Research Areas:

Cell death plays an essential role for the survival of multicellular organisms. Too much or too little cell death can lead to many diseases. The best-known forms of regulated cell death is apoptosis. Necroptosis is a newly defined form of non-apoptotic cell death mediated by the receptor interacting protein kinase 3(RIPK3) and its substrate, mixed lineage kinase domain-like(MLKL). During necroptosis, cells can release damage-associated molecular patterns that crucially contribute to the pathogenesis of acute and chronic inflammatory diseases. Furthermore, recent findings indicates an additional role for the RIPK1/RIPK3/MLKL in the regulation of inflammatory responses. Our research mainly focus on the regulatory mechanisms of necroptosis and its role in inflammation and related-metabolic diseases.

Brief Biography:

2017 - present Professor, Principal Investigator, Shanghai Institute of Nutrition and Health (SINH), CAS

2013 - 2016 Professor, Professor, Principal Investigator, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

2012 - 2013 Postdoctoral Fellow, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

2006 - 2012 Postdoctoral Fellow, Department of Microbiology and Immunology, Kimmel Cancer Centre, Thomas Jefferson University, Philadelphia, PA, USA

Education:

2000-2006 Ph.D. Shanghai Institutes for Biological Sciences, the Chinese Academy of Sciences, Shanghai, China

1993-1997 B.S. Shandong University, China

Selected Publications: (*Corresponding Author)

1. Wu X, Zhao X, Li F, Wang Y, Ou Y, Zhang H, Li X, Wu X, Wang L, Li M, Zhang Y, Liu J, Xing M, Liu H, Tan Y, Wang Y, Xie Y, Zhang H, Luo Y, Li H, Wang J, Sun L, Li Y, Zhang H*. MLKL-mediated endothelial necroptosis drives vascular damage and mortality in systemic inflammatory response syndrome. Cell Mol Immunol 2024 Nov;21(11):1309-1321.
2. Deng X^#, Wang L^#, Zhai Y^#, Liu Q, Du F, Zhang Y, Zhao W, Wu T, Tao Y, Deng J, Cao Y, Hao P, Ren J, Shen Y, Yu Z, Zheng Y*, Zhang H*, Wang H*. RIPK1 plays a crucial role in maintaining regulatory T-Cell homeostasis by inhibiting both RIPK3- and FADD-mediated cell death. Cell Mol Immunol 2024 Jan;21(1):80-90.
3. Wu X, Wang Y, Chen B, Liu Y, Li F, Ou Y, Zhang H, Wu X, Li X, Wang L, Rong W, Liu J, Xing M, Zhao X, Liu H, Ge L, Lv A, Wang L, Wang Z*, Li M*, Zhang H*. ABIN1 (Q478) is Required to Prevent Hematopoietic Deficiencies through Regulating Type I IFNs Expression. Adv Sci (Weinh) 2023 Nov 27:e2303555.
4. Wang L, Zhang X, Zhang H, Lu K, Li M, Li X, Ou Y, Zhao X, Wu X, Wu X, Liu J, Xing M, Liu H, Zhang Y, Tan Y, Li F, Deng X, Deng J, Zhang X, Li J, Zhao Y, Ding Q, Wang H, Wang X*, Luo Y*, Zhou B*, Zhang H*. Excessive apoptosis of Rip1-deficient T cells leads to premature aging. EMBO Rep 2023 Nov 15:e57925.
5. Xinyu Wang, Qian Wen, Yanjun Wu, Jingwen Kong, Keying Xu, Jiazheng Jiao, Haibing Zhang*, Kai Wang*, Xiao Xu*, Lixing Zhan*. Polarity protein AF6 functions as a modulator of necroptosis by regulating ubiquitination of RIPK1 in liver diseases. Cell Death Dis 2023 Oct 12;14(10):673.
6. Du L, Wu Y, Pan Y, Wang L, Zhang H, Li J, Liu Y, Zhang H*, He P*. Lipopolysaccharide and Glycolipoprotein Coordinately Triggered Necroptosis Contributes to the Pathogenesis of Leptospira Infection in Mice. J Infect Dis 2023 Oct 3;228(7):944-956.
7. Sun M^#, Ma X^#, Mu W^#, Li H, Zhao X, Zhu T, Li J, Yang Y, Zhang H*, Ba Q*, Wang H*. Vemurafenib inhibits necroptosis in normal and pathological conditions as a RIPK1 antagonist. Cell Death Dis 2023 Aug 24;14(8):555.
8. Li M, Liu Y, Xu C, Zhao Q, Liu J, Xing M, Li X, Zhang H, Wu X, Wang L, Ou Y, Wu X, Zhao X, Liu H, Qiu L, Li F, Li J, Rong W, Luo Y, Deng J, Wang X, Wang Z, Zhao Y, Lv A, Li Q, Zhang H*. Ubiquitin-binding domain in ABIN1 is critical for regulating cell death and inflammation during development. Cell Death Differ 2022 Oct;29(10):2034-2045.
9. Li X^#, Li F^#, Zhang X, Zhang H, Zhao Q, Li M, Wu X, Wang L, Liu J, Wu X, Ou Y, Xing M, Zhang Y, Deng J, Wang X, Luo Y, Li J, Zhao Y, Zhang H*. Caspase-8 auto-cleavage regulates programmed cell death and collaborates with RIPK3/MLKL to prevent lymphopenia. Cell Death Differ 2022 Aug;29(8):1500-1512.
10. Zhang H, Wu X, Li M, Li X, Wang L, Liu J, Ou Y, Wu X, Xing M, Li F, Zhao X, Liu H, Jones C, Deng J, Xie Q, Zhang Y, Luo Y, Zhao Y, Zhang H*. Caspase-8 Blocks Receptor-Interacting Protein Kinase-1 Kinase-Independent Necroptosis during Embryogenesis. Immunohorizons 2022 Jul 20;6(7):465-475.
11. Rong W^#, Liu C^#, Li X, Wan N, Wei L, Zhu W, Bai P, Li M, Ou Y, Li F, Wang L, Wu X, Liu J, Xing M, Zhao X, Liu H, Zhang H*, Lyu A*. Caspase-8 Promotes Pulmonary Hypertension by Activating Macrophage-Associated Inflammation and IL-1β (Interleukin 1β) Production. Arterioscler Thromb Vasc Biol 2022 May;42(5):613-631.
12. Zhang Y, Li M, Li X, Zhang H, Wang L, Wu X, Zhang H*, Luo Y*. Catalytically inactive RIP1 and RIP3 deficiency protect against acute ischemic stroke by inhibiting necroptosis and neuroinflammation. Cell Death Dis 2020 Jul 23;11(7):565.
13. Zhang H^#, Wu XX^#, Li XM, Li M, Li F, Wang LX, Zhang XX, Zhang Y, Luo Y, Zhang H*. Crucial role of the Receptor-interacting protein homotypic interaction motifs (RHIM) of RIPK3 in RIPK1 dependent cell death and lymphoproliferative disease. Cell Rep 2020 May 19;31(7):107650.
14. Zhang XX^#, Zhang HW^#, Xu CX, Li XM, Li M, Wu XX, Pu WJ, Zhou B, Wang HK, Li DL, Ding QR, Ying H, Wang H, Zhang H*. Ubiquitination of RIPK1 suppresses programmed cell death by regulating RIPK1 kinase activation during embryogenesis. Nat Commun 2019 Sep 13;10(1):4158.
15. Zhao Q^#, Yu X^#, Li M, Liu Y, Han Y, Zhang X, Li XM, Wu X, Qin J, Fang J, Zhang H*. MLKL attenuates colon inflammation and colitis-tumorigenesis via suppression of inflammatory responses. Cancer Lett 2019 Sep 10;459:100-111.
16. Zhang X, Zhang H*. Chemotherapy drugs induce pyroptosis through caspase-3-dependent cleavage of GSDME. Sci China Life Sci 2018 Jun;61(6):739-740.
17. Xu C, Wu X, Zhang X, Xie Q, Fan C, Zhang H*. Embryonic lethality and host immunity of RelA-deficient mice is mediated by both apoptosis and necroptosis. J Immunol 2018 Jan 1;200(1):271-285.
18. Liu Y^#, Fan C^#, Zhang Y, Yu X, Wu X, Zhang X, Zhao Q, Zhang H, Xie Q, Li M, Li X, Ding Q, Ying H, Li D, Zhang H*. RIP1 Kinase Activity dependent roles in embryonic development of Fadd-deficient mice. Cell Death Differ 2017 Aug;24(8):1459-1469.
19. Yu X^#*, Zhao Q^#, Zhang X, Zhang H, Liu Y, Wu X, Li M, Li X, Zhang J, Ruan X, Zhang H*. Celastrol ameliorates inflammation through inhibition of NLRP3 inflammasome activation. Oncotarget 2017 Jun 27;8(40):67300-67314.
20. Zhao Q, Yu X, Zhang H, Liu Y, Zhang X, Wu X, Xie Q, Li M, Ying H, Zhang H*. RIPK3 Mediates Necroptosis during Embryonic Development and Postnatal Inflammation in Fadd-Deficient Mice. Cell Rep 2017 Apr 25;19(4):798-808.
21. Zhang X^#, Fan C^#, Zhang H, Zhao Q, Liu Y, Xu C, Xie Q, Wu X, Yu X, Zhang J, Zhang H*. MLKL and FADD are Critical for Suppressing Progressive Lymphoaccumulative Disease and Activating NLRP3 Inflammasome. Cell Rep 2016 Sep 20;16(12):3247-3259.
22. Fan C^#, Pu W^#, Wu X, Zhang X, He L, Zhou B*, Zhang H*. Lack of FADD in Tie-2 expressing cells causes RIPK3-mediated embryonic lethality. Cell Death Dis 2016 Sep 1;7(9):e2351.
23. Yu X, Zhao Q, Zhang H, Fan C, Zhang X, Xie Q, Xu C, Liu Y, Wu X, Han Q*, Zhang H*. Gambogenic acid inhibits LPS-simulated inflammatory response by suppressing NF-κB and MAPK in macrophages. Acta Biochim Biophys Sin 2016 May;48(5):454-461.
24. Zhang H, Zhang X, Fan C, Xie Q, Xu C, Zhao Q, Liu Y, Wu X, Zhang H*. A novel sgRNA selection system for CRISPR-Cas9 in mammalian cells. Biochem Biophys Res Commun 2016 Mar 18;471(4):528-532.
25. Zhang H, Zhou X, McQuade T, Li J, Chan FK*, Zhang J*. Functional complementation between FADD and RIP1 in embryos and lymphocytes. Nature 2011 Mar 17;471(7338):373-376.
26. Zhang H^#, Hou YJ^#, Han SY, Zhang EC, Huebner K, Zhang J*. Mammalian nitrilase 1 homologue Nit1 is a negative regulator in T cells. Int Immunol 2009 Jun;21(6):691-703.
27. Zhang H, Rosenberg S, Coffey FJ, He YW, Manser T, Hardy RR, Zhang J*. A role for cFLIP in B cell proliferation and stress MAPK regulation. J Immunol 2009 Jan 1;182(1):207-215.