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  • CHEN Zhengjun

  • Professor Dr. med.
    Center for Excellent in Molecular Cell Sciences, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China.

  • E-mail：zjchen@@sibcb.ac.cn
    Research Areas

  • Phosphorylated Protein Signaling and Cell Polarity Signaling in cell fate, cell behavior and tumorigenesis (liver carcinogenesis)

    Research Interests
  • Phosphoprotein Signaling Networks: we are particularly interested in studying how receptor tyrosine kinases like EGFR, FGFRs, VEGFR and IR interpret extracellular cues and integrate these signals into intracellular signaling modules and scaffolds that regulate the cellular dynamic processes: the significances of the signaling pathways of the growth factor receptors and the down stream protein complexes (SIRPs, SHP1/2, Csk-CBP, SKFs). Mechanistic studies determine how they transmit signals that control the dynamic assemble of phosphorylated protein complexes to regulate the cell fate, cell structure and behaviors. The long-term goal of the project is to identify novel pharmaceutical targets for diagnostic and treatment of cancer and diabetes.
     
    Cell Polarity is a universal biological process that is fundamental to all aspects of cell division, growth, development, and tissue morphogenesis. Polarity underlies the generation of diverse cell types by asymmetrically dividing stem cells, and provides the organizational structures for tissue architecture. Loss of cell polarity is one of the hallmarks of malignant tumors. Polarity has been implicated in a correlation with cell fate, cell behavior and tumorigenesis. Thus, the newly emerged interest is to understand how cell polarity protein complexes, such as Par-complex (Par3/Pa6/aPKC/ Cdc42/Lgl1) and Occludin-ZO (Zonula occluden) -2 complex, convert their polarity functions into various cellular processes in epithelial cells and in non-tight junction cells like immune cells . The objective is to uncover novel molecular mechanisms that regulate cellular intrinsic linkage between the cell polarity signaling and cell migration, proliferation, and tumorigenesis as well.
    Selected Publications
    1. Zhang Z.#, Li W.#, Yang G., Lu X, Qi X., Wang S., CaoC., Zhang P., Ren J., Zhao J., Zhang J., Hong S., Tan Y., Burchfield J., Yu Y., Xu T., Yao X., James D., Feng W.* and Chen Z* CASK modulates the assembly and function of Mint1/Munc18-1 complex to regulate insulin secretion. Cell Discov. Accepted.
    2. Wei Z, Lei J, Shen F, Dai Y, SunY, Liu Y, Dai Y, Jian Z, Wang S, Chen Z*, Liao K*, Hong S*. Cavin1 Deficiency Causes Disorder of Hepatic Glycogen Metabolism and Neonatal Death by Impacting Fenestrations in Liver Sinusoidal Endothelial Cells. Advanced Science, 202000963 2020, (https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202000963)
    3. Li JT,Yin M,Wang D,Wang J, Lei MZ, Zhang Y, Liu Y, Zhang L, Zou SW, Hu LP, Zhang ZG,Wang YP,Wen WY, Lu HJ, Chen ZJ, Su D, Lei QY*. BCAT2-mediated BCAA catabolism is critical for development of pancreatic ductal adenocarcinoma Nat Cell Biol. 2020 Feb;22(2): 167-174.
    4. Zhang, L., Lu, Y., Wang, Y., Wang, F., Zhai, S., Chen, Z., Cai, Z. (2020) PHF14 is required for germinal center B cell development. Cell Immunol. 358:104221. doi: 10.1016/j.cellimm.2020.104221. Epub 2020 Sep 28
    5. Zhang Q, Pan Y, Zeng B, Zheng X, Wang H, Shen X, Li H, Jiang Q, Zhao J, Meng Z, Li P, Chen Z, Wei H, Liu Z*. Intestinal lysozyme liberates Nod1 ligands from microbes to direct insulin trafficking in pancreatic beta cells. Cell Res. 2019 Jul;29(7):516-532
    6. Zhang L,Wei N,Cui Y,Hong Z, Liu X,Wang Q,Li S,Liu H,Yu H,Cai Y,Wang Q, Zhu J, Meng W, Chen Z*, Wang C*. The deubiquitinase CYLD is a specific checkpoint of the STING antiviral signaling pathway. PLoS Pathog. 2018 Nov 2;14(11):
    7. He B, Yang X, Li Y, Huang D, Xu X, Yang W, Dai Y, Zhang H, Chen Z*, Cheng W*. TLR9 (Toll-Like Receptor 9) Agonist Suppresses Angiogenesis by Differentially Regulating VEGFA (Vascular Endothelial Growth Factor A) and sFLT1 (Soluble Vascular Endothelial Growth Factor Receptor 1) in Preeclampsia. Hypertension. 2018 Apr;71(4):671-680.
    8. Zhang L, Huang Q, Lou J, Zou L, Wang Y, Zhang P, Yang G, Zhang J, Yu L, Yan D, Zhang C, Qiao J, Wang S, Wang S, Xu Y, Ji H, Chen Z*, Zhang Z*. A novel PHD-finger protein 14/KIF4A complex overexpressed in lung cancer is involved in cell mitosis regulation and tumorigenesis. Oncotarget. 2017 Mar 21;8(12):19684-19698.
    9. Yang B, Chen S, Wu M, Zhang L, Ruan M, Chen X, Chen Z* Mei C*, Mao Z*. PHF14: an innate inhibitor against the progression of renal fibrosis following folic acid-induced kidney injury. Sci Rep. 2017 Jan 3;7:39888. doi: 10.1038/srep39888.
    10. Zheng, C., Wang, Y., Yang, L., Zhou, S., Gao, Y., Li, F., Feng, Y., Wang, Z., Zhan, L., Yan, Q., Zhu, X., Wong, K. K., Chen, Z. *, Ji, H*. (2017)  Cell Division Cycle 42 plays a Cell type-Specific role in Lung Tumorigenesis Sci Rep. 4;7(1):10407. doi: 10.1038/s41598-017- 10891-0
    11. Zhang P, Wang S, Qiao J , Zhang L , Zhang Z , Chen Z* (2016)  Dual function of partitioning-defective 3 in the regulation of YAP phosphorylation and activation. Cell Discov.2:16021. doi: 10.1038/celldisc.
    12. Huang Q, Zhang L, Wang Y, Zhang C, Zhou S, Yang G, Li Z, Gao X, Chen Z*, and Zhang Z* (2013). Depletion of PHF14, coding for a novel histone-binding protein, caused neonatal lethality in mice due to respiratory failure. Acta Biochimica et Biophysica Sinica. 45(8):622-33,.
    13. Xie, C., Li, N., Chen, Z. J.*, Li, B. L., Song, B. L*.( 2011 ) The small GTPase Cdc42 interacts with Niemann-Pick C1-like 1 (NPC1L1) and controls its movement from endocytic recycling compartment to plasma membrane in a cholesterol-dependent manner. J Biol Chem.286(41):35933-42. doi: 10.1074/jbc.M111.270199.
    14. Zhang, K., Zhao, H., Ji, Z., Zhang, C., Zhou, P., Wang, L., Chen, Q., Wang, J., Zhang, P., Chen, Z., Zhu, H. H., Gao, W. Q (2011)  Shp2 promotes metastasis of prostate cancer by attenuating the PAR3/PAR6/aPKC polarity protein complex and enhancing epithelial-to-mesenchymal transition Oncogene. 35(10):1271-82.
    15. Du D, Xu F, Yu L, Zhang C, Lu X, Yuan H, Huang Q, Zhang F, Bao H, Jia L, Wu X, Zhu X, Zhang X, Zhang Z, Chen Z* (2010).. The tight junction protein, Occludin, regulates the directional migration of epithelial cells. Developmental Cell. 18(1):52-63,
    16. Yuan H, Zhang H, Wu X, Zhang Z, Du D, Zhou S, Brakebusch C, and Chen Z*. (2009) Hepatocyte-specific deletion of Cdc42 results in delayed liver regeneration after partial hepatectomy in mice. Hepatology 49:240-9.
    17. Lu X, Feng X, Man X, Yang G, Tang L, Du D, Zhang F, Yuan H, Huang Q, Zhang Z, Liu Y, Strand D, and Chen Z*. (2009)  Aberrant splicing of Hugl-1, the human homologue of Drosophila tumor suppressor gene lgl, is associated with hepatocellular carcinoma progression. Clin Cancer Res. 15 (10):3287-96.
    18. Feng X, Lu X, Man X, Zhou W, Jiang LQ, Knyazev P, Lei L, Huang Q, Ullrich A, Zhang Z*, and Chen Z*(2009). Overexpression of Csk binding protein (Cbp) contributes to renal cell carcinogenesis. Oncogene 28 (37):3320-31,
    19. Yang G, Li Q, Ren S, Lu X, Fang L, Zhou W, Zhang F, Xu F, Zhang Z, Zeng R, Lottspeich F, and Chen Z* (2009). Proteomic, functional and motif-based analysis of C-terminal Src kinase-interacting proteins. Proteomics.9(21):4944-61,.
    20. Zhou W, Feng X, Wu Y, Benge J, Zhang Z, and Chen Z* (2009)  FGF-receptor substrate 2 functions as a molecular sensor integrating external regulatory signals into the FGF pathway. Cell Research. 19(10): 1165-77
    21. Du, D., Pedersen, E., Wang, Z., Karlsson, R., Chen, Z., Wu, X., Brakebusch, C. (2009)  Cdc42 is crucial for the maturation of primordial cell junctions in keratinocytes independent of Rac1 Exp Cell Res. 315(8):1480-9. doi: 10.1016/j.yexcr.2008.11.012. Epub 2008 Dec 3.
    22. Ren, S., Yang, G., He, Y., Wang, Y., Li, Y., Chen, Z*. (2008) The conservation pattern of short linear motifs is highly correlated with the function of interacting protein domains BMC Genomics. 9:452. doi: 10.1186/1471-2164-9-452.
    23. Wang YG, Du D, Fang LH, Yang G, Zhang CY, Lottspeich F, Ullrich A and Chen ZJ*. (2006) Tyrosine Phosphorylated Par3 Regulates Epithelial Tight Junction Assembly Promoted by EGFR Signaling. EMBO J., 5: 5058-5070.
    24. Fang LH, Wang YG, Du D, Yang G, Kwok T, Kong S, Chen B, Chen D and Chen ZJ*. (2007). Cell polarity protein Par3 complexes with DNA-PK via Ku70 and regulates DNA double-strand break repair. Cell Res. 17: 100-116.(Highlighted by Cell and Nature Cell Biology)
    25. Wang YG, Li RX, Du D, Zhang CY, Yuan HX, Zeng R* and Chen ZJ*. (2006) Proteomic Analysis Reveals Novel Molecules Involved in Insulin Signaling Pathway. J Proteome. Res., 5: 846-855. (Featured Article in J Proteome. Res；Highlighted by J Proteome. Res 2006)
    26. Jiang QF, Feng XJ, Zhou WC, Knyazev P, Ullrich A and Chen Z*. (2006) Csk-binding protein (Cbp) negatively regulates epidermal growth factor-induced cell transformation by controlling Src activation. Oncogene, 25: 5495-5506.
    27. Yuan HX, Zhang L, Liu AH, Zhou H, Wang YG, Zhang H, Wang GQ, Zeng R, Zhang YL* and Chen ZJ*. (2006) Proteomic profiling of regionalized proteins in rat epididymis indicates consistency between specialized distribution and protein functions. J. Proteome.Res, 5:299-307.
    28. Zong XG, Eckert C, Yuan HX, Wahl-Schott C, Abicht H, Fang LH, Li RX, Mistrik P, Gerstner A, Much B, Baumann L, Michalakis S, Zeng R, Chen ZJ *and Biel M*. (2005) Novel Mechanism of Modulation of Hyperpolarization-activated Cyclic Nucleotide-gated Channels by Src Kinase. J. Biol. Chem., 280(40): 34224–34232.
    29. Wu Y, Chen ZJ, Ullrich A*. (2003) EGFR and FGFR signaling through FRS2 is subject to negative feedback control by ERK1/2. Biol.Chem.,384(8):1215-26.
    30. Wang, B., Xiao, Y., Ding, B. B., Zhang, N., Yuan, Xb, Gui, L., Qian, K. X., Duan, S., Chen, Z., Rao, Y., Geng, J. G*. (2003) Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity. Cancer Cell 4(1):19-29. doi: 10.1016/s1535-6108(03)00164-8.
    31. Wu, C. J., Chen, Z., Ullrich, A., Greene, M. I., O'Rourke, D. M. (2000) Inhibition of EGFR-mediated phosphoinositide-3-OH kinase (PI3-K) signaling and glioblastoma phenotype by signal-regulatory proteins (SIRPs) Oncogene 19(35):3999-4010. doi: 10.1038/sj.onc.1203748 .
    32. Seiffert, M., Cant, C., Chen, Z., Rappold, I., Brugger, W., Kanz, L., Brown, E. J., Ullrich, A., Buhring, H. J. (1999)  Human signal-regulatory protein is expressed on normal, but not on subsets of leukemic myeloid cells and mediates cellular adhesion involving its counterreceptor CD47. Blood 1;94(11):3633-43.
    33. Kharitonenkov A#, Chen ZJ#, Sures I, Wang H and Ullrich A. (1997)  A Family of Proteins that Inhibit Signaling through Tyrosine Kinase Receptors. Nature, 386: 181-186. (# co-first authors)
    Education Background & Academic Experience
  • 2000 – Present: Principal Investigator, Professor, Shanghai Institute of Biochemistry and Cell Biology, Center of Excellence in Molecular Cell Scinece, Chinese Academy of Sciences, Shanghai
    2012 – Present: Distinguished Adjunct Professor, School of Life Science and Technology,  ShanghaiTech Universtiy 
    1998 – 2000: Staff Scientist, Project Leader, Department of Molecular Biology, the Max-Planck-Institute of Biochemistry, Munich, Germany
    1993 – 1998: Post-doctoral Fellow, The Max-Planck-Institute of Biochemistry, Munich, Germany. Supervisor: Professor Dr. Axel Ulrich
    1989 – 1993 Doctor of Medicine (DR. MED.), the Faculty of Theoretical Medicine, Institute of Pharmacology and Toxicology, University Ulm, Ulm , Germany. 
    1989 – 1989 Visiting Scholar Fellow, Heinrich-Peter-Institute of Experimental Virology and Immunology, Hamburg University, Germany. 
    1983 – 1989 Research Assistant, Department of Biochemistry, the Second Military Medical University, Shanghai , China
    1978 – 1983 Bachelor of Medicine (Bsci.), Faculty of Military Medicine, the Second Military Medical University, Shanghai , China 
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