General

XU Chenqi
Ph.D., Professor
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China.
Tel: 54921318
Email: cqxu@@sibcb.ac.cn


Research Areas

lymphocyte signaling


Education

1994-1998       B.S. with Honor in Biochemistry, East China Normal University

1998-2001       M.S. in Biochemistry and Molecular Biology, East China Normal University and Institute of Biochemistry  and Cell Biology, Chinese Academy of Sciences, Supervisor: Chengwu Chi, Ph.D.

2001-2004      Ph.D. in Biochemistry and Molecular Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Supervisor: Chengwu Chi, Ph.D.

2004-2009      Postdoctoral Fellow, Dana-Farber Cancer Institute, Harvard Medical School, USA, Supervisor: Kai Wucherpfennig Ph.D., M.D.


Publications

1. Bietz A#, Zhu H#, Xue M, Xu C* (2017) Cholesterol Metabolism in T Cells, Front Immunol. 8:1664

2. Yang W#, Pan W#, Chen S#, Trendel N#, Jiang S#, Xiao F, Xue M, Wu W, Peng Z, Li X, Ji H, Liu X, Jiang H, Wang H, Shen H, Dushek O*, Li H*, Xu C* (2017) Dynamic regulation of CD28 conformation and signaling by charged lipids and ions. Nat Struct Mol Biol. Published online, doi: 10.1038/nsmb.3489

3. Wang H, Wang S, Li C, Li H, Mao Y, Liu W, Xu C*, Long D* (2017) Probing Transient Release of Membrane-Sequestered Tyrosine-Based Signaling Motif by Solution NMR Spectroscopy. J Phys Chem Lett. 8(16): 3765-3769

4. Li L#, Guo X#, Shi X#, Li C#, Wu W, Yan C, Wang H, Li H, Xu C* (2017) Ionic CD3-Lck interaction regulates the initiation of T-cell receptor signaling. Proc Natl Acad Sci U S A. PLUS 114(29): E5891-E5899

5. Guo X#, Yan C#, Li H#, Huang W#, Shi X, Huang M, Wang Y, Pan W, Cai M, Li L, Wu W, Bai Y, Zhang C, Liu Z, Wang X, Zhang F X, Tang C, Wang H, Liu W, Ouyang B, Catherine C Wong, Cao Y*, Xu C* (2017) Lipid-dependent conformational dynamics underlie the functional versatility of T-cell receptor. Cell Res. 27(4): 505-525

6. Xu L#, Xia M#, Guo J#, Sun X#, Li H, Xu C, Gu X, Zhang H, Yi J, Fang Y, Xie H, Wang J, Shen Z, Xue B, Sun Y, Meckel T, Chen Y, Hu Z, Li Z*, Xu C*, Gong H*, Liu W* (2016) Impairment on the lateral mobility induced by structural changes underlies the functional deficiency of the lupus-associated polymorphism FcγRIIB-T232. J Exp Med, 213(12): 2707-2727

7. Wu W, Shi X, Xu C* (2016) Regulation of T cell signalling by membrane lipids. Nat Rev Immunol. 16(11): 690-701

8. Liu W*, Wang H, Xu C* (2016) Antigen Receptor Nanoclusters:Small Units with Big Functions. Trends Immunol. 37(10): 680-689

9. Yang W#, Bai Y#, Xiong Y, Zhang J, Chen S, Zheng X, Meng X, Li L, Wang J, Xu C ,Yan C, Wang L, Chang C, Chang T, Zhang T, Zhou P Song B, Liu W, Sun S, Liu X, Li B*, Xu C* (2016) Potentiating the anti tumour response of CD8+ T cells by modulating cholesterol metabolism. Nature. 531(7596): 651-655

10. Cui Y#, Chen X#, Zhang J, Sun X, Liu H, Bai L, Xu C, Liu X* (2016) Uhrf1 Controls iNKT Cell Survival and Differentiation through the Akt-mTOR Axis. Cell Rep. 15(2): 256-263

11. Chen X#, Pan W#, Sui Y, Li H, Shi X, Guo X, Qi H, Xu C*, Liu W* (2015) Acidic phospholipids govern the enhanced activation of IgG-B cell receptor. Nature Commun. 6(8552)

12. Liu C#, Zhao X#, Xu L, Yi J, Shaheen S, Han W, Wang F, Zheng W, Xu C, Liu W (2015) A negative-feedback function of PKCβ in the formation and accumulation of signaling-active B cell receptor microclusters within B cell immunological synapse. J Leukoc Biol. 97(5): 887-900

13. Wu W#, Yan C#, Shi X, Li L, Liu W, Xu C* (2015) Lipid in T-cell receptor transmembrane signaling. Prog Biophys Mol Biol. 118(3): 130-138

14. Wang Y#, Gao J#, Guo X#, Tong T, Shi X, Li L, Qi M, Wang Y, Cai M, Jiang J, Xu C*, Ji H*, Wang H* (2014) Regulation of EGFR nanocluster formation by ionic protein-lipid interaction. Cell Res. 24(8): 959-976

15. Li L#, Shi X#, Guo X, Li H, Xu C* (2014) Ionic protein-lipid interaction at the plasma membrane: what can the charge do? Trends Biochem Sci. 39(3): 130-140

16. Wertek F, Xu C* (2014) Digital response in T cells: to be or not to be. Cell Res. 24(3): 265-266

17. Li P, Fu Z, Zhang Y, Zhang J, Xu C, Ma Y, Li B, Song B (2014) The clathrin adaptor Numb regulates intestinal cholesterol absorption through dynamic interaction with NPC1L1. Nat Med. 20(1): 80-86

18. Shi X#, Bi Y#, Yang W#, Guo X, Jiang Y, Wan C, Li L, Bai Y, Guo J, Wang Y, Chen X, Wu B, Sun H, Liu W, Wang J*, Xu C* (2013) Ca2+ regulates T-cell receptor activation by modulating the charge property of lipids. Nature. 493(7430): 111-115

19. Liu B#, Liu Y#, Du Y, Mardaryev A, Yang W, Chen H, Xu Z, Xu C, Zhang X, Botchkarev V, Zhang Y*, Xu G* (2013) Cbx4 regulates the proliferation of thymic epithelial cells and thymus function. Development. 140(4): 780-788

20. Zhang K#, Pan Y#, Qi J, Yue J, Zhang M, Xu C, Li G*, Chen J* (2013) Disruption of disulfide-restriction at integrin knees induces activation and ligand-independent signaling of α4β7. J Cell Sci. 126(Pt21): 5030-5041,

21. Wang X#, Jimenez-Vargas J#, Xu C, Possani L*, Zhu S* (2012) Positive selection-guided mutational analysis revealing two key functional sites of scorpion ERG K(+) channel toxins. Biochem Biophys Res Commun. 429(1-2): 111-116

22. Gagnon E, Xu C, Yang W, Chu H, Call M, Chou J, Wucherpfennig K* (2010) Response multilayered control of T cell receptor phosphorylation. Cell. 142(5): 669-671

23. Xu C#, Gagnon E#, Call M, Schnell J, Schwieters C, Carman C, Chou J*, Wucherpfennig K* (2008) Regulation of T cell Receptor Activation by Dynamic Membrane Binding of the CD3e Cytoplasmic Tyrosine-Based Motif. Cell. 135(4): 702-713

24. Wang S, Huang L, Wicher D, Chi C*, Xu C* (2008) Structure-function relationship of bifunctional scorpion toxin BmBKTx1. Acta Biochim Biophys Sin (Shanghai). 40(11): 955-963

25. O’Connor K#, McLaughlin KA#, De Jager P, Chitnis T, Bettelli E, Xu C, Robinson W, Cherry S, Bar-Or A, Banwell B, Fukaura H, Fukazawa T, Tenembaum S, Wong S, Tavakoli N, Idrissova Z, Viglietta V, Rostasy K, Pohl D, Dale R, Freedman M, Steinman L, Buckle G, Kuchroo V, Hafler D*, Wucherpfennig K* (2007) Self-assembling Antigen Tetramers Permit Discrimination of Autoantibodies to Folded and Denatured Self-antigens in Demyelinating Diseases. Nat Med. 13(2): 211-217

26. Xu C, Call M, Wucherpfennig K (2006) A membrane-proximal tetracysteine motif contributes to assembly of cd3de and cd3ge dimers with the T cell receptor. J Biol Chem. 281(48): 36977-36984

27. Call M#, Schnell J#, Xu C, Lutz R, Chou J*, Wucherpfennig K* (2006) The Structure of the ζζ Transmembrane Dimer Reveals Polar Features Essential for Dimerization and Assembly with the T cell Receptor. Cell. 127(2): 355-368

28. Jiang H, Xu C, Wang C, Fan C, Zhao T, Chen J, Chi C (2006) Two novel O-superfamily conotoxins from Conus vexillum. Toxicon. 47(4): 425-436

29. Jiang H#, Wang C#, Xu C, Fan C, Dai X, Chen J, Chi C (2006) A novel M-superfamily conotoxin with a unique motif from Conus vexillum. Peptides. 27(4): 682-689

30. Xu C#, Brône B#, Wicher D, Bozkurt O, Lu W, Huys I, Han Y, Tytgat J, Van Kerkhove E, Chi C (2004) BmBKTx1, a novel Ca2+activated K+ channel blocker purified from the Asian scorpion Buthus martensi Karsch. J Biol Chem. 279(33): 34562-34569

31. Xu C, He L, Brône B, Martin-Eauclaire M, Van Kerkhove E, Zhou Z, Chi C (2004) A novel scorpion toxin blocking small conductance Ca2+ activated K+ channel. Toxicon. 43(8): 961-971

32. Cai Z#, Xu C#, Xu Y, Lu W, Chi C, Shi Y, Wu J (2004) Solution structure of BmBKTx1, a new BKCa1 channel blocker from the Chinese scorpion Buthus martensi Karsch. Biochemistry. 43(13): 3764-3771

33. Huys I#, Xu C#, Wang C, Vacher H, Martin-Eauclaire M, Chi C, Tytgat J (2004) BmTx3, a scorpion toxin with two putative functional faces separately active on A-type K+ and HERG currents. Biochem J. 378(3): 45-52

34. Frénal K#, Xu C#, Wolff N, Wecker K, Gurrola G, Zhu S, Chi C, Possani L, Tytgat J*, Delepierre M* (2004) Exploring structural features of the interaction between the scorpion toxinCnErg1 and ERG K+ channels. Proteins. 56(2): 367-375

35. Szyk A, Lu W, Xu C, Lubkowski J (2004) Structure of the Scorpion Toxin BmBKTx1 Solved from Single Wavelength Anomalous Scattering of Sulfur. J Struct Biol. 145(3): 289-294

       36. Xu C, Zhu S, Chi C, Tytgat J, Turret and pore block of K+ channels: what is the difference? (2003) Trends Pharmacol Sci. 24(9):      446-448


Patents

1.         Chinese patent, 201610015212.6, 酰基辅酶A: 胆固醇酰基转移酶ACAT1抑制剂的新用途

2.         Chinese patent, 201610015550.X, 一种提高T细胞活性的方法

3.         Chinese patent, 201610015227.2, 一种肿瘤免疫治疗药物靶点及其应用

4.         Chinese patent, 201610015548.2, 用于肿瘤免疫治疗的联合用药物组合

5.         Chinese patent, 201610015530.2, 用于肿瘤治疗的联合用药物组合

6.         International PCT, 170179PCWO, ACAT1 inhibitors for treating cancer

7.         International PCT, 170180PCWO, Activation of T cells with increased plasma membrane cholesterol levels

8.         International PCT, 170181PCWO, Combination of ACAT1 inhibitor and checkpoint antibody for treating cancer


Research Interests

To sense and fight with invading foreign pathogens or transformed self cells, mammalian immune systems develop sophisticated panels of immunoreceptors to conduct immune response and immune surveillance function. Many immunoreceptors are ideal drug targets for human diseases such as autoimmune diseases and cancers. Despite of their great clinical interest, we are still on early stage to fully understand the structure and function of immunoreceptors. The long term interest of the Xu lab is to study key immunoreceptor signaling in T cells as well as provide knowledge base for the development of better therapeutic approaches to treat human diseases. 

In 2008, we found T cell antigen receptor (TCR) phosphorylation is regulated via the dynamic interaction between TCR intracellular tyrosine motifs and plasma membrane (Xu et al, 2008). This work unveils the presence of an unexpected plasma membrane regulation to immunoreceptor activation other than the well-studied kinase-phosphatase regulation. In addition to study immunoreceptor activation mechanism, we are currently utilizing functional and structural approaches to identify and characterize new signaling proteins involved in immunoreceptor signaling and their roles in human cancers. These studies will advance our knowledge about T cell signaling as well as identify potential drug targets for treating human cancers.


Conferences

2017                Annual Meeting of American Association of Immunologists, Washington, USA

2017                Department of Biochemistry and Biophysics, University of California, San Francisco, USA

2017                Section of Cell and Developmental Biology, University of California, San Diego, USA

2017                Memorial Sloan Kettering Cancer Center, New York, USA

2017                Department of Chemistry, University of Illinois at Chicago, USA

2017                The Ben May Department for Cancer Research, University of Chicago, USA

2017                Cold Spring Harbor Asia conference “Cell signaling & metabolism in development & diseasess”, Suzhou (co-                            organizer)

2017                The 11th National Congress of Biophysics, Shanghai

2017                Xiangshan Science Conferences “Metabolic Regulation”, Beijing

2017                The 13th Military Immunology Conference, Nanjing

2016                The 5th Chinese-German Symposium on Immunology and the second Meeting of Sino-German Cooperation                                Group “Tumor Immunology”, Dresden, German

2016                BIOSS Center, Freiburg University, Freiburg, German

2016                The 11th National Congress of Biochemistry and Molecular Biology, Hangzhou

2016                Chinese Structure Biology Symposium, Shenzhen

2016                The 23rd East Asia Joint Symposium, the 15th Cross-Strait Symposium on Biomedical Research and the 13th                              Symposium of the Frontiers of Biomedical Sciences, Taiwan

2016                The Second Trilateral Workshop on Frontier Protein Studies, Osaka, Japan

2016                EMBO Conference "Lymphocyte Antigen Receptor Signaling", Siena, Italy

2015                The 6th Asia-Pacific NMR Symposium (APNMR), Hongkong

2015                Department of Biochemistry, University of Oxford, UK

2015                The 4th European Congress of Immunology, Vienna, Austria

2015                The 10th National Congress of Biophysics, Kunming

2015                The 5th National Symposium on "Interdisciplinary Protein Research", Jining

2014                FASEB Science Research Conference “Immunoreceptors”, Colorado, USA

2014                International Lipidall Symposium, Beijing

2014                Cold Spring Harbor Asia conference “Mechanisms of Transmembrane Signaling”, Suzhou

2014                Department of Biochemistry and Biophysics, University of California, San Francisco, USA

2014                The 1st National Bio-NMR Conference, Kunming

2013                National Institute of Material Sciences, Japan

2013                Annual Meeting for the Japanese Society for Immunology, Makuhari, Japan

2013                The 14th SCBA International Symposium, Xi’an

2013                The 9th National Congress of Biophysics, Nanchang

2013                Shanghai Immunology Symposium, Wuzheng

2013                Division of Life Science, The Hong Kong University of Science & Technology, Hongkong

2013                Annual Meeting of American Association of Immunologists, Hawaii, USA

2013                Cold Spring Harbor Asia Conference “Membrane protein structure and function”, Suzhou

2013                National Congress of Cell Biology, Wuhan

2013                Chinese structure biology symposium, Chongqing

2013                Wuhan University, Wuhan

                         2013                 The 4th National Symposium on "Interdisciplinary Protein Research", Hefei


Students

已指导学生

杨魏  博士研究生  071010-生物化学与分子生物学  

蒋燕  硕士研究生  071010-生物化学与分子生物学  

郭兴东  博士研究生  071010-生物化学与分子生物学  

施小山  博士研究生  071010-生物化学与分子生物学  

李伦乙  硕士研究生  430139-生物工程  

王英芳  硕士研究生  085238-生物工程  

张瑾  博士研究生  071010-生物化学与分子生物学  

潘炜铃  硕士研究生  085238-生物工程  

陈硕凯  硕士研究生  085238-生物工程  

李昌庭  硕士研究生  085238-生物工程  

现指导学生

郭俊  博士研究生  071010-生物化学与分子生物学  

孟祥波  博士研究生  071010-生物化学与分子生物学  

闫成松  博士研究生  071010-生物化学与分子生物学  

白轶冰  博士研究生  071010-生物化学与分子生物学  

吴微  博士研究生  071010-生物化学与分子生物学  

薛蛮蛮  硕士研究生  085238-生物工程  

何星  博士研究生  071010-生物化学与分子生物学  

朱珩毓   硕士研究生  071010-生物化学与分子生物学  

周秋萍  博士研究生  071010-生物化学与分子生物学  

姜书谭  博士研究生  071010-生物化学与分子生物学  

刘希伟  博士研究生  071010-生物化学与分子生物学  

Honors & Distinctions

2017                Top Ten Breakthroughs of Chinese Science of Year 2016

2017                Top Ten Breakthroughs of Chinese Life Science of Year 2016

2017                VCANBIO Award for Biological Science and Medicine

2016                National Distinguished Scientific and Technical Workers

2016                Shanghai Youth Award for Science and Technology

2016                Tan Jiazhen Life Science Innovation Award

2015                Shanghai Academic Leader Program

2015                Ten Thousand Talent Program “National Program for Support of Top-notch Young Professionals” of China (万人计划“青年拔尖人才”)

2014                Distinguished Research Paper Award of Chen-Lu Tsou Foundation

2014                “Excellence” in the Final Review of CAS Hundred Talent Program

2014                Distinguished Life Science Award of Meiji

2014                Distinguished Young Scholar Program, National Science Foundation of China (基金委杰青)

2013                CAS Outstanding Mentor Award

2013                Chinese Journal of Cell Biology - Cell Signaling Technology Outstanding Researcher Award of Cell Biology

2013                CAS Young Scientist Award

                           2010                      CAS Hundred Talent Program (中科院****)