
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
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****)