Professor, “Hundred Talents Program”, CAS
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.
*first author, #corresponding author
1. Li L#，Shi X#，Guo X，Li H，Xu C*，Ionic protein–lipid interaction at theplasma membrane: what can the charge do?，Trends in Biochemical Sciences，39(3)，pp 130-140，2014
Wertek F，Xu C，Digital response in T cells: to be or not to be，Cell Research 24(3)，pp 265-266，2014.
2. 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
3. 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 α4β7，Journal of Cell Science，126(21)，pp 5030-5041，2013
4. 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, 2013. 493: 111-5.
5. Liu B, Liu YF, Du YR, Mardaryev AN, Yang W, Chen H, Xu ZM, Xu CQ, Zhang XR, Botchkarev VA, Zhang Y, Xu GL. Cbx4 regulates the proliferation of thymic epithelial cells and thymus function. Development. 2013. 140: 780-8.
6. Wang X, Jimenez-Vargas JM, Xu C, Possani LD, Zhu S. Positive selection-guided mutational analysis revealing two key functional sites of scorpion ERG K(+) channel toxins. Biochem Biophys Res Commun. 2012. 429: 111-6.
7. Gagnon E, Xu C, Yang W, Chu HH, Call ME, Chou JJ, Wucherpfennig KW. Response multilayered control of T cell receptor phosphorylation. Cell. 2010. 142: 669-71.
8. Xu C*, Gagnon E*, Call ME, Schnell JR, Schwieters CD, Carman CV, Chou JJ, Wucherpfennig KW. Regulation of T cell Receptor Activation by Dynamic Membrane Binding of the CD3e Cytoplasmic Tyrosine-Based Motif. Cell. 2008. 135: 702-713
9. Wang S, Huang L, Wicher D, Chi C#, Xu C#. Structure-function relationship of bifunctional scorpion toxin BmBKTx1. Acta Biochim Biophys Sin (Shanghai). 2008. 40: 955-63.
10. Xu C, Call ME, Wucherpfennig KW. A membrane-proximal tetracysteine motif contributes to assembly of cd3de and cd3ge dimers with the T cell receptor. Journal of Biological Chemistry. 2006. 281: 36977-84
11. O’Connor KC*, McLaughlin KA*, De Jager PL, Chitnis T, Bettelli E, Xu C, Robinson WH, Cherry SV, Bar-Or A, Banwell B, Fukaura H, Fukazawa T, Tenembaum S, Wong SJ, Tavakoli NP, Idrissova Z, Viglietta V, Rostasy K, Pohl D, Dale RC, Freedman M, Steinman L, Buckle GJ, Kuchroo VK, Hafler DA, Wucherpfennig KW. Self-assembling Antigen Tetramers Permit Discrimination of Autoantibodies to Folded and Denatured Self-antigens in Demyelinating Diseases. Nature Medicine. 2007. 13: 211-7
12. Call ME*, Schnell JR*, Xu C, Lutz RA, Chou JJ, Wucherpfennig KW. The Structure of the ζζ Transmembrane Dimer Reveals Polar Features Essential for Dimerization and Assembly with the T cell Receptor. Cell. 2006. 127: 355-68
13. Jiang H, Xu C, Wang CZ, Fan CX, Zhao TY, Chen JS, Chi CW. Two novel O-superfamily conotoxins from Conus vexillum. Toxicon. 2006. 47: 425-36
14. Jiang H, Wang CZ, Xu C, Fan CX, Dai XD, Chen JS, Chi CW. A novel M-superfamily conotoxin with a unique motif from Conus vexillum. Peptides. 2006. 27: 682-9
15. Xu C*, Brône B*, Wicher D, Bozkurt O, Lu WY, Huys I, Han YH, Tytgat J, Van Kerkhove E, Chi CW. BmBKTx1, a novel Ca2+-activated K+ channel blocker purified from the Asian scorpion Buthus martensi Karsch. Journal of Biological Chemistry. 2004. 279: 34562-9
16. Xu C, He LL, Brône B, Martin-Eauclaire MF, Van Kerkhove E, Zhou Z, Chi CW. A novel scorpion toxin blocking small conductance Ca2+ activated K+ channel. Toxicon. 2004. 43: 961-71
17. Cai Z*, Xu C*, Xu Y, Lu W, Chi CW, Shi Y, Wu J. Solution structure of BmBKTx1, a new BKCa1 channel blocker from the Chinese scorpion Buthus martensi Karsch. Biochemistry. 2004. 43: 3764-71
Huys I*, Xu C*, Wang CZ, Vacher H, Martin-Eauclaire MF, Chi CW, Tytgat J. BmTx3, a scorpion toxin with two 18. putative functional faces separately active on A-type K+ and HERG currents. Biochemical Journal. 2004. 378: 745-52
19. Frénal K*, Xu C*, Wolff N, Wecker K, Gurrola GB, Zhu SY, Chi CW, Possani LD, Tytgat J, Delepierre M. Exploring structural features of the interaction between the scorpion toxinCnErg1 and ERG K+ channels. PROTEINS: Structure, Function, and Bioinformatics. 2004. 56: 367-75
20. Szyk A, Lu WY, Xu C, Lubkowski J. Structure of the Scorpion Toxin BmBKTx1 Solved from Single Wavelength Anomalous Scattering of Sulfur. Journal of Structural Biology. 2004. 145: 289-94
21. Xu C, Zhu SY, Chi CW, Tytgat J. Turret and pore block of K+ channels: what is the difference? TRENDS in Pharmacological Sciences. 2003. 24: 446-8
22. 施小山, 许琛琦. “小离子的大功能”—钙离子调控T细胞抗原受体活化的机制研究. 中国细胞生物学学报. 2013. 35: 115-8
23. 施小山, 李伦乙, 郭兴东, 许琛琦. T细胞抗原受体的结构与功能研究进展. 中国细胞生物学学报. 2011. 33: 955-63
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