专家人才库数据----中国科学院上海巴斯德研究所

Principal investigator2016

Name:	Xing LIU	Gender:
Education:	2007-2012, Ph.D., Shanghai Institute of Biochemistry and Cell Biology, CAS 2003-2007, B.S., East China Normal University (ECNU)
Academic degree:	Ph.D.	Academic title:	Principal Investigator
Departments:	Anti-infection Immunity and Immune Diseases	Discipline:	Immune Response and Immunotherapy
Phone:	86-21-54923080	E-mail:	xingliu@ips.ac.cn
Mailing Address:	Life Science Research Building 320 Yueyang Road, Xuhui District, 200031

Curriculum vitae:
2018-present, Principle investigator, Institut Pasteur of Shanghai, CAS 2016-2018, Instructor, Harvard Medical School/ Boston Children’s Hospital 2014-2016, Postdoctoral fellow, Harvard Medical School/ Boston Children’s Hospital 2012-2014, Postdoctoral fellow, Shanghai Institute of Biochemistry and Cell Biology, CAS

Research direction:
Our lab has been working on investigating the molecular and cellular mechanisms during host anti-pathogen immune responses, aiming to identify novel regulators and mediators, thus providing therapeutic targets and strategies for treating associated inflammatory and autoimmune diseases. One of our major focuses is pyroptosis, a programmed inflammatory cell death triggered by cytosolic sensing of invasive infection and danger signals. Gasdermins (GSDMs), a family of homologous pore-forming proteins, were recently identified as key executioners of pyroptosis. Our previous work (and others) identified the N-terminal fragments of GSDMD (GSDMD-NT) liberated via inflammatory caspase cleavage assemble in cell membranes and form pores, disrupting cell membrane integrity and trigger pyroptosis. In another study, we screened 3,752 small molecules and identified disulfiram, a drug approved by FDA for treating alcohol addiction, as an inhibitor of GSDMD pore formation. Disulfiram blocks pyroptosis and cytokine release in cells and lipopolysaccharide-induced septic death in mice, providing new therapeutic indications for repurposing this safe drug to counteract inflammation and human diseases. Currently we are working on elucidating in depth the regulation and function of GSDMs at the root of host-pathogen interactions as well as their function in associated human diseases; Meanwhile, we are employing unbiased genome-wide CRISPR/Cas9 screen, high-throughput small molecules screen and structure-based drug design and optimization, to identify novel regulators or mediators involved in host defense against microbial pathogen infection.

Research direction:

Our lab has been working on investigating the molecular and cellular mechanisms during host anti-pathogen immune responses, aiming to identify novel regulators and mediators, thus providing therapeutic targets and strategies for treating associated inflammatory and autoimmune diseases. One of our major focuses is pyroptosis, a programmed inflammatory cell death triggered by cytosolic sensing of invasive infection and danger signals. Gasdermins (GSDMs), a family of homologous pore-forming proteins, were recently identified as key executioners of pyroptosis. Our previous work (and others) identified the N-terminal fragments of GSDMD (GSDMD-NT) liberated via inflammatory caspase cleavage assemble in cell membranes and form pores, disrupting cell membrane integrity and trigger pyroptosis. In another study, we screened 3,752 small molecules and identified disulfiram, a drug approved by FDA for treating alcohol addiction, as an inhibitor of GSDMD pore formation. Disulfiram blocks pyroptosis and cytokine release in cells and lipopolysaccharide-induced septic death in mice, providing new therapeutic indications for repurposing this safe drug to counteract inflammation and human diseases. Currently we are working on elucidating in depth the regulation and function of GSDMs at the root of host-pathogen interactions as well as their function in associated human diseases; Meanwhile, we are employing unbiased genome-wide CRISPR/Cas9 screen, high-throughput small molecules screen and structure-based drug design and optimization, to identify novel regulators or mediators involved in host defense against microbial pathogen infection.

Research progress:
*Selected Publications (First author, #Corresponding author) 01. Deng W, Bai Y, Deng F, Pan Y, Mei S, Zheng Z, Min R, Wu Z, Li W, Miao R, Zhang Z, Kupper T, Lieberman J and Liu X^#. Streptococcal pyrogenic exotoxin B cleaves GSDMA and triggers pyroptosis. Nature. 2022; doi: 10.1038/s41586-021-04384-4. 02. Zheng Z, Deng W, Bai Y, Miao R, Mei S, Zhang Z, Pan Y, Wang Y, Min R, Deng F, Wu Z, Li W, Chen P, Ma T, Lou X, Lieberman J^#and Liu X*^#. The lysosomal Rag-Ragulator complex licenses RIPK1- and Caspase-8-mediated pyroptosis by Yersinia. Science.* 2021; 372, eabg0269. 03. Liu X^#, Xia S, Zhang Z, Wu H^#, Lieberman J^#. Channeling inflammation: gasdermins in physiology and disease. *Nat Rev Drug Discov.* 2021; 20:384-405. 04. Hu J, Liu X^#, Xia S, Zhang Z, Zhang Y, Zhao J, Ruan J, Luo X, Lou X, Bai Y, Wang J, Hollingsworth L, Magupalli V, Zhao L, Luo H, Kim J, Lieberman J^# and Wu H^#. Disulfiram inhibits pyroptosis by blocking gasdermin D pore formation. *Nat Immunol.* 2020; (7):736-745. 05. Liu X^#, Lieberman J^#. Knocking 'em Dead: Pore-Forming Proteins in Immune Defense. *Annu Rev Immunol.* 2020; 38:455-485. 06. Zhang Z, Zhang Y, Xia S, Kong Q, Li S, Liu X, Junqueira C, Meza-Sosa K, Mok T, Ansara J, Sengupta S, Yao Y, Wu H, Lieberman J. Gasdermin E suppresses tumor growth by activating anti-tumor immunity. *Nature. 2020; 579(7799):415-420. 07. Cui S, Yu Q, Chu L, Cui Y, Ding M, Wang Q, Wang H, Chen Y, Liu X^#, Wang C^#. Nuclear cGAS Functions Non-canonically to Enhance Antiviral Immunity via Recruiting Methyltransferase Prmt5. Cell Rep.* 2020; 33(10):108490. 08. Liu X, Fu R, Pan Y, Meza-Sosa K, Zhang Z and Lieberman J. PNPT1 Release from Mitochondria during Apoptosis Triggers Decay of Poly(A) RNAs. Cell. 2018; 174(1):187-201.e12. 09. Ruan J, Xia S, Liu X, Lieberman J, and Wu H. Cryo-EM structure of the Gasdermin A3 membrane pore. Nature. 2018; 557(7703):62-67. 10. Li S, Hong Z, Wang Z, Li F, Mei J, Huang L, Lou X, Zhao S, Song L, Chen W, Wang Q, Liu H, Cai Y, Yu H, Xu H, Zeng G, Wang Q, Zhu J, Liu X^#, Tan N^#, and Wang C^#. The Cyclopeptide Astin C Specifically Inhibits the Innate Immune CDN Sensor STING. Cell Rep.* 2018; 25(12):3405-3421.e7. 11. Liu X and Lieberman J. How ICE lights the pyroptosis fire. *Cell Death Differ.* 2017; 24(2):197-199. 12. Pan Y, Tian T, Park C, Lofftus S, Mei S, Liu X, Luo C, O’Malley J, Gehad A, Teague J, Divito S, Fuhlbrigge R, Puigserver P, Krueger J, Hotamisligil G, Clark R, Kupper T. Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism. *Nature. 2017; 543(7644):252-256. 13. Liu X, Zhang Z, Ruan J, Pan Y, Magupalli V, Wu H, and Lieberman J. Inflammasome-activated Gasdermin D causes pyroptosis by forming membrane pores. Nature. 2016; 535(7610):153-8. 14. Wittrup A, Ai A, Liu X, Hamar P, Trifonova R, Charisse K, Manoharan M, Kirchhausen T, and Lieberman J. Visualizing lipid-formulated siRNA release from endosomes and target gene knockdown. Nat Biotechnol. 2015; 33(8):870-6. 15. Wang Q, Liu X^#, Cui Y, Tang Y, Chen W, Li S, Yu H, Pan Y, and Wang C^#. The E3 ubiquitin ligase AMFR and INSIG1 bridge the activation of TBK1 kinase by modifying the adaptor STING. Immunity*. 2014; 41(6):919-33. Cover Article.

Research progress:

Selected Publications (*First author, #Corresponding author)

01. Deng W, Bai Y, Deng F, Pan Y, Mei S, Zheng Z, Min R, Wu Z, Li W, Miao R, Zhang Z, Kupper T, Lieberman J and Liu X^#. Streptococcal pyrogenic exotoxin B cleaves GSDMA and triggers pyroptosis. Nature. 2022; doi: 10.1038/s41586-021-04384-4.

02. Zheng Z, Deng W, Bai Y, Miao R, Mei S, Zhang Z, Pan Y, Wang Y, Min R, Deng F, Wu Z, Li W, Chen P, Ma T, Lou X, Lieberman J^#and Liu X^#. The lysosomal Rag-Ragulator complex licenses RIPK1- and Caspase-8-mediated pyroptosis by Yersinia. Science. 2021; 372, eabg0269.

03. Liu X^#, Xia S, Zhang Z, Wu H^#, Lieberman J^#. Channeling inflammation: gasdermins in physiology and disease. Nat Rev Drug Discov. 2021; 20:384-405.

04. Hu J*, Liu X*^#, Xia S, Zhang Z, Zhang Y, Zhao J, Ruan J, Luo X, Lou X, Bai Y, Wang J, Hollingsworth L, Magupalli V, Zhao L, Luo H, Kim J, Lieberman J^# and Wu H^#. Disulfiram inhibits pyroptosis by blocking gasdermin D pore formation. Nat Immunol. 2020; (7):736-745.

05. Liu X^#, Lieberman J^#. Knocking 'em Dead: Pore-Forming Proteins in Immune Defense. Annu Rev Immunol. 2020; 38:455-485.

06. Zhang Z, Zhang Y, Xia S, Kong Q, Li S, Liu X, Junqueira C, Meza-Sosa K, Mok T, Ansara J, Sengupta S, Yao Y, Wu H, Lieberman J. Gasdermin E suppresses tumor growth by activating anti-tumor immunity. Nature. 2020; 579(7799):415-420.

07. Cui S, Yu Q, Chu L, Cui Y, Ding M, Wang Q, Wang H, Chen Y, Liu X^#, Wang C^#. Nuclear cGAS Functions Non-canonically to Enhance Antiviral Immunity via Recruiting Methyltransferase Prmt5. Cell Rep. 2020; 33(10):108490.

08. Liu X, Fu R, Pan Y, Meza-Sosa K, Zhang Z and Lieberman J*. PNPT1 Release from Mitochondria during Apoptosis Triggers Decay of Poly(A) RNAs. Cell. 2018; 174(1):187-201.e12.

09. Ruan J, Xia S, Liu X, Lieberman J, and Wu H. Cryo-EM structure of the Gasdermin A3 membrane pore. Nature. 2018; 557(7703):62-67.

10. Li S, Hong Z, Wang Z, Li F, Mei J, Huang L, Lou X, Zhao S, Song L, Chen W, Wang Q, Liu H, Cai Y, Yu H, Xu H, Zeng G, Wang Q, Zhu J, Liu X^#, Tan N^#, and Wang C^#. The Cyclopeptide Astin C Specifically Inhibits the Innate Immune CDN Sensor STING. Cell Rep. 2018; 25(12):3405-3421.e7.

11. Liu X and Lieberman J. How ICE lights the pyroptosis fire. Cell Death Differ. 2017; 24(2):197-199.

12. Pan Y, Tian T, Park C, Lofftus S, Mei S, Liu X, Luo C, O’Malley J, Gehad A, Teague J, Divito S, Fuhlbrigge R, Puigserver P, Krueger J, Hotamisligil G, Clark R, Kupper T. Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism. Nature. 2017; 543(7644):252-256.

13. Liu X, Zhang Z, Ruan J, Pan Y, Magupalli V, Wu H, and Lieberman J. Inflammasome-activated Gasdermin D causes pyroptosis by forming membrane pores. Nature. 2016; 535(7610):153-8.

14. Wittrup A, Ai A, Liu X, Hamar P, Trifonova R, Charisse K, Manoharan M, Kirchhausen T, and Lieberman J. Visualizing lipid-formulated siRNA release from endosomes and target gene knockdown. Nat Biotechnol. 2015; 33(8):870-6.

15. Wang Q*, Liu X*^#, Cui Y, Tang Y, Chen W, Li S, Yu H, Pan Y, and Wang C^#. The E3 ubiquitin ligase AMFR and INSIG1 bridge the activation of TBK1 kinase by modifying the adaptor STING. Immunity. 2014; 41(6):919-33. Cover Article.

Laboratory members:
Research Associate/Assistant: Xiwen Lou. Ph.D.; Tianchi Ma Postdoctoral Fellow: Wanyan Deng. Ph.D.; Zengzhang Zheng. Ph.D.; Wu Li. Ph.D.; Pengcheng Chen. Ph.D. Ph. D. Candidates: Yang Bai; Fan Deng; Rui Min; Ling Zhong, Zeyu Wu