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Faculty

Members of CAS, CAE
National Outstanding Young Scientists Award
Principal Investigators
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Address: 320 Yue Yang Road, Shanghai 200031, P.R. China
Tel: 86-21-54920000
Fax: 86-21-54921011
Email: sibcb@sibs.ac.cn
Website: www.sibcb.ac.cn
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Principal Investigators
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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.
Email: cqxu@@sibcb.ac.cn
Lab homepage: xulab.sibcb.ac.cn

Research Areas
lymphocyte and disease

Research Interests

T cells are key players in the immune system to fight against invading pathogens and tumor cells. T-cell based immunotherapies have been successfully applied in clinic to treat cancers and other diseases. However, the current therapies have limited efficacy so that more mechanistic studies of T cell biology are urged to pave the way for developing new concepts of immunotherapies. We study both T-cell signaling and metabolism, aiming to understand the basic rules of adaptive immunity and to develop new means of cancer immunotherapy.
In the past years, the Xu lab has developed cutting-edge biochemical and biophysical technologies to study transmembrane signaling of T-cell receptor, co-stimulatory and co-inhibitory receptors. These basic studies lead to better understanding of the fundamental feature of T cell immunity, i.e. high sensitivity and specificity. More recently, we become interested in T-cell lipid metabolism and demonstrate that modulation of T-cell lipid metabolism represents a new direction of cancer immunotherapy. In the next five years, the Xu lab will mainly focus on the following subjects.
1.      Lipid metabolic programs of T-cell subsets under different physiological and pathological conditions.
2.      Functional roles of lipid metabolism in T-cell antitumor immunity.
3.      Identification of T-cell °įmetabolic checkpoints°Ī for cancer immunotherapy.
4.      Development of new tools such as state-of-art Mass Spectrometry to study TCR, CD28 and PD-1 signaling.

Selected Publications

( #first author, *corresponding author )
  1. Xu C, Xie H, Guo X, Gong H, Liu L, Qi H, Xu C, Liu W*. A PIP2-derived amplification loop fuels the sustained initiation of B cell activation. Science Immunology, 2(17), 2017
  2. Bietz A#, Zhu H#, Xue M, Xu C*. Cholesterol Metabolism in T Cells. Frontiers in Immunology, 8:1664, 2017
  3. 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*. Dynamic regulation of CD28 conformation and signaling by charged lipids and ions. Nature Structural & Molecular Biology, 24(12), pp 1081-1092, 2017.
  4. Wang H, Wang S, Li C, Li H, Mao Y, Liu W, Xu C*, Long D*. Probing Transient Release of Membrane-Sequestered Tyrosine-Based Signaling Motif by Solution NMR Spectroscopy. The Journal of Physical Chemistry Letters, 8(16), pp 3765-3769, 2017.
  5. Li L#, Guo X#, Shi X#, Li C#, Wu W, Yan C, Wang H, Li H, Xu C*, Ionic CD3-Lck interaction regulates the initiation of T-cell receptor signaling. Proc Natl Acad Sci U S A, 2017, (in press).
  6. 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*, Lipid-dependent conformational dynamics underlie the functional versatility of T-cell receptor. Cell Research, 27(4), pp 505-525, 2017.
  7. 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*, Impairment on the lateral mobility induced by structural changes underlies the functional deficiency of the lupus-associated polymorphism Fc¶√RIIB-T232. The Journal of Experimental Medicine, 213(12), pp 2707-2727, 2016.
  8. Wu W, Shi X, Xu C*, Regulation of T cell signalling by membrane lipids. Nature Reviews Immunology, 16(11), pp 690-701, 2016.
  9. Liu W*, Wang H, Xu C*, Antigen Receptor Nanoclusters:Small Units with Big Functions. Trends in Immunology, 37(10), pp 680-689, 2016.
  10. 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*, Potentiating the anti tumour response of CD8+ T cells by modulating cholesterol metabolism. Nature, 531(7596), pp 651-655, 2016.
  11. Cui Y#, Chen X#, Zhang J, Sun X, Liu H, Bai L, Xu C, Liu X*, Uhrf1 Controls iNKT Cell Survival and Differentiation through the Akt-mTOR Axis. Cell Reports, 15, pp 256-263, 2016.
  12. Chen X#, Pan W#, Sui Y, Li H, Shi X, Guo X, Qi H, Xu C*, Liu W*, Acidic phospholipids govern the enhanced activation of IgG-B cell receptor. Nature Communications, 6(8552), 2015.
  13. Liu C#, Zhao X#, Xu L, Yi J, Shaheen S, Han W, Wang F, Zheng W, Xu C, Liu W, A negative-feedback function of PKC¶¬ in the formation and accumulation of signaling-active B cell receptor microclusters within B cell immunological synapse. Journal of Leukocyte Biology, 97(5), pp 887-900, 2015.
  14. Wu W#, Yan C#, Shi X, Li L, Liu W, Xu C*, Lipid in T-cell receptor transmembrane signaling. Progress in Biophysics and Molecular Biology 118(3), pp 130-138, 2015.
  15. 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*, Regulation of EGFR nanocluster formation by ionic protein-lipid interaction. Cell Research, 24(8), pp 959-976, 2014.
  16. Li L#, Shi X#, Guo X, Li H, Xu C*, Ionic protein-lipid interaction at the plasma membrane: what can the charge do? Trends in Biochemical Sciences, 39(3), pp 130-140, 2014.
  17. Wertek F, Xu C*, Digital response in T cells: to be or not to be. Cell Research, 24(3), pp 265-266, 2014.
  18. Li P, Fu Z, Zhang Y, Zhang J, Xu C, Ma Y, Li B, Song B, The clathrin adaptor Numb regulates intestinal cholesterol absorption through dynamic interaction with NPC1L1. Nature Medicine, 20(1), pp 80-86, 2014.
  19. 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*, Ca2+ regulates T-cell receptor activation by modulating the charge property of lipids. Nature, 493(7430), pp 111-115, 2013.
  20. Liu B#, Liu Y#, Du Y, Mardaryev A, Yang W, Chen H, Xu Z, Xu C, Zhang X, Botchkarev V, Zhang Y*, Xu G*, Cbx4 regulates the proliferation of thymic epithelial cells and thymus function. Development, 140(4), pp 780-788, 2013.
  21. Zhang K#, Pan Y#, Qi J, Yue J, Zhang M, Xu C, Li G*, Chen J*, Disruption of disulfide-restriction at integrin knees induces activation and ligand-independent signaling of ¶Ń4¶¬7. Journal of Cell Science, 126(Pt21), pp 5030-5041, 2013.
  22. Wang X#, Jimenez-Vargas J#, Xu C, Possani L*, Zhu S*, Positive selection-guided mutational analysis revealing two key functional sites of scorpion ERG K(+) channel toxins. Biochemical and Biophysical Research Communications, 429(1-2), pp 111-116, 2012.
  23. Gagnon E, Xu C, Yang W, Chu H, Call M, Chou J, Wucherpfennig K*, Response multilayered control of T cell receptor phosphorylation. Cell, 142(5), pp 669-671, 2010.
  24. Xu C#, Gagnon E#, Call M, Schnell J, Schwieters C, Carman C, Chou J*, Wucherpfennig K*, Regulation of T cell Receptor Activation by Dynamic Membrane Binding of the CD3e Cytoplasmic Tyrosine-Based Motif. Cell, 135(4), pp 702-713, 2008.
  25. Wang S, Huang L, Wicher D, Chi C*, Xu C*, Structure-function relationship of bifunctional scorpion toxin BmBKTx1. Acta Biochimica et Biophysica Sinica (Shanghai), 40(11), pp 955-963, 2008.
  26. O°ĮConnor 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*, Self-assembling Antigen Tetramers Permit Discrimination of Autoantibodies to Folded and Denatured Self-antigens in Demyelinating Diseases. Nature Medicine, 13(2), pp 211-217, 2007.
  27. Xu C, Call M, Wucherpfennig K, A membrane-proximal tetracysteine motif contributes to assembly of cd3de and cd3ge dimers with the T cell receptor. Journal of Biological Chemistry, 281(48), pp 36977-36984, 2006.
  28. Call M#, Schnell J#, Xu C, Lutz R, Chou J*, Wucherpfennig K*, The Structure of the ¶∆¶∆ Transmembrane Dimer Reveals Polar Features Essential for Dimerization and Assembly with the T cell Receptor. Cell, 127(2), pp 355-368, 2006.
  29. Jiang H, Xu C, Wang C, Fan C, Zhao T, Chen J, Chi C, Two novel O-superfamily conotoxins from Conus vexillum. Toxicon, 47(4), pp 425-436, 2006.
  30. Jiang H#, Wang C#, Xu C, Fan C, Dai X, Chen J, Chi C, A novel M-superfamily conotoxin with a unique motif from Conus vexillum. Peptides, 27(4), pp 682-689, 2006.
  31. Xu C#, Brône B#, Wicher D, Bozkurt O, Lu W, Huys I, Han Y, Tytgat J, Van Kerkhove E, Chi C, BmBKTx1, a novel Ca2+activated K+ channel blocker purified from the Asian scorpion Buthus martensi Karsch. Journal of Biological Chemistry, 279(33), pp 34562-34569, 2004.
  32. Xu C, He L, Brône B, Martin-Eauclaire M, Van Kerkhove E, Zhou Z, Chi C, A novel scorpion toxin blocking small conductance Ca2+ activated K+ channel. Toxicon, 43(8), pp 961-971, 2004.
  33. Cai Z#, Xu C#, Xu Y, Lu W, Chi C, Shi Y, Wu J, Solution structure of BmBKTx1, a new BKCa1 channel blocker from the Chinese scorpion Buthus martensi Karsch. Biochemistry, 43(13), pp 3764-3771, 2004.
  34. Huys I#, Xu C#, Wang C, Vacher H, Martin-Eauclaire M, Chi C, Tytgat J, BmTx3, a scorpion toxin with two putative functional faces separately active on A-type K+ and HERG currents. Biochemical Journal, 378(3), pp 45-52, 2004.
  35. Fr®¶nal K#, Xu C#, Wolff N, Wecker K, Gurrola G, Zhu S, Chi C, Possani L, Tytgat J*, Delepierre M*, Exploring structural features of the interaction between the scorpion toxinCnErg1 and ERG K+ channels. PROTEINS: Structure, Function, and Bioinformatics, 56(2), pp 367-375, 2004.
  36. Szyk A, Lu W, Xu C, Lubkowski J, Structure of the Scorpion Toxin BmBKTx1 Solved from Single Wavelength Anomalous Scattering of Sulfur. Journal of Structural Biology, 145(3), pp 289-294, 2004.
  37. Xu C, Zhu S, Chi C, Tytgat J, Turret and pore block of K+ channels: what is the difference? Trends in Pharmacological Sciences, 24(9), pp 446-448, 2003.

Education Background & Academic Experience
Nov. 2009- present, Principle Investigator, Institute of Biochemistry and Cell Biology, SIBS
Apr.-Sep. 2009, Instructor, Dana-Farber Cancer Institute, Harvard Medical School
Aug. 2004-Mar. 2009, Postdoctoral Fellow, Dana-Farber Cancer Institute, Harvard Medical School
Jul. 2004, Ph.D. Institute of Biochemistry and Cell Biology, SIBS

Research Team

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