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Faculty

Members of CAS, CAE
National Outstanding Young Scientists Award
Principal Investigators
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
Principal Investigators
CHEN Jianfeng
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: jfchen@@sibcb.ac.cn

Research Areas
Cell adhesion molecules, integrin, affinity, signaling, inflammation, cancer, metastasis,drug discovery

Research Interests
The research interests of our group focus on the cell adhesion molecules. We try to understand the mechanism and biological function of integrin-ligand interaction and its bidirectional signal transduction across plasma membrane.
Integrins are a family of heterodimeric cell adhesion molecules with noncovalently associated  and  subunits that mediate cell-cell, cell-matrix and cell-pathogen interactions. They play vital roles in the pathogenesis of many human diseases. We mainly work on three integrins: 47, 41 and 64. Integrin 47 and 41 are lymphocyte homing receptors which can mediate both rolling and firm adhesion of lymphocyte on their ligands. 4 integrins have been implicated in many inflammatory diseases, such as Crohn´s disease, ulcerative colitis and multiple sclerosis. Integrin 64 maintains the integrity of epithelia through hemidesmosomes, which has been implicated in carcinoma metastasis.
All of the biological functions of integrins rely on their interaction with ligands and associated signaling. Understanding of the mechanism of the dynamic regulation of integrin-ligand interaction and its signaling is critical for finding new therapeutics for the above diseases. We use wide range of techniques to addressing the following questions: How integrin control its interaction to ligand? How is the integrin conformation before, during and after ligand binding? How the ligand binding transfers signal into the cells and trigger the intracellular signaling pathway? What happened in the cells after integrin is activated? How integrin is activated by intracellular signals? How integrin is activated to recognize different ligands? In addition, we are also interested in generating antibodies targeting integrins for therapeutics.

Selected Publications

  1. Lin CD, ZhangYH, 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, and Chen JF*. Fever Promotes T Lymphocyte Trafficking via a Thermal Sensory Pathway Involving Heat Shock Protein 90 and 4 Integrins. Immunity (2019), 50(1): 137-151.
  2. Guo J, Zhang Y, Li H, Chu H, Wang Q, Jiang S, Li Y, Shen H, Li G*, Chen JF*, Xu C* Intramembrane ionic protein-lipid interaction regulates integrin structure and function. PLoS Biol, (2018), 16(11): e2006525.
  3. Wang SH, Wu C, Zhang CY, Zhong QL, Sun H, Cao WP, Ge GX, Li GH*, Zhang XF*, Chen JF*. Integrin 47 switches its ligand specificity via distinct conformer-specific activation. J Cell Biol. (2018), 217(8): 2799-2812.
  4. Guo Q, Wang J, Xiao J,  Wang L, Hu X, Yu W, Song G, Lou J*, Chen JF*. Heterogeneous mutation pattern in tumor tissue and circulating tumor DNA warrants parallel NGS panel testing. Mol Cancer (2018), 17(1):131.
  5. 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 21 expression and signaling in a rat tail caudal intervertebral disc degeneration model. Spine (2017) 42(8): E448-E458.
  6. 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-B pathway in intrahepatic cholestasis of pregnancy. J Mol Cell Biol. (2016) 8(6):530-541.
  7. Lu L, Lin CD, Yan ZJ, Wang S, Zhang YH, Wang SH, Wang JL, Liu C, Chen JF*. Kindlin-3 is essential for resting 41 integrin-mediated firm cell adhesion under shear flow conditions J Biol Chem. (2016) 291(19): 10363-71.
  8. 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 7 deficiency exacerbates DSS colitis by evoking aberrant innate immunity. Mucosal Immunol. (2015) 9(2): 391-400.
  9. 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.
  10. 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).
  11. Liu J, Fu T, Peng B, Sun H, Li GH*, Chen JF*. The hydrophobic contacts between the center of I domain and 1/7 helices hold integrin 47 in low-affinity state. FEBS J. (2014), 281: 2519-26.
  12. 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 47. J Cell Sci. (2013), 126:5030-41.
  13. Yue J, Pan YD, Sun LF, Zhang K, Liu J, Lu L, Chen JF*. The unique disulfide bond-stabilized W1 4-1 loop in 4-propeller domain regulates integrin 47 affinity and signaling. J Biol Chem. (2013), 288(20): 14228-37.
  14. 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 47. J Biol Chem. (2012), 287(19): 15749-59.
  15. 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)
  16. Zhang K, Chen JF*. The regulation of integrin function by divalent cations. Cell Adhes Migr. (2012), 6 (1): 1C10. (invited review)
  17. Sun H, Wu YM, Qi JP, Pan YG, 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 47. J Biol Chem. (2011), 286(14): 12086-92.
  18. Pan YD, Zhang K, Qi JP, Yue J, Springer TA*, ChenJF*. Cation-p interaction regulates ligand-binding affinity and signaling of integrin 47. Proc. Natl. Acad. Sci. U. S. A. (2010), 107: 21388-93.
  19. Chen JF, Yang W, Kim M, Carman CV, Springer TA. Regulation of Outside-In Signaling and Affinity by the I domain of Integrin L2. Proc. Natl. Acad. Sci. U. S. A. (2006), 103:13062-67.
  20. 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 47. J Biol Chem. (2004), 279: 55556-61.
  21. Chen JF, Salas A., and Springer T. A. Bistable regulation of integrin adhesiveness by a bipolar metal ion cluster. Nature Struct Biol. (2003), 10(12): 995-1101.
  22. 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. (# authors contribute equally to this paper)
  23. 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.
  24. 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.
  25. Chen JF, Li Y, Wang E, Wang Y. High-level expression and single-step purification of leucyl-tRNA synthetase from Escherichia coli. Protein Expres Purif. (1999), 15(1): 115-20.
  26. Chen JF, Li Y, Jiang WH, Yang YL, Zhao GP, Wang ED. Secretory Expression of GL-7-ACA Acylase in E. coli. Acta Biochimica et Biophysica Sinica. (1998), 30(4): 393-6.

Education Background & Academic Experience
2007- present: Principal Investigator, Professor, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China
2001-2007: Research Fellow, Harvard Medical School,The CBR Institute for Biomedical Research, Boston, MA U.S.A.
2000-2001: Visiting Scholar, Institut de biologie Moleculaire et Cellulaire du CNRS, 67084 Strasbourg, France
1996-2001: Ph.D. in Biochemistry and Molecular Biology, Shanghai Institute of Biochemistry, Chinese Academy of Sciences, shanghai, China.
1991-1996: B.S. in Microbiology, Fudan University, Shanghai, China.

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