Home  /  Faculty  /  Principal Investigators
  • 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.
  • E-mail：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) Na？ve 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) Na？ve 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.
    Selected Publications
    1.  J Xiao*, S Wang*, LL Chen*, XY Ding, MS Han, YX Zheng, MC Wang, D Yang, N Li, C Dong, H Shen, SF Wu, M Hu, C Su, WY Li, LJ Hui, YQ Ye#, HR Tang#, B Wei#, HY Wang#. 25-Hydroxycholesterol regulates lysosome AMPK activation and metabolic reprogramming to educate immunosuppressive macrophages, Immunity. 2024 Accept
    2. X Zheng*, Q Jiang*, MS Han, FF Ye, MC Wang, Y Qiu, JL Wang, MX Gao, FJ Hou, and HY Wang#. FBXO38 regulates macrophage polarization to control the development of cancer and colitis, Cell Mol Immunol. 2023 Nov;20(11):1367-1378.
    3. F Zhang*, BK Zhang*, HH Ding , XY Li, XL Wang , XM Zhang , QJ Liu , QY  Feng , MS Han , LL Chen , LL Qi, D Yang , XJ  Li , XG Zhu, Q Zhao, JQ Qiu, ZJ Zhu, HR Tang, N Shen#, HY Wang#, B Wei#. The Oxysterol Receptor EBI2 Links Innate and Adaptive Immunity to Limit IFN Response and Systemic Lupus Erythematosus, Adv Sci (Weinh). 2023 Sep;10(27):e2207108.
    4. LL Qi*, XJ Li *, F Zhang * , XG  Zhu , Q Zhao, D Yang , SJ Hao , T Li , XY  Li , TK Tian , J Feng , XC Sun, XL Wang, SY Gao, HZ Wang , J Ye, SB Cao, YL He, HY Wang#, B Wei# . VEGFR-3 signaling restrains the neuron-macrophage crosstalk during neurotropic viral infection, Cell Reports. 2023 May 30;42(5):112489.
    5. D Yang, TK Tian, XJ Li, BK Zhang, LL Qi, F Zhang, MS Han, S Wang, J Xiao, YY Gou, RR Zhang, QJ Liu, S Su, JH Liu, XW Huang, Q Gao, LJ Hui, HR Tang, HY Wang#, B Wei#. ZNT1 and Zn2+ control TLR4 and PD-L1 endocytosis in macrophage to improve chemotherapy efficacy against liver tumor, Hepatology. 2023 Oct 9. Online ahead of print.
    6. X Zheng, J Xiao, Q Jiang, LM Zheng, C Liu, C Dong, YX Zheng, PL Ni, C Zhang, F Zhang, RY Zhong, HH Ding, Q Wang, Y Qiu, MX Gao, JP Ding, N Shen, B Wei#, HY Wang#. AKT2 reduces IFNβ1 production to modulate antiviral responses and systemic lupus erythematosus. EMBO J. 2022 Mar 15;41(6): e108016.
    7. L Ma*, WY Li*, YB Zhang*, LL Qi*, Q Zhao, N Li, Y Lu, LQ Zhang, F Zhou, YC Wu, YN He, HX Yu, YL He#, B Wei#, HY Wang#. FLT4/VEGFR3 activates AMPK to coordinate glycometabolic reprogramming with autophagy and inflammasome activation for bacterial elimination. Autophagy. 2022 Jun;18(6):1385-1400.
    8. XJ Li*, LL Qi*, D Yang, SJ Hao, F Zhang, XG Zhu, Y Sun, C Chen, J Ye, J Yang, L Zhao, D M Altmann, SB Cao, HY Wang#, B Wei#. Meningeal lymphatic vessels mediate neurotropic viral drainage from the central nervous system. Nat Neurosci. 2022 May;25(5):577-587.
    9. C Zhang*, WY Li *, XB Lei, ZF Xie, LL Qi, H Wang, X Xiao, J Xiao, YX Zheng, C Dong, X Zheng, SY Chen, JF Chen, B Sun, J Qin, QW Zhai, JS Li, B Wei#, JW Wang#, HY Wang#. Targeting lysophospholipid acid receptor 1 and ROCK kinases promotes antiviral innate immunity. Sci Adv. 2021 Sep 17;7(38): eabb5933.
    10. F Zhang*, LL Qi*, QY Feng, BK Zhang, XY Li, C Liu, WY Li, QJ Liu, D Yang, Y Yin, C Peng, H Wu, ZH Tang, X Zhou, Z Xiang, ZJ Zhang, HY Wang#, B Wei#. HIPK2 phosphorylates HDAC3 for NF-κB acetylation to ameliorate colitis-associated colorectal carcinoma and sepsis. PNAS. 2021 Jul 13;118(28): e2021798118.
    11. ZQ Li*, J Xiao*, XY Xu*, WY Li*, RY Zhong, LL Qi, JH Chen, GZ Cui, S Wang, YX Zheng, Y Qiu, S Li, X Zhou, Y Lu, JY Lyu, B Zhou, JW Zhou, NH Jing, B Wei#, J Hu#, HY Wang#. M-CSF, IL-6 and TGF-β promotes generation of a new subset of tissue repair macrophages for traumatic brain injury recovery. Sci Adv. 2021 Mar 12;7(11): eabb6260.
    12. J Xiao*, WY Li *, X Zheng, LL Qi, H Wang, C Zhang, XP Wan, YX Zheng, RY Zhong, X Zhou, Y Lu, ZQ Li, Y Qiu, C Liu, F Zhang, YB Zhang, XY Xu, ZZ Yang, HL  Chen, QW Zhai, B Wei#, Hongyan Wang #. Targeting 7-Dehydrocholesterol Reductase Integrates Cholesterol Metabolism and IRF3 Activation to Eliminate Infection. Immunity. 2020 Jan 14;52(1):109-122.e6.
    13. C Liu, XY Xu, L Han, XP Wan, LM Zheng, CY Li, J Xiao, RY Zhong, X Zheng, Q Wang, HL Chen, B Wei#, H Wang#. LRCH1 deficiency enhances LAT signalosome formation and CD8+ T cell responses against tumor and pathogens. PNAS 2020;117(32):19388-19398
    14. Q Wang*, X Zhou*, L Yang*, YJ Zhao, ZH Chew, J Xiao, C Liu, X Zheng, YX Zheng, Q Shi,, QQ Liang#, YJ Wang #*, H Wang#. The natural compound Notopterol binds and targets JAK2/3 to ameliorate inflammation and arthritis. Cell Reports 2020;32:108158
    15. Y Lu*, Y Qiu*, P Chen, H Chang, L Guo, F Zhang, L Ma, C Zhang, X Zheng, J Xiao, R Zhong, L Han, X Xu, Y Zhang, D Li, G Zhong, R Boyton, Y Huang, Y He, R Hu#, B Wei#, H Wang# The ER-localised Hrd1 ubiquitinates and inactivates Usp15 to promote TLR4-induced inflammation during bacterial infection. Nature Microbiology, 2019,4:2331-46
    16. X Zhou, WY Li S Wang, P Zhang, Q Wang, J Xiao, C Zhang, X Zheng, X Xu, S Xue, L Hui, H Ji, B Wei#, H Wang#. YAP aggravates inflammatory bowel disease (IBD) via regulating M1/M2 macrophage polarization and gut microbial homeostasis. Cell Reports, 2019, 27;1176-89
    17. T Zhou#, MC Luo*, W Cai, SY Zhou, DY Feng, CD Xu, H. Wang#. Runt-related transcription factor 1 (RUNX1) promotes TGF-β-induced renal tubular epithelial-to-mesenchymal transition (EMT) and renal fibrosis through the PI3K subunit p110δ. EBioMedicine, 2018.31:217-225
    18. Q Wang*, X Zhou*, YJ Zhao, J Xiao, Y Lu, Q Shi, YJ Wang#, H. Wang#, QQ Liang#. Polyphyllin I Ameliorates Collagen-Induced Arthritis by Suppressing the Inflammation Response in Macrophages Through the NF-kB Pathway. Frontiers in Immunology, 2018.9: article 2091.
    19. XY Xu*, L Han*, G. Zhao, SJ Xue, Y Gao, J Xiao, ZY Wu, JP Ding, B Wei, RG Hu, H Wang. LRCH1 interferes with DOCK8-Cdc42 module-induced T cell migration and ameliorates multiple sclerosis. J Exp Med, 2017; 214(1):209-226.
    20. 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;16:1-10
    21. Luo MC*, Zhou SY*, Feng DY, Xiao J, Li WY, Xu CD, Wang HY#, Zhou T#. Runt-related Transcription Factor 1 (RUNX1) Binds to p50 in Macrophages and Enhances TLR4-triggered Inflammation and Septic Shock. J Biol Chem. 2016;291 (42), 22011-22020.
    22. WY Li*, J Xiao*, X Zhou, M Xu, C Hu, X Xu, Y Lu, CLiu, S Xue, LNie, H Zhang, ZLi, Y Zhang, F Ji, L Hui, W Tao, B Wei# and H Wang#, STK4 regulates TLR pathways and protects against chronic inflammation–related hepatocellular carcinoma. J Clin Invest, 2015; 125(11):4239-54
    23. Li C*, Jiao S*, Wang G, Gao Y, He X, Liu C, Zhang G, Wei B, Chen H#, Wang H#. The immune adaptor ADAP regulates reciprocal TGF-b1-integrin crosstalk to protect from H5N1 influenza virus infection. PLoS Pathogens, 2015, 11(4):e1004824
    24. 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, 25:655-73 (Cover Story)
    25. 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-kB signaling and protects from endotoxin shock. Immunity, 2014, 40: 501-514 (Cover Story)
    26. 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;
    27. 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
    28. Zhang Y and Wang H#. Integrin signaling and function in immune cells. Immunology, 2012;4(135):267-75
    29. Wang H#, Lim D and Rudd CE. Integrin signaling and immunopathology Semin Immunopathol 2010;32(2):173-82
    30. 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.
    31. 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.
    32. 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
    33. 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
    34. 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.
    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
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