College of Basic Medical Sciences

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WU Xuefeng

Email: xuefengwu@shsmu.edu.cn

Tel: 021-63846590-776684

Research Field

  • Inflammation plays a critical role in multiple steps in cancer. Our group focuses on the cellular and molecular mechanisms linking inflammation and cancer. Currently ongoing projects include: 1. Metabolic regulation of macrophage and dendritic cell; 2. Regulation of T/Treg cell antitumor immunity by cellular stress and homeostasis; 3. Regulation of immune responses by cross-talks between immune and tumor cells within Tumor Microenvironments and their function in cancer progression and metastasis. Our long-term goal is to develop drugs and new strategies for treating patients suffering from immunological diseases and cancers.

Personal Introduction

  • 1995-2002 Nankai University B.S. (1999)/M.S. (2002)

  • 2003-2008 The Pennsylvania State University Ph.D.

  • 2002-2003 Shanghai Rongsheng Biotech Ltd.       Tech Center

  • 2008-2009 M. D. Anderson Cancer Center         Postdoctoral Fellow

  • 2010-2014 University of California, San Diego     Postdoctoral Fellow/Assistant Project Scientist

  • 2014-2016 Ionis Pharmaceuticals              Senior Scientist

  • 2016.03-Present Shanghai Institute of Immunology     Principal Investigator

Scientific Research Projects

  • Precision diagnosis and treatment and application of severe infectious diseases in children,National Key Research and Development Project,2021YFC2701800, 2022-2024,Key Participant.

  • Mechanism of ubiquitin-conjugating enzyme Ubc13 regulating NLRP3 inflammasome, Shanghai Science Committee 21ZR1456200 2021-2024 PI.

  • Clinical study of mesenchymal stem cells in the treatment of psoriasis and psoriatic arthritis, National Key Research and Development Project,2020YFA0112900, 2020-2024,Key Participant;

  • Overseas high-level talents Youth Project,2017/9-2022/12 PI.

  • Function and regulation of ubiquitin conjugating enzyme Ubc13 in dendritic cells. General Program of National Natural Science Foundation of China (NSFC) 31670910,2017/1-2020/12, PI.

Publications

  • Hongrui Xiang, Yuexiao Tao, Zhenyan Jiang, Xian Huang, Huizi Wang, Wei Cao, Jia Li, Rui Ding, Mingyi Shen, Ru Feng, Linsen Li, Chenyang Guan, Jiamin Liu, Jun Ni, Lei Chen, Zhengting Wang, Youqiong Ye, Qing Zhong, Junling Liu,* Qiang Zou,* and Xuefeng Wu* Vps33B controls Treg cell suppressive function through inhibiting lysosomal nutrient sensing complex-mediated mTORC1 activation. Cell Reports (2022), https://doi.org/10.1016/j.celrep.2022.110943

  • Wang D#, Yuan T#, Liu J#, Wen Z, Shen Y, Tang J, Wang Z*, Wu X*. ATG16L2 inhibits NLRP3 inflammasome activation through promoting ATG5-12-16L1 complex assembly and autophagy. Eur J Immunol. 2022 Apr 15. PMID: 35426127

  • Kim MC#, Borcherding N#, Ahmed KK#, Voigt AP#, Vishwakarma A, Kolb R, Kluz PN, Pandey G, De U, Drashansky T, Helm EY, Zhang X, Gibson-Corley KN, Klesney-Tait J, Zhu Y, Lu J, Lu J, Huang X, Xiang H, Cheng J, Wang D, Wang Z, Tang J, Hu J, Wang Z, Liu H, Li M, Zhuang H, Avram D, Zhou D, Bacher R, Zheng SG, Wu X*, Zakharia Y*, Zhang W*. CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells. Nat Commun. 2021; 12(1):5764. PMID: 34599187

  • Ni J, Guan C, Liu H, Huang X, Yue J, Xiang H, Jiang Z, Tao Y, Cao W, Liu J, Wang Z, Wang Y*, Wu X*. Ubc13 promotes K63-linked poly-ubiquitination of NLRP3 to activate inflammasome. Journal of Immunology 2021; 206(10):2376-2385. PMID: 33893171

  • Guan C, Huang X, Yue J, Xiang H, Shaheen S, Jiang Z, Tao Y, Tu J, Liu Z, Yao Y, Yang W, Hou Z, Liu J, Yang XD, Zou Q, Su B, Liu Z, Ni J*, Cheng J*, Wu X*. SIRT3-mediated deacetylation of NLRC4 promotes inflammasome activation. Theranostics 2021; 11(8):3981-3995. PMID: 33664876

  • Zhu Q, Yu T, Gan S, Wang Y, Pei Y, Zhao Q, Pei S, Hao S, Yuan J, Xu J, Hou F, Wu X, Peng C, Wu P, Qin J, Xiao Y. TRIM24 facilitates antiviral immunity through mediating K63-linked TRAF3 ubiquitination. J Exp Med. 217(7):e20192083. (2020). PMID: 32324863

  • Yang XD, Li W, Zhang S, Wu D, Jiang X, Tan R, Niu X, Wang Q, Wu X, Liu Z, Chen LF, Qin J, Su B. PLK4 deubiquitination by Spata2-CYLD suppresses NEK7-mediated NLRP3 inflammasome activation at the centrosome. EMBO J. 39 (2):e102201. (2020) PMID: 31762063

  • Wang T, Cao Y, Zheng Q, Tu J, Zhou W, He J, Zhong J, Chen Y, Wang J, Cai R, Zuo Y, Wei B, Fan Q, Yang J, Wu Y, Yi J, Li D, Liu M, Wang C, Zhou A, Li Y, Wu X, Yang W, Chin YE, Chen G, Cheng J. SENP1-Sirt3 Signaling Controls Mitochondrial Protein Acetylation and Metabolism. Mol Cell. 22; 75(4):823-834 (2019). PMID: 31302001

  • Huang X, Zuo Y, Wang X, Wu X, Tan H, Fan Q, Dong B, Xue W, Chen GQ, Cheng J. SUMO-Specific Protease 1 Is Critical for Myeloid-Derived Suppressor Cell Development and Function. Cancer Res. 79(15):3891-3902. (2019). PMID: 31186231

  • Yu X, Lao Y, Teng XL, Li S, Zhou Y, Wang F, Guo X, Deng S, Chang Y, Wu X, Liu Z, Chen L, Lu LM, Cheng J, Li B, Su B, Jiang J, Li HB, Huang C, Yi J, Zou Q. SENP3 maintains the stability and function of regulatory T cells via BACH2 deSUMOylation. Nat Commun. 9(1):3157. (2018) PMID: 30089837

  • Todoric J#, Antonucci L#, Di Caro G#, Li N#, Wu X, Lytle NK, Dhar D, Banerjee S, Fagman JB, Browne CD, Umemura A, Valasek MA, Kessler H, Tarin D, Goggins M, Reya T, Diaz-Meco M, Moscat J, Karin M. Stress-Activated NRF2-MDM2 Cascade Controls Neoplastic Progression in Pancreas. Cancer Cell. 32(6):824-839.e8. (2017) PMID: 29153842

  • Kaneda MM, Messer KS, Ralainirina N, Li H, Leem C, Gorjestani S, Woo G, Nguyen AV, Figueiredo CC, Foubert P, Schmid MC, Pink M, Winkler DG, Rausch M, Palombella VJ, Kutok J, McGovern K, Frazer KA, Wu X, Karin M, Sasik R, Cohen EE, Varner JA. PI3Kγ is a molecular switch that controls immune suppression. Nature 2016 Sep 19. doi: 10.1038/nature19834. [Epub ahead of print] PMID: 27642729

  • Wu X, M Karin. Emerging roles of Lys63-linked polyubiquitylation in immune responses. Immunol Rev. 266(1):161-74. (2015) PMID: 26085214

  • Jo M, Schmidt J, Zhou T, Wu X, Crosby J, Brand E, Kim Y, and Macleod R. Strong pharmacological activity of locally administered next-generation antisense oligonucleotides (ASOs) in orthotopic lung cancer mouse models. Journal of Thoracic Oncology. 11(25): S26 (2015). DOI: http://dx.doi.org/10.1016/j.jtho.2015.12.043

  • Inokuchi-Shimizu S, EJ Park, YS Roh, L Yang, B Zhang, J Song, S Liang, M Pimienta, K Taniguchi, X Wu, K Asahina, W Lagakos, MR Mackey, S Akira, MH Ellisman, DD Sears, JM Olefsky, M Karin, DA Brenner, E Seki. TAK1-Mediated Autophagy and Fatty Acid Oxidation Prevent Hepatosteatosis and Tumorigenesis. J Clin Invest. 124(8):3566-78. (2014) PMID: 24983318

  • Charlaftis N, Suddason T, X Wu, M Karin and E Gallagher. The MEKK1 PHD ubiquitinates TAB1 to activate MAPKs in response to cytokines. EMBO J. 33(21):2581-96. (2014) PMID: 25260751

  • Zhang H, H Hu, N Greeley, J Jin, A Matthews, E Ohashi, M Caetano, H Li, X Wu, P Mandel, J McMurray, SJ Moghaddam, S-C Sun, S. Watowich. STAT3 restrains RANK- and TLR4-mediated signalling by suppressing expression of the E2 ubiquitin-conjugating enzyme Ubc13. Nature Communications 2014 Dec 15; 5:5798. doi: 10.1038/ncomms6798. (2014) PMID: 25503582

  • Wu X, W Zhang, J Font-Burgada, T Palmer, AS Hamil, SK Biswas, M Poidinger, N Borcherding, Q Xie, LG Ellies, N Lytle, LW Wu, J Yang, SF Dowdy, T Reya, M Karin. Ubiqutin-conjugating Enzyme Ubc13 Controls Breast Cancer Metastasis through a TAK1-p38 MAP Kinase Cascade. PNAS (2014) 111(38): 13870-5. PMID: 25189770 Highlighted in International, National and Regional Media including Union-Tribute San Diego Sept 7, 2014; and Science Signaling Editors’ Choice 7 (345), ec264.

  • Li N, Wu X, Holzer RG, Lee JH, Todoric J, Park EJ, Ogata H, Gukovskaya AS, Gukovsky I, Pizzo DP, Vandenberg S, Tarin D, Atay C, Arkan MC, Deerinck TJ, Moscat J, Diaz-Meco M, Dawson D, Erkan M, Kleeff J, Karin M. Loss of acinar cell IKKα triggers spontaneous pancreatitis in mice. J Clin Invest. 123(5):2231-43. (2013) PMID: 23563314

  • Zhang W, Tan W, Wu X, Poustovoitov M, Strasner A, Li W, Borcherding N, Ghassemian M, Karin M. A NIK-IKKα Module Expands ErbB2-Induced Tumor-Initiating Cells by Stimulating Nuclear Export of p27/Kip1. Cancer Cell. 23(5):647-59. (2013) PMID: 23602409

  • Mancino A, Habbeddine M, Johnson E, Luron L, Bebien M, Memet S, Fong C, Bajenoff M, Wu X, Karin M, Caamano J, Chi H, Seed M, Lawrence T. I kappa B kinase alpha (IKKα) activity is required for functional maturation of dendritic cells and acquired immunity to infection. EMBO J. 32(6):816-28. (2013) PMID: 23422957

  • Chang JH, Xiao Y, Hu H, Jin J, Yu J, Zhou X, Wu X, Johnson HM, Akira S, Pasparakis M, Cheng X, Sun SC. Ubc13 maintains the suppressive function of regulatory T cells and prevents their conversion into effector-like T cells. Nat Immunol. 13: 481-490 (2012) PMID: 22484734

  • Wu X#, Zhang M# and Sun S-C. Mutual regulation between deubiquitinase CYLD and Retroviral Oncoprotein Tax. Cell & Bioscience 2011 Aug 8; 1(1):27. PMID: 21824392

  • Hu H#, Wu X#, Jin W, Chang M, Cheng X and Sun S-C. Noncanonical NF-κB regulates inducible costimulator (ICOS) ligand expression and T follicular helper cell development. PNAS 2011 Aug 2; 108(31):12827-32. Epub 2011 Jul 18. [* co-first author] PMID: 21768353

  • Zhang M, Lee AJ, Wu X, Sun SC. Regulation of antiviral innate immunity by deubiquitinase CYLD. Cell Mol Immunol. 8(6):502-4 (2011). PMID: 21946435

  • Xu G, Y-C Lo, Q Li, G Napolitano, Wu X, X Jiang, Karin M and Wu H. Crystal structure of the inhibitor of κB kinase β (IKKβ). Nature 472 (7343):325-30 (2011).  PMID: 21423167

  • Lee A#, Wu X#, H Cheng, X Zhou, X Cheng, and S-C Sun. CARMA1 regulation of Treg development involves modulation of IL-2 receptor signaling. J. Biol Chem. 2010 Mar25. 285(21): 15696-703 (2010). PMID: 20233721

  • Wu X, M Yamamoto, S Akira, and S-C Sun. Regulation of hematopoiesis by the K63-specific   ubiquitin-conjugating enzyme Ubc13. PNAS 106 (49): 20836-41 (2009). PMID: 19926860

  • Zhang M#, Wu X#, AJ Lee, W Jin, M Chang, A Wright, T Imaizumi, and S-C Sun. Regulation of IKK-related kinases and antiviral responses by tumor suppressor CYLD. J Biol Chem. 283(27): 8621-6 (2008). PMID: 18467330

  • Wu X, S-C Sun. Retroviral oncoprotein Tax deregulates NF-κB by activating Tak1 and mediating Tak1-IKK physical association. EMBO Rep. 8(5): 510-5 (2007). PMID: 17363973

  • Reiley WW, Jin W, Lee AJ, Wright A, Wu X, Tewalt EF, Leonard TO, Norbury CC, Fitzpatrick L, Zhang M, Sun SC. Deubiquitinating enzyme CYLD negatively regulates the ubiquitin-dependent kinase Tak1 and prevents abnormal T cell responses. J Exp Med. 204(6): 1475-85 (2007). PMID: 17548520

  • Jin W, Reiley WR, Lee AJ, Wright A, Wu X, Zhang M, Sun SC. Deubiquitinating enzyme CYLD regulates the peripheral development and naive phenotype maintenance of B cells. J Biol Chem. 282(21): 15884-93 (2007). PMID: 17392286

  • Babu G, Waterfield M, Chang M, Wu X, Sun SC. Deregulated activation of oncoprotein kinase Tpl2/Cot in HTLV-I-transformed T cells. J Biol Chem. 281(20): 14041-7 (2006). PMID: 16565081

  • Babu GR, Jin W, Norman L, Waterfield M, Chang M, Wu X, Zhang M, Sun SC. Phosphorylation of NF-kappaB1/p105 by oncoprotein kinase Tpl2: implications for a novel mechanism of Tpl2 regulation. Biochim Biophys Acta. 1763(2): 174-81 (2006). PMID: 16448710

  • Reiley W, M Zhang, Wu X, E Granger, and S-C Sun. Regulation of the deubiquitinating enzyme CYLD by IKKγ-dependent phosphorylation. Mol. Cell. Biol. 25(10): 3886-95 (2005). PMID: 15870263

  • Abdul-Kareem AR, Sheng C, Shi, M, An C, Wu X, Li D and Du R. Isolation and Characterization of a Salt-induced Transcript from Halophyte Spartina Anglica Using DDRT-PCR. Acta Scientiarum Naturalium Universitatis Nankaiensis (Natural Science Edition) 36 (2) 8-14 (2003).

  • Ye M, Sheng C, Shi M, An C, Ji J, Wu X, Du R and Li D. Detection of Potato Spindle Tuber Viroid by Single-enzyme RT-PCR. Acta Agriculturae Boreali-Sinica 17 (1) 41-45 (2002).

  • Ji J, Sheng C, Shi M, An C, Wu X, Li D and Du R. A Study on the Transformation of Wheat with Salt-tolerant Gene HVA1 by Method Deflating Pollen Tube. Journal of Triticeae Crops 22(2): 10-13 (2002).