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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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WANG Hongyan
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: hongyanwang@@sibcb.ac.cn

Research Areas
Immune cells, Inflammation and Immune-mediated Inflammatory Diseases

Research Interests

Immune-mediated Inflammatory Diseases (IMIDs) are a group of diseases involving inappropriate or excessive immune responses caused or accompanied by cytokine dysregulation and acute or chronic inflammation. This includes a wide variety of illness, such as autoimmune diseases, infection, and inflammation-related cancer. T lymphocytes and macrophages are major immune cells which mediate inflammatory responses and play important role against infection, tumor and autoimmune diseases. (1) Naïve T lymphocytes use surface T-Cell-Receptor (TCR) or chemokine receptor to generate the ¡°inside-out¡± signaling pathway to enhance integrin activity and cell adhesion. This enables T cell migration at the right time to the right places. At the local inflammation sites, T cells differentiate into different T-cell subsets including Tregs, Th1, Th17 or CD8+ CTLs et al, which mediate immune responses against infection or the development of autoimmune diseases. (2) Macrophages use Toll-like receptors and other receptors to sense invading pathogens and activate various transcription factors such as NF-kB or IRFs. This leads to secretion of pro-inflammatory cytokines (IL-6, IL-1, TNF-alpha), anti-inflammatory cytokine (IL-10) or anti-viral cytokines (IFNs), which are essential to control infection or for the development of inflammation-related cancers.
We are interested in the following research projects.
(1) Naïve T lymphocytes generate the ¡°inside-out¡± signaling pathway to enhance integrin activity and cell adhesion. Integrins also send ¡°outside-in¡± signaling for cell-ECM or cell-cell adhesion, and cell proliferation, differentiation, or homing. We would like to identify new signaling proteins regulating ¡°inside-out¡± and ¡°outside-in¡± signaling pathways in T cells.
(2) Identify new signaling molecules in macrophages that mediate inflammation responses and phagocytosis during bacterial infection.
(3) The physiological and pathological relevance of immune-cell mediated inflammation in autoimmune disease, infection, cancer or tissue repair.
Left image£ºImmunity, 2014, Cover Story; Middle image: Cell Research, 2015, Cover Story; Right image: PLos Pathogens, 2015

Selected Publications

  1. SJ Xue, C Liu, XJ Sun, WY Li, C Zhang, X Zhou, Y Lu, J Xiao, CY Li, XY Xu, B Sun, GL Xu, H Wang#. TET3 inhibits IFN-I production independent of DNA demethylation. Cell Reports, 2016; Accepted
  2. W Li, J Xiao, X Zhou, M Xu, C Hu, X Xu, Y Lu, C Liu, S Xue, L Nie, H Zhang, Z Li, Y Zhang, F Ji, L Hui, W Tao, B Wei# and H Wang#. STK4 regulates TLR pathways and protects against chronic inflammation¨Crelated hepatocellular carcinoma. The Journal of Clinical Investigation, 2015; 125(11):4239-54
  3. Li C, Li W, Xiao J, Jiao S, Sheng C, Rudd CE, Wei B, Wang H#. ADAP and SKAP55 deficiency suppresses PD-1 expression in CD8+ cytotoxic T lymphocytes for enhanced anti-tumor immunotherapy. EMBO Mol Med, 2015: e201404578
  4. Jiao S, Li C, Wang G, Gao Y, He X, Liu C, Zhang G, Wei B, Chen H, Wang H#. The immune adaptor ADAP regulates reciprocal TGF-¦Â1-integrin crosstalk to protect from H5N1 influenza virus infection. PLoS Pathogens, 2015, 11(4):e1004824
  5. Fu X, Xiao J, Wei Y, Guo H, Li S, Liu Y, Yin J, Li D, Wang H#, Hu P#. Combination of four pro-inflammatory cytokines promotes long term muscle stem cell expansion in vitro. Cell Research, 2015, May 15. doi: 10.1038/cr.2015.58 (Cover Story)
  6. Zhang Y, Lu Y, Ma L, Jiao S, Chen J, Gao Y, Liu C, Duan Z, Li D, He Y, Wei B#, Wang H# Activation of vascular endothelial growth factor receptor-3 in macrophages restrains TLR-NF-¦ÊB signaling and protects from endotoxin shock Immunity, 2014, 40: 501-514 (Cover Story)
  7. Huang Y, Jiao S, Tao X, Tang Q#, Jiao W, Xiao J, Xu X, Zhang Y, Liang G, Wang H # Met-CCL5 represents an immunotherapy strategy to ameliorate rabies virus infection. J Neuroinflammation 2014,11:146;
  8. Zhang M, Zhou H, Zheng C, Xiao J, Zuo E, Liu W, Xie D, Shi Y, Wu C, Wang H, Li D, Li J. The Roles of Testicular C-kit Positive Cells in De novo Morphogenesis of Testis. Sci Rep 2014; 4: 5936; 1-11
  9. Yu T, Tao Y, Yang1 M, Chen P, Gao X, Zhang Y, Zhang T, Chen Z, Hou J, Zhang Y, Ruan K, Wang H, Hu R. Profiling human protein degradome delineates cellular responses to proteasomal inhibition and reveals a feedback mechanism in regulating proteasome homeostasis. Cell Res. 2014:1-17
  10. Wei B*, Han L*, Abbink T, Elisabetta G, Lim D, Thaker YR, Gao W, Zhai R, Wang J, Lever A, Jolly C, Wang H# and Rudd CE#. Immune adaptor ADAP in T cells regulates HIV-1 transcription and cell-cell viral spread via different co-receptors. Retrovirology, 2013:10:101
  11. Zhang Y and Wang H#. Integrin signaling and function in immune cells. Immunology, 2012;4(135):267-75
  12. Li C, Xu X, Wang H# and Wei B#. PD-1 and CTLA-4 mediated inhibitory signaling for T cell exhaustion during chronic viral infections. Journal of Clinical & Cellular Immunology, 2012, S7-10.
  13. Yao Y, Wang Y, Chen F, Huang Y, Zhu S, Leng Q, Wang H, Shi Y, Qian Y. NLRC5 regulates MHC class I antigen presentation in host defense against intracellular pathogens. Cell Res. 2012;22(5):836-47.
  14. Wang H#, Lim D and Rudd CE. Integrin signaling and immunopathology Semin Immunopathol 2010;32(2):173-82
  15. Raab M, Wang H, Lu Y, Smith X, Wu Z, Strebhardt K, Ladbury JE, Rudd CE. T cell receptor "inside-out" pathway via signaling module SKAP1-RapL regulates T cell motility and interactions in lymph nodes. Immunity 2010;32(4):541-56.
  16. Wang H, Lv Y and Rudd CE. SKAP1 is dispensable for chemokine induced T-cell migration. Immunol Letters 2010:128(2):148-53.
  17. Wang H, Wei B, Bismuth G, Rudd CE. SLP-76-ADAP adaptor module regulates LFA-1 mediated costimulation and T cell motility. PNAS 2009; 106(30):12436-41.
  18. Wang H and Rudd CE. SKAP-55, SKAP-55Related and ADAP adaptors modulate integrin-mediated immune cell adhesion. Trends Cell Biol 2008; 18(10):486-93.
  19. Schenider H*, Wang H*, Raab M, Valk E, Smith X, Lovatt M, Wu, Z, Strebhardt K, Rudd CE. Adaptor SKAP-55 binds p21 activating exchange factor RasGRP1 and negatively regulates the p21-ERK pathway in T-Cells. PLoS ONE. 2008;5;3(3):e1718
  20. Wang H, Liu H, Lu Y, Lovatt M, Wei B, Rudd CE. Functional defects of SKAP-55 deficient T-cells identify a regulatory role for the adaptor in LFA-1 adhesion. Mol Cell Biol. 2007;27(19):6863-75
  21. Wei B, da Rocha Dias S, Wang H, Rudd CE. CTL-associated antigen-4 ligation induces rapid T cell polarization that depends on phosphatidylinositol 3-kinase, Vav-1, Cdc42, and myosin light chain kinase. J Immunol. 2007;179(1):400-8.
  22. Jo E-K, Wang H, and Rudd CE. An essential role for SKAP-55 in LFA-1 clustering on T cells that cannot be substituted by SKAP-55R. J. Exp. Med. 2005;201(11):1733-9.
  23. Wang H, McCane F, Gordan J, Wu X, Raab M, Malik T, Davis D, Rudd CE. ADAP-SLP-76 binding differently regulates the supramolecular activation complex (SMAC) formation vs. conjugate formation. J. Exp. Med. 2004;200:1063-1074
  24. Wang H*, Moon EY*, Azouz A, Wu X, Smith A, Schneider H, Hogg N, Rudd CE. SKAP-55 regulates integrin adhesion and formation of T cell-APC conjugates. Nat Immunol. 2003;4(4):366-74.
  25. Rudd CE, Wang H. Hematopoietic adaptors in T-cell signaling: potential applications to transplantation. Am J Transplant. 2003;3(10):1204-10.
  26. Wilkinson B, Wang H, Rudd CE. Positive and negative adaptors in T cell signaling. Immunology 2004;111(4): 368-374.

Education Background & Academic Experience
1993-1998: BSc, Dept of Clinical Medicine, Anhui Medical University
1998-2001: MSc, Dept of Immunology, Anhui Medical University and Chinese Center of Disease Control (previously named "National Academy of Preventive Medicine"), Beijing
2001-2006: Research Associate, Dept of Immunology, Imperial College London, UK
2003-2006: Ph. D., Dept of Immunology, Imperial College London, UK
2006-2010: Research Fellow, Dept of Pathology, University of Cambridge, UK
Member of the Editorial Board
Cell Biochemistry and Function
Chinese Journal of Cell Biology

Research Team

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