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  • 陈剑峰
  • 研究员,研究组长,博士生导师
  • E-mail: jfchen@@sibcb.ac.cn
  • 实验室主页: 
    个人简介:
  •   1996年6月毕业于复旦大学微生物系,获得理学学士学位;2001年5月毕业于中国科学院上海生物化学研究所,获得理学博士学位;2001年9月至2007年1月在美国哈佛医学院,CBR生物医学研究所(The CBR Institute for Biomedical Research, Harvard Medical School)从事博士后研究;2007年1月起任中国科学院上海生物化学与细胞生物学研究所研究员,研究组长。

    社会任职:
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    研究方向:
  • 炎症与癌症中细胞粘附分子的功能调控
    研究工作:
  •   在炎症与癌症的病理过程中,淋巴细胞与癌细胞的运动是其中的关键步骤。而决定这些细胞运动的一类重要分子是细胞粘附分子(Cell Adhesion Molecule,CAM),其中整合素(integrin)家族是最重要的一类粘附分子。在细胞运动的过程中,整合素的功能受到动态的、精确的调控。而病理条件下的整合素功能会发生紊乱。我们的研究兴趣点是与炎症和癌症相关的整合素的功能调控及其分子机制,了解整合素在炎症细胞迁移与癌细胞发生、发展和转移过程中的作用机制,寻找炎症与癌症的新疗法。通过研究细胞粘附分子与其配体的识别、结合及其所介导的信号转导,找到调控细胞粘附分子功能的关键点,进而通过控制细胞粘附分子的功能而达到治疗炎症与癌症的目的。

      本实验室的主要研究方向包括:

      1、整合素在免疫细胞运动中的作用机制及其自身免疫疾病中的作用机理;

      2、免疫细胞与肠道干细胞和菌群的互作及其在肠道稳态中的作用机理;

      3、整合素及趋化因子在肿瘤免疫中的作用机制;

      4、整合素在肿瘤发生、发展与转移中的作用机制;

      5、以整合素为靶的药物筛选以及肿瘤的早期诊断方法。

    承担科研项目情况:
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    代表论著:
    1. Chen SY#, Zheng YJ#, Ran XJ#, Du H, Feng H, Yang L, Wen Y, Lin CD, Wang SH, Huang MW, Yan ZJ, Wu D, Wang HY, Ge GX, Zeng A*, Zeng YA*, Chen JF*. Integrin αEβ7+ T cells direct intestinal stem cell fate decisions via adhesion signaling. Cell Res (2021), doi:10.1038/s41422-021-00561-2.
    2. Lin CD#, Li Y#, Zhang YB#. Liu ZY, Mu X, Gu CJ, Liu J, Li YT, Li GH*, Chen JF*. Ceftazidime is a potential drug to inhibit SARS-CoV-2 infection in vitro by blocking spike protein-ACE2 interaction. Signal Transduct Tar (2021), 6: 198.
    3. Wang S#, Lin CD#, Li Y, Liu ZY, Wang JL, Zhang YH, Yan ZJ, Zhang YB*, Li GH*, Chen JF*. Distinct chemokines selectively induce HIV-1 gp120-integrin α4β7 binding via triggering conformer-specific activation of α4β7. Signal Transduct Tar (2021), 6: 265.
    4. Yuan MY#, Wan YY#, Liu C#, Li Y, Liu ZY, Lin CD*, Chen JF*. Identification and characterization of a monoclonal antibody blocking the SARS-CoV-2 spike protein-ACE2 interaction. Cell Mol Immunol (2021), 18:1562-1564.
    5. Zhang YH#, Xie RT#, Zhang HL#, Zheng YJ, Lin CD, Yang L, Huang MW, Song FF, Lu L, Yang MQ, Liu Y, Wei Q*, Li JY*, Chen JF*. Integrin β7 inhibits colorectal cancer pathogenesis via maintaining the anti-tumor immunity. Cancer Immunol Res (2021), 9:967-980.
    6. Lin CD*, Liu ZY, Li Y, Chen JF*. Fever-range whole-body hyperthermia treatment of mice and the evaluation of T cell adhesion and transmigration. STAR Protocols (2021), 2: 100720.
    7. Yuan MY#, Yang YR#, Li Y, Yan ZJ, Lin CD*, Chen JF*. Mucin-Like Domain of Mucosal Addressin Cell Adhesion Molecule-1 Facilitates Integrin α4β7-Mediated Cell Adhesion Through Electrostatic Repulsion. Front. Cell Dev. Biol. (2020), 8: 603148.
    8. Zhang HL#, Zheng YJ#,*, Pan YD#, Lin CD, Wang SH, Yan ZJ, Lu L, Ge GX, Li JS, Zeng YA, Chen JF*. A mutation that blocks integrin α4β7 activation prevents adaptive immune-mediated colitis without increasing susceptibility to innate colitis. BMC Biol. (2020) 18(1):64.
    9. Zheng YJ#, Fang ZY#, Xue Y#, Zhang J, Zhu JJ, Gao RY, Yao S, Ye Y, Wang SH, Lin CD, Chen SY, Huang H, Hu L, Jiang GN, Qin HL, Zhang P*, Chen JF*, Ji HB*. Specific gut microbiome signature predicts the early-stage lung cancer. Gut Microbes (2020), 11:4, 1030-1042.
    10. Lin CD#, Zhang YH#, Zhang K, Zheng YJ, Lu L, Chang HS, Yang H, Yang YR, Wan YY, Wang SH, Yuan MY, Yan ZJ, Zhang RG, He YN, Ge GX, Wu D, Chen JF*. Fever Promotes T Lymphocyte Trafficking via a Thermal Sensory Pathway Involving Heat Shock Protein 90 and α4 Integrins. Immunity (2019), 50(1): 137-151.  
      Research Highlights in Nature (2019) 565: 400.
      Research Highlights in Science (2019) 363: 596.
      Research Highlights in Nat Rev Immunol (2019) 19: 139.
      News & Analysis in JAMA (2019) 321: 1657-1658.
      News in Cell, Jan. 15, 2019
    11. Lin CD, Chen JF*. Regulation of immune cell trafficking by febrile temperatures, Int. J. Hyperthermia (2019), 36:sup1, 17-21. (invited review)
    12. Guo J#, Zhang YH#, Li H#, Chu HY#, Wang QS, Jiang ST, Li Y, Shen HB, Li GH*, Chen JF*, Xu CQ* Intramembrane ionic protein-lipid interaction regulates integrin structure and function. PLoS Biol, (2018), 16(11): e2006525.
    13. Wang SH, Wu CY, Zhang YB, Zhong QL, Sun H, Cao WP, Ge GX, Li GH*, Zhang XF*, Chen JF*. Integrin α4β7 switches its ligand specificity via distinct conformer-specific activation. J Cell Biol. (2018), 217(8): 2799-2812.
    14. Guo QM#, Wang JL#, Xiao JF, Wang L, Hu XM, Yu WJ, Song G, Lou JT*, Chen JF*. Heterogeneous mutation pattern in tumor tissue and circulating tumor DNA warrants parallel NGS panel testing. Mol Cancer (2018), 17(1):131.
    15. Yan ZJ#, Pan YD#, Wang SH#, Cheng MH, Kong HM, Sun CG, Hu K, Chen TL, Dong QR, Chen JF*. Static compression induces ECM remodeling and integrin α2β1 expression and signaling in a rat tail caudal intervertebral disc degeneration model. Spine (2017), 42(8): E448-E458.
    16. Zhang YH#, Pan YD#, Lin CD#, Zheng YJ, Sun H, Zhang HL, Wang JL, Yuan MY, Duan T*, Du QL*, Chen JF*. Bile acids evoke placental inflammation by activating Gpbar1/NF-κB pathway in intrahepatic cholestasis of pregnancy. J Mol Cell Biol. (2016),8(6):530-541.
    17. Lu L#, Lin CD#, Yan ZJ, Wang S, Zhang YH, Wang SH, Wang JL, Liu C, Chen JF*. Kindlin-3 is essential for resting α4β1 integrin-mediated firm cell adhesion under shear flow conditions J Biol Chem. (2016), 291(19): 10363-71.
    18. Zhang HL#, Zheng YJ#, Pan YD, Xie C, Sun H, Zhang YH, Yuan MY, Song BL, Chen JF*. Regulatory T-cell depletion in the gut caused by integrin β7 deficiency exacerbates DSS colitis by evoking aberrant innate immunity. Mucosal Immunol. (2015),9(2): 391-400.
    19. Du QL#, Pan YD#, Zhang YH#, Zhang HL, Zheng YJ, Lu L, Wang JL, Duan T*, Chen JF*. Placental gene-expression profiles of intrahepatic cholestasis of pregnancy reveal involvement of multiple molecular pathways in blood vessel formation and inflammation. BMC Med Genomics (2014), 7:24.
    20. Sun H#, Liu J#, Zheng YJ, Pan YD, Zhang K, Chen JF*. Distinct chemokine signaling regulates integrin ligand specificity to dictate tissue-specific lymphocyte homing. Dev Cell (2014), 30(1): 61-70. (Cover Story).
    21. Liu J#, Fu T#, Peng B, Sun H, Li GH*, Chen JF*. The Hydrophobic Contacts Between the Center of the βI Domain and the α1/α7 Helices are Crucial for the Low-Affinity State of Integrin α4β7. FEBS J. (2014), 281: 2519-26.
    22. Zhang K#, Pan YD#, Qi JP, Yue J, Zhang MB, Xu CQ, Li GH*, Chen JF*. Disruption of disulfide-restriction at integrin knees induces activation and ligand-independent signaling of α4β7. J Cell Sci. (2013), 126:5030-41.
    23. Yue J#, Pan YD#, Sun LF, Zhang K, Liu J, Lu L, Chen JF*. The unique disulfide bond-stabilized W1 β4-β1 loop in α4 β-propeller domain regulates integrin α4β7 affinity and signaling. J Biol Chem. (2013), 288(20): 14228-37.
    24. Qi JP#, Zhang K#, Zhang Q, Sun Y, Fu T, Li GH, Chen JF*. Identification, characterization and epitope mapping of a human monoclonal antibody J19 that specifically recognizes the activated integrin α4β7. J Biol Chem. (2012), 287(19): 15749-59.
    25. Yue J, Zhang K, Chen JF*. Role of integrins in regulating proteases to mediate extracellular matrix remodeling. Cancer Microenviron. (2012), 5(3):275-83. (invited review)
    26. Zhang K, Chen JF*. The regulation of integrin function by divalent cations. Cell Adhes Migr. (2012), 6 (1): 1–10. (invited review)
    27. Sun H, Wu YM, Qi JP, Pan YD, Ge GX, Chen JF*. The CC' and DE loops in Ig domains 1 and 2 of MAdCAM-1 play different roles in MAdCAM-1 binding to low- and high-affinity integrin α4β7. J Biol Chem(2011), 286(14): 12086-92.
    28. Pan YD, Zhang K, Qi JP, Yue J, Springer TA*, Chen JF*. Cation-π interaction regulates ligand-binding affinity and signaling of integrin α4β7. Proc. Natl. Acad. Sci. U. S. A. (2010), 107: 21388-93.
    29. Chen JF#, Yang W#, Kim M, Carman CV, Springer TA*. Regulation of Outside-In Signaling and Affinity by the β I domain of Integrin αLβ2. Proc. Natl. Acad. Sci. U. S. A. (2006), 103:13062-67.
    30. Chen JF, Takagi J, Xie C, Xiao T, Luo BH, Springer TA*. The relative influence of metal ion binding sites in the I-like domain and the interface with the hybrid domain on rolling and firm adhesion by integrin α4β7. J Biol Chem. (2004), 279: 55556-61.
    31. Chen JF, Salas A, Springer TA*. Bistable regulation of integrin adhesiveness by a bipolar metal ion cluster. Nature Struct Biol. (2003), 10(12): 995-1101.
    32. Xu MG#Chen JF#, Martin F, Zhao MW, Eriani G, Wang ED. Leucyl-tRNA synthetase consisting of two subunits from hyperthermophilic bacteria Aquifex aeolicus. J Biol Chem. (2002), 277(44): 41590-96.
    33. Chen JF, Li T, Wang ED, Wang YL. The Effect of Alanine-293 Replacement on the Activity, ATP-Binding, and Editing of E. coli Leucyl-tRNA Synthetase. Biochemistry (2001), 40(5): 1144-9.
    34. Chen JF, Guo NN, Li T, Wang ED, Wang YL. CP1 domain in Escherichia coli leucyl-tRNA synthetase is crucial for its editing function. Biochemistry (2000), 39(22): 6726-31.
    35. Chen JF, Li Y, Wang E, Wang Y. High-level expression and single-step purification of leucyl-tRNA synthetase from Escherichia coliProtein Expres Purif. (1999), 15(1): 115-20. 
    36. Chen JF, Li Y, Jiang WH, Yang YL, Zhao GP, Wang ED. Secretory Expression of GL-7-ACA Acylase in E. coliActa Biochimica et Biophysica Sinica. (1998), 30(4): 393-6.
    获奖及荣誉:
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    研究组成员:
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