邵峰 博士

北京生命科學(xué)研究所學(xué)術(shù)副所長(zhǎng)、資深研究員

Feng Shao, Ph.D. Investigator and Deputy Director for Academic Affairs, NIBS, Beijing, China

Phone：010-80726688-8560

Fax： 010-80728046

E-mail：shaofeng@nibs.ac.cn

教育經(jīng)歷

Education

工作經(jīng)歷

Professional Experience

研究概述

Research Description

我們實(shí)驗(yàn)室的研究興趣集中在病原細(xì)菌感染宿主和宿主先天性免疫防御的分子機(jī)制。對(duì)于細(xì)菌感染來(lái)說(shuō)，通過(guò)特殊的分泌系統(tǒng)向宿主細(xì)胞中注入毒素效應(yīng)蛋白是病原細(xì)菌普遍采用的重要致病機(jī)制。這些效應(yīng)蛋白往往以非常有效的方式作用于宿主信號(hào)轉(zhuǎn)導(dǎo)中的關(guān)鍵分子，使其發(fā)生功能紊亂。效應(yīng)蛋白的作用有利于細(xì)菌在宿主中的生存和進(jìn)一步感染。我們的研究以多種臨床上常見(jiàn)的病原菌（Shigella, Salmonella, Enteropathogenic E. coli, Legionella 以及Burkholderia）為模式，著眼于發(fā)現(xiàn)并揭示效應(yīng)蛋白在抑制真核細(xì)胞重要信號(hào)轉(zhuǎn)導(dǎo)通路中的一些新的、較為普遍的生物化學(xué)機(jī)制。實(shí)驗(yàn)室最近的研究工作在這方面取得了一系列的突破和發(fā)現(xiàn)。1) 來(lái)源于Shigella，Salmonella和植物假單胞桿菌的OspF家族三型分泌系統(tǒng)效應(yīng)蛋白通過(guò)一種嶄新的磷酸化蘇氨酸裂合酶的活性，特異性地、不可逆地“去磷酸化”宿主MAPK激酶并使其失活,從而抑制宿主細(xì)胞因子的表達(dá)。2) Legionella的四型分泌系統(tǒng)效應(yīng)蛋白LegK1能模擬宿主中的IKK激酶而磷酸化IκBa蛋白，并誘導(dǎo)其被泛素化和降解，進(jìn)而激活NF-κB通路并對(duì)巨噬細(xì)胞凋亡產(chǎn)生抑制作用。3)三型分泌系統(tǒng)效應(yīng)蛋白CHBP（Burkholderia）和Cif（Enteropathogenic E. coli）特異性地修飾（脫氨）泛素和泛素樣蛋白NEDD8中Gln-40。這種修飾能有效地阻斷宿主泛素-蛋白酶體通路并導(dǎo)致諸如細(xì)胞周期等重要細(xì)胞生理過(guò)程發(fā)生功能紊亂。我們認(rèn)為，這些研究不僅對(duì)理解感染和致病的分子機(jī)理有極大的促進(jìn)作用，更為重要的是，由于病原細(xì)菌和宿主(人類)長(zhǎng)期共同進(jìn)化，其分泌的毒素效應(yīng)蛋白也為我們研究真核細(xì)胞本身的信號(hào)轉(zhuǎn)導(dǎo)機(jī)制提供了獨(dú)特的、前所未有的視角和研究工具。同時(shí)，我們也對(duì)宿主巨噬細(xì)胞如何通過(guò)其先天性免疫系統(tǒng)來(lái)拮抗病原微生物感染的機(jī)制感興趣。在受到感染后，巨噬細(xì)胞能感受到多種來(lái)自病原菌或其它病原微生物的一些模式分子，從而激活一類被稱為炎癥小體的蛋白復(fù)合物，同時(shí)發(fā)生炎癥性細(xì)胞壞死和分泌白介素1b。炎癥小體利用一類叫作NOD-like的受體分子感受來(lái)自病原菌的信號(hào)，但除此之外人們對(duì)炎癥小體的組裝和其上游的信號(hào)轉(zhuǎn)導(dǎo)機(jī)制了解甚少。我們將結(jié)合生物化學(xué)、細(xì)胞生物學(xué)以及小鼠遺傳學(xué)等多種手段來(lái)研究和闡明炎癥小體被激活的生化機(jī)制。

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 asShigella, 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 Legionellatype 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.

Representative Publications:

1. Zhong X, Zeng H, Zhou Z, Su Y, Cheng H, Hou Y, She Y, Feng N, Wang J, Shao F, Ding J.(2023) Structural mechanisms for regulation of GSDMB pore-forming activity. Nature, 616, 598-605.

2. Li Z, Liu W,Fu J, Cheng S, Xu Y, Wang Z, Liu X, Shi X, Liu Y, Qi X, Liu X, Ding J, Shao F.(2021) Shigella evades pyroptosis by arginine ADP-riboxanation of caspase-11. Nature, 599, 290-295.

3. Zhou Z, He H, Wang K, Shi X, Wang Y, Su Y, Wang Y, Li D, Liu W, Zhang Y, Shen L, Han W, Shen L, Ding J, Shao F.(2020) Granzyme A from cytotoxic lymphocytes cleaves GSDMB to trigger pyroptosis in target cells. Science, 368, 6494.

4. Wang Q, Wang Y, Ding J, Wang C, Zhou X, Gao W, Huang H, Shao F, Liu Z.(2020) A bioorthogonal system reveals antitumour immune function of pyroptosis. Nature, 579,421-426.

5. Wang K, Sun Q, Zhong X, Zeng M, Zeng H, Shi X, Li Z, Wang Y, Zhao Q, Shao F, Ding J.(2020) Structural mechanism for GSDMD targeting by autoprocessed caspases in pyroptosis. Cell, 2020,180, 941-955.

6. Xu Y, Zhou P, Cheng S, Lu Q, Nowak K, Hopp A, Li L, Shi X, Zhou Z, Gao W, Li D, He H, Liu X, Ding J, Hottiger M, Shao F. (2019) A Bacterial effector reveals the V-ATPase-ATG16L1 axis that initiates xenophagy, Cell, 178, 1-15.

7. Zhou P, She Y, Dong N, Li P, He H, Borio A, Wu Q, Lu S, Ding X, Cao Y, Xu Y, Gao W, Dong M, Ding J, Wang DC, Zamyatina A, Shao F. (2018) Alpha-kinase 1 is a cytosolic innate immune receptor for bacterial ADP-heptose, Nature, 561, 122-126 (Published online Aug 15).

8. Li P, Jiang W, Yu Q, Liu W, Zhou P, Li J, Xu J, Xu B, Wang F & Shao F. (2017) Ubiquitination and degradation of GBPs by a Shigella effector to suppress host defense, Nature, 551, 378-383 (Published online Oct 11).

9. Wang Y, Gao W, Shi X, Ding J, Liu W, He H, Wang K & Shao F. (2017) Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a Gasdermin, Nature, 547 (7661), 99-103 (Published online May 01).

10. Ding J, Wang K, Liu W, She Y, Sun Q, Shi J, Sun H, Wang DC & Shao F. (2016) Pore-forming activity and structural autoinhibition of the Gasdermin family, Nature (Article), 535 (7610), 111-116 (Published online 08 June 2016).

11. Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, Zhuang Y, Cai T, Wang F & Shao F. (2015) Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death, Nature (Article), 526, 660–665.

12. Lu Q, Yao Q, Xu Y, Li L, Li S, Liu Y, Gao W, Niu M, Sharon M, Ben-Nissan G, Zamyatina A, Liu X, Chen S & Shao F. (2014) An iron-containing dodecameric heptosyltransferase family modifies bacterial autotransporters in pathogenesis, Cell Host & Microbe, 16, 351–363.

13. Shi J, Zhao Y, Wang Y, Gao W, Ding J, Li P, Hu L & Shao F. (2014) Inflammatory caspases are innate immune receptors for intracellular LPS, Nature (Article), 514, 187-192 (Published online 06 August 2014).

14. Xu H, Yang J, Gao W, Li L, Li P, Zhang L, Gong YN, Peng X, Xi JJ, Chen S, Wang F, Shao F. (2014) Innate immune sensing of bacterial modifications of Rho GTPases by the Pyrin inflammasome. Nature, 513, 237–241 (Published online 11 June 2014).

15. Li S, Zhang L, Yao Q, Li L, Dong N, Rong J, Gao W, Ding X, Sun L, Chen X, Chen S & Shao F. (2013) Pathogen blocks host death receptor signaling by arginine GlcNAcylation of death domains. Nature, 501, 242-246.

16. Yang J, Zhao Y, Shi J & Shao F. (2013) Human NAIP and mouse NAIP1 recognize bacterial type III secretion needle protein for inflammasome activation. Proc. Natl. Acad. Sci., 110, 14408-13.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

Other Publications:

Research articles:

1. Hou Y, Zeng H, Li Z, Feng N, Meng F, Xu Y, Li L, Shao F, Ding J.(2023) Structural mechanisms of calmodulin activation of Shigella effector OspC3 to ADP-riboxanate caspase-4/11 and block pyroptosis. Nature Structural & Molecular Biology, 30, 261-272.

2. Li X, Liao C, Xu Y, Lu Q, Chen S, Su L, Zou Y, Shao F, Liu W, Zhang W, Hu H.(2022) Configuration-specific antibody for bacterial heptosylation: an antiadhesion therapeutic strategy. Journal of the American Chemical Society, 145, 322-333.

3. Cao S, Jiao Y, Jiang W, Wu Y, Qin S, Ren Y, You Y, Tan Y, Guo X, Chen H, Zhang Y, Wu G, Wang T, Zhou Y, Song Y, Cui Y, Shao F, Yang R, Du Z.(2022) Subversion of GBP-mediated host defense by E3 ligases acquired during Yersinia pestis evolution. Nature Communications, 13,4526.

4. Liu Y, Zeng H, Hou Y, Li Z, Li L, Song X, Ding J, Shao F.(2022) Calmodulin binding activates Chromobacterium CopC effector to ADP-riboxanate host apoptotic caspases. Mbio. 13, e00690-22.

5. Fattinger SA, Maurer L, Geiser P, Enz U, Ganguillet S, Gul E, Kroon S, Demarco B, Furter M, Barthel M, Pelczar P, Shao F, Broz P, Sellin ME, Harde WD.(2022) Gasdermin D is the only Gasdermin that provides non-redundant protection against acute Salmonella gut infection. bioRxiv, 2022.11. 24.517575.

6. Xu Y, Cheng S, Zeng H, Zhou P, Ma Y, Li L, Liu X, Shao F, Ding J.(2022) ARF GTPases activate Salmonella effector SopF to ADP-ribosylate host V-ATPase and inhibit endomembrane damage-induced autophagy. Nature Structural & Molecular Biology, 29, 67-77.

7. Wan X, Li J, Wang Y, Yu X, He X, Shi J, Deng G, Zeng X, Tian G, Li Y, Jiang Y, Guan Y, Li C, Shao F, Chen L.(2022) H7N9 virus infection triggers lethal cytokine storm by activating gasdermin E-mediated pyroptosis of lung alveolar epithelial cells. National Science Review, 9, nwab137.

8. Ventayol PS, Geiser P, Martino M, Florbrant A, Fattinger SA, Walder N, Sima E, Shao F, Gekara NO, Sundbom M, Hardt WD, Webb DL, Hellstr?m PM, Eriksson J, Sellin ME(2021) Bacterial detection by NAIP/NLRC4 elicits prompt contractions of intestinal epithelial cell layers. Proceedings of the National Academy of Sciences, 118, e2013963118.

9. Zhang C, Song J, Huang H, Fan X, Huang L, Deng J, Tu B, Wang K, Li J, Zhou M, Yang C, Zhao Q, Yang T, Wang L, Zhang J, Xu R, Jiao Y, Shi M, Shao F, Sékaly R, Wang F (2020) NLRP3 inflammasome induces CD4+ T cell loss in chronically HIV-1–infected patients, The Journal of Clinical Investigation, 131 (6).

10. Karmakar M, Minns M, Greenberg E, Diaz-Aponte J, Pestonjamasp K, Johnson J, Rathkey J, Abbott D, Wang K, Shao F, Catz S, Dubyak G, Pearlman E (2020) N-GSDMD trafficking to neutrophil organelles facilitates IL-1β release independently of plasma membrane pores and pyroptosis, Nature communications, 11, 1-14.

11. Ji C, Du S, Li P, Zhu Q, Yang X, Long C, Yu J, Shao F, Xiao J. (2019) Structural mechanism for guanylate-binding proteins (GBPs) targeting by the Shigella E3 ligase IpaH9. 8, PLoS pathogens, 15, e1007876.

12. Wu C, Lu W, Zhang Y, Zhang G, Shi X, Hisada Y, Grover S, Zhang X, Li L, Xiang B, Shi J, Li X, Daugherty A, Smyth S, Kirchhofer D, Shiroishi T, Shao F, Mackman N, Wei Y, Li Z. (2019) Inflammasome activation triggers blood clotting and host death through pyroptosis, Immunity, 50, 1401-1411.

13. Ding J, Pan X, Du L, Yao Q, Xue J, Yao H, Wang D, Li S, Shao F. (2019) Structural and functional insights into host death domains inactivation by the bacterial arginine GlcNAcyltransferase effector, Molecular Cell, 74, 1-14.

14. Rathinam V, Zhao Y, Shao F. (2019) Innate immunity to intracellular LPS, Nature Immunology, 20, 527-533.

15. Xu H, Shi J, Gao H, Liu Y, Yang Z, Shao F, Dong N. (2019) The N-end rule ubiquitin ligase UBR2 mediates NLRP1B inflammasome activation by anthrax lethal toxin, EMBO, 38(13):e101996.

16. Liu W, Zhou Y, Peng T, Zhou P, Ding X, Li Z, Chen S, Hang HC, and Shao F. (2018) N^e-fatty acylation of multiple membrane-associated proteins by Shigella IcsB effector to modulate host function, Nature Microbiology, 3, 996-1009.

17. Adanitsch F, Shi J, Shao F, Beyaert R, Heine H, and Zamyatina A. (2018) Synthetic glycan-based TLR4 agonists targeting Caspase-4/11 for the development of adjuvants and immunotherapeutics, Chem. Sci., 9, 3957-3963.

18. Yang J, Zhao Y, Li P, Yang Y, Zhang E, Zhong M, Li Y, Zhou D, Cao Y, Lu M, Shao F#, Yan H#. (2018) Sequence determinants of specific pattern-recognition of bacterial ligands by the NAIP-NLRC4 inflammasome, Cell Discovery,4: 22. doi: 10.1038/s41421-018-0018-1 (# corresponding authors).

19. Lin R, Feng Q, Li P, Zhou P, Wang R, Liu Z, Wang Z, Qi X, Tang N, Shao F, Luo M. (2018). A hybridization-chain-reaction-based method for amplifying immunosignals, Nature Methods, 15, 275-278.

20. Xu B, Jiang M, Chu Y, Wang W, Chen D, Li X, Zhang Z, Zhang D, Fan D, Nie Y, Shao F, Wu K, Liang J. (2018) Gasdermin D plays a key role as a pyroptosis executor of non-alcoholic steatohepatitis in humans and mice, J Hepatol., 68, 773-782.

21. Zhou Y, Huang C, Yin L, Wan M, Wang X, Li L, Liu Y, Wang Z, Fu P, Zhang N, Chen S, Liu X, Shao F, Zhu Y. (2017). N^ε-Fatty acylation of Rho GTPases by a MARTX toxin effector, Science. 358, 528-531.

22. Sheng X, You Q, Zhu H, Chang Z, Li Q, Wang H, Wang C, Wang H, Hui L, Du C, Xie X, Zeng R, Lin A, Shi D, Ruan K, Yan J, Gao GF, Shao F, Hu R. (2017) Bacterial effector NleL promotes enterohemorrhagic E. coli-induced attaching and effacing lesions by ubiquitylating and inactivating JNK, PLoS Pathogen,13(7): e1006534.

23. Litvak Y, Sharon S, Hyams M, Zhang L, Kobi S, Katsowich N, Dishon S, Nussbaum G, Dong N, Shao F, and Rosenshine I. (2017) Epithelial cells detect functional type III secretion system of enteropathogenic Escherichia coli through a novel NF-κB signaling pathway. PLoS Pathogen, 13(7): e1006472.

24. Dong N, Niu M, Hu L, Yao Q, Zhou R, and Shao F. (2016) Modulation of membrane phosphoinositide dynamics by the phosphatidylinositide 4-kinase activity of the Legionella LepB effector, Nature Microbiology, 2:16236.

25. Thurston TL, Matthews SA, Jennings E, Alix E, Shao F, Shenoy AR, Birrell MA, Holden DW. (2016) Growth inhibition of cytosolic Salmonella by caspase-1 and caspase-11 precedes host cell death, Nature Communications, 7:13292.

26. Gao W, Yang J, Liu W, Wang Y, Shao F. (2016) Site-specific phosphorylation and microtubule dynamics control Pyrin inflammasome activation, Proc. Natl. Acad. Sci., 113, E4857-66.

27. Zhang Q, Zhou A, Li S, Ni J, Tao J, Lu J, Wan B, Li S, Zhang J, Zhao S, Zhao GP, Shao F, Yao YF (2016) Reversible lysine acetylation is involved in DNA replication initiation by regulating activities of initiator DnaA in Escherichia coli, Sci Rep., 6: 30837.

28. Aubert DF, Xu H, Yang J, Gao W, Li L, Chen S, Valvano MA, Shao F. (2016) A Burkholderia type VI effector deamidates Rho GTPases to activate the Pyrin inflammasome, Cell Host & Microbe, 19, 664-674.

29. Zhao Y, Shi J, Shi X, Wang Y, Wang F & Shao F. (2016) Genetic functions of the NAIP family of inflammasome receptors for bacterial ligands in mice, Journal of Experimental Medicine, 213(5), 647-56.

30. Zanoni I, Tan Y, Di Gioia M, Broggi A, Ruan J, Shi J, Donado CA, Shao F, Wu H, Springstead JR, Kagan JC. (2016) An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells, Science, 352(6290), 1232-6.

31. 24. Hu Z, Zhou Q, Zhang C, Fan S, Cheng W, Zhao Y, Shao F, Wang HW, Sui SF, Chai J. (2015) Structural and biochemical basis for induced self-propagation of NLRC4, Science, 350, 399-404.

32. Lu Q, Xu Y, Yao Q, Niu M and Shao F. (2015) A polar-localized iron-binding protein determines the polar targeting of Burkholderia BimA autotransporter and actin tail formation, Cellular Microbiology, 17, 408–424.

33. Yao Q, Zhang L, Wan X, Chen J, Hu L, Ding X, Li L, Karar J, Peng H, Chen S, Huang N, Rauscher FJ, Shao F. (2014) Structure and Specificity of the Bacterial Cysteine Methyltransferase Effector NleE Suggests a Novel Substrate in Human DNA Repair Pathway. PLoS Pathogens, 10: e1004522.

34. Yao Q, Lu Q, Wan X, Song F, Xu Y, Zamyatina A, Huang N, Zhu P & Shao F. (2014) A structural mechanism for bacterial autotransporter glycosylation by a dodecameric heptosyltransferase family, eLife, 3: e03714.

35. Pan M, Li S, Li X, Shao F, Liu L and Hu HG (2014) Synthesis and Specific Antibody Generation of Glycopeptides with Arginine N-GlcNAcylation. Angew Chem Int Ed Engl., 53, 14517-14521 (co-corresponding author).

36. Ding J, Luo AF, Hu L, Wang DC, Shao F. (2014) Structural basis of the ultrasensitive calcium indicator GCaMP6. SCIENCE CHINA Life Sciences, 57, 269–274.

37. Li T, Lu Q, Wang G, Xu H, Huang H, Cai T, Kan B, Ge J & Shao F. (2013) SET-domain bacterial effectors target heterochromatin protein 1 to activate host rDNA transcription. EMBO Reports, 14, 733-40.

38. Yu Q, Hu L, Yao Q, Zhu Y, Dong N, Wang DC, Shao F. (2013) Structural analyses of a Legionella RabGAP effector reveal a new GAP fold that catalytically mimics eukaryotic RasGAP. Cell Research, 23, 775-87.

39. Zhou Y, Dong N, Hu L, Shao F. (2013) The Shigella Type Three Secretion System Effector OspG Directly and Specifically Binds to Host Ubiquitin for Activation. PLoS One, 8: e57558.

40. Yao Q, Cui J, Wang J, Li T, Wan X, Luo T, Gong YN, Xu Y, Huang N, Shao F. (2012) Structural mechanism of ubiquitin and NEDD8 deamidation catalyzed by bacterial effectors that induce macrophage-specific apoptosis. Proc. Natl. Acad. Sci., 109, 20395-400.

41. Ku B, Lee KH, Park WS, Yang CS, Ge J, Lee SG, Cha SS, Shao F, Heo WD, Jung JU, Oh BH. (2012) VipD of Legionella pneumophila targets activated Rab5 and Rab22 to interfere with endosomal trafficking in macrophages. PLoS Pathogen, 8: e1003082.

42. 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.

43. He S, Liang Y, Shao F, Wang X. (2011) Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3–mediated pathway. Proc. Natl. Acad. Sci., 108, 20054-9.

44. Li C, Tu S, Wen S, Li S, Chang J, Shao F, and Lei X. (2011) Total Synthesis of the G2/M DNA Damage Checkpoint Inhibitor Psilostachyin C. The Journal of Organic Chemistry, 76, 3566-70.

45. 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.

46. Dong N, Liu L, Shao F. (2010) A bacterial effector targets host DH-PH domain RhoGEFs and antagonizes macrophage phagocytosis. The EMBO J., 29, 1363-76.

47. 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.

48. 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.

49. 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.

50. Dowen RH, Engel JL, Shao F, Ecker JR, Dixon JE. (2009) A family of bacterial cysteine protease type III effectors utilizes acylation-dependent and -independent strategies to localize to plasma membranes. J. Biol. Chem., 284, 15867-79.

51. 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.

52. 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.

53. 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.

54. 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.

55. 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.

56. Armstrong MB, Bian X, Liu Y, Subramanian C, Ratanaproeska AB, Shao F, Yu V, Kwok R, Opipari AW, Jr., Castle VP. (2006) Signaling from p53 to NF-kappaB determines chemotherapy responsiveness of neuroblastoma. Neoplasia, 8, 964-74.

57. 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.

58. 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.

59. Shao F, Vacratsis PO, Bao Z, Bowers KE, Fierke CA, Dixon JE. (2003) Biochemical characterization of the YersiniaYopT protease: cleavage site and recognition elements in Rho GTPases. Proc. Natl. Acad. Sci., 100, 904-9.

60. 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.

61. Bian X, McAllister-Lucas LM, Shao F, Schumacher KR, Feng Z, Porter AG, Castle VP, Opipari AW, Jr. (2001) NF-kappa B activation mediates doxorubicin-induced cell death in N-type neuroblastoma cells. J. Biol. Chem., 276, 48921-9.

62. Shao F, Bader MW, Jakob U, Bardwell JC. (2000) DsbG, a protein disulfide isomerase with chaperone activity. J. Biol. Chem., 275, 13349-52.

63. Wang CG, He XL, Shao F, Liu W, Ling MH, Wang DC, Chi CW. (2001) Molecular characterization of an anti-epilepsy peptide from the scorpion Buthus martensi Karsch. Eur. J. Biochem., 268, 2480-5.

64. 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.

65. 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.

a) Invited review articles:

66. Schubert KA, Xu Y, Shao F, Auerbuch V. (2020) The Yersinia Type III Secretion System as a Tool for Studying Cytosolic Innate Immune Surveillance, Annual Review of Microbiology, 74, 221-245.

67. Broz P, Pelegrín P, Shao F (2020) The gasdermins, a protein family executing cell death and inflammation, Nature Reviews Immunology, 20,143-157

68. Ding J, Shao F. (2018) Growing a gasdermin pore in membranes of pyroptotic cells. The EMBO J., 37(15). pii: e100067.

69. Dong N, Shao F. (2019) Molecular mechanism and immunological function of pyroptosis, SCIENTIA SINICA, 49, 1606-1634

70. Basler M, Shao F. (2018) Bacterial infection and symbiosis. Mol Biol Cell. 29 (6), 683-684.

71. Galluzzi L, ?, Shao F, ?, Kroemer, G. (2018) Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death & Differentiation, 25 (3), 486-541.

72. Schroder K, Kanneganti TD, Shao F, Broz P. (2018) Mechanisms of Inflammasome Activation. J Mol Biol., 430 (2), 131-132.

73. Ding J, Shao F. (2017) SnapShot: The Noncanonical Inflammasome, Cell, 168:544-544.e1.

74. Shi J, Gao W, Shao F. (2017) Pyroptosis: Gasdermin-mediated programmed necrotic cell death, Trends in Biochemical Sciences, 42 (4), 245–254.

75. Zhao Y, Shao F. (2016) Diverse mechanisms for inflammasome sensing of cytosolic bacteria and bacterial virulence, Current Opinion in Microbiology, 29, 37-42.

76. Lu Q, Li Shan, Shao F. (2015) Sweet talk: protein glycosylation in bacterial interaction with the host. Trends in Microbiology, 23, 630-41 (Cover article).

77. Zhao Y, Shao F. (2015) The NAIP-NLRC4 inflammasome in innate immune detection of bacterial flagellin and type III secretion apparatus. Immunological Reviews, 265, 85-102.

78. Yang J, Zhao Y, Shao F. (2015) Non-canonical activation of inflammatory caspases by cytosolic LPS in innate immunity. Current Opinion in Immunology, 32, 78–83.

79. Yang J, Xu H, Shao F. (2014) The immunological function of familial Mediterranean fever disease protein Pyrin. SCIENCE CHINA Life Sciences, 57, 1156-1161.

80. Zhao Y, Shao F. (2012) NLRC5: a NOD-like receptor protein with many faces in immune regulation. Cell Research, 22, 1099-101.

81. Gong YN, Shao F. (2012) Sensing bacterial infections by NAIP receptors in NLRC4 inflammasome activation. Protein & Cell, 3, 98-105.

82. Ge J, Shao F. (2011) Manipulation of host vesicular trafficking and innate immune defense by Legionella Dot/Icm effectors. Cell. Microbiol., 13, 1870-80.

83. Cui J, Shao F. (2011) Biochemistry and cell signaling taught by bacterial effectors. Trends in Biochemical Sciences, 36, 532-40.

84. Shao F. (2008) Biochemical functions of Yersinia type III effectors. Current Opinion in Microbiology, 11, 21-9.

85. Juris SJ, Shao F, Dixon JE. (2002) Yersinia effectors target mammalian signaling pathways. Cell. Microbiol., 4, 201-11 (Co-first author).