F, Innes RW, Dixon JE, Xu Z. (2004) The crystal structure of Pseudomonas avirulence protein AvrPphB: a papain-like fold with a distinct substrate-binding site. Proc. Natl. Acad. Sci., 101, 302-7.
Shao F, Golstein, C, Ade J, Stoutemyer M., Dixon JE, Innes RW. (2003) Cleavage of Arabidopsis PBS1 by a bacterial type III effector. Science, 301, 1230-3.
Shao F, Vacratsis PO, Bao Z, Bowers KE, Fierke CA, Dixon JE. (2003) Biochemical characterization of the Yersinia YopT protease: cleavage site and recognition elements in Rho GTPases. Proc. Natl. Acad. Sci., 100, 904-9.
Shao F, Merritt PM, Bao Z, Innes RW, Dixon JE. (2002) A Yersinia effector and a Pseudomonas avirulence protein define a family of cysteine proteases functioning in bacterial pathogenesis. Cell, 109, 575-88.
Shao F, Bader MW, Jakob U, Bardwell JC. (2000) DsbG, a protein disulfide isomerase with chaperone activity. J. Biol. Chem., 275, 13349-52.
Shao F, Hu Z, Xiong YM, Huang QZ, Wang CG, Zhu RH, Wang DC. (1999) A new antifungal peptide from the seeds of Phytolacca americana: characterization, amino acid sequence and cDNA cloning. Biochim. Biophys. Acta, 1430, 262-8.
Shao F, Xiong YM, Zhu RH, Ling M, Chi CW, Wang DC. (1999) Expression and purification of the BmK M1 neurotoxin from the scorpion Buthus martensii Karsch. Protein Expr. Purif., 17, 358-65.
Zhao Y, Shao F. (2012) NLRC5: a NOD-like receptor protein with many faces in immune regulation. Cell Research, 22, 1099-101.
Gong YN, Shao F. (2012) Sensing bacterial infections by NAIP receptors in NLRC4 inflammasome activation. Protein & Cell, 3, 98-105.
Ge J, Shao F. (2011) Manipulation of host vesicular trafficking and innate immune defense by Legionella Dot/Icm effectors. Cell. Microbiol., 13, 1870-80.
Cui J, Shao F. (2011) Biochemistry and cell signaling taught by bacterial effectors. Trends in Biochemical Sciences, 36, 532-40.
Shao F. (2008) Biochemical functions of Yersinia type III effectors. Current Opinion in Microbiology, 11, 21-9.
Juris SJ, Shao F, Dixon JE. (2002) Yersinia effectors target mammalian signaling pathways. Cell. Microbiol., 4: 201-11 (Co-first author).