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  • 孫麗明
  • 研究員，研究組長，博士生導(dǎo)師
  • E-mail: liming.sun@@sibcb.ac.cn
  • 實(shí)驗(yàn)室主頁: https://sun-lab.sibcb.ac.cn/
    個(gè)人簡介：

  • 　　2014-至今，研究員，中科院上海生物化學(xué)與細(xì)胞生物學(xué)研究所

    　　2009-2014，博士后，美國西南醫(yī)學(xué)中心/北京生命科學(xué)研究所

    　　2005-2009，博士，北京生命科學(xué)研究所

    　　2001-2005，學(xué)士，北京師范大學(xué)

    社會(huì)任職：
    研究方向：
  • 細(xì)胞壞死的分子基礎(chǔ)與相關(guān)疾病機(jī)理
    研究工作：

  • 　　程序性細(xì)胞死亡對(duì)于個(gè)體發(fā)育，機(jī)體穩(wěn)態(tài)維持及病理過程等諸多方面都有著重要作用。它主要包括凋亡、壞死和自噬等方式。其中，細(xì)胞壞死長期以來都被認(rèn)為是一種被動(dòng)且不可調(diào)控的過程。然而近幾年研究表明細(xì)胞壞死也是受到精密調(diào)控的。不同于細(xì)胞凋亡(apoptosis)，細(xì)胞壞死(necrosis)會(huì)激活機(jī)體的免疫應(yīng)答，機(jī)體局部的細(xì)胞壞死會(huì)引起全局性的生理病理反應(yīng)。因此它參與了眾多病理過程，例如病毒感染(viral infection)的免疫激活，缺血性壞死損傷(ischemic injuries)，以及神經(jīng)退行性疾病(neurodegenerative disease)發(fā)生及發(fā)展等等。相對(duì)于研究較為成熟的細(xì)胞凋亡，細(xì)胞壞死還是一個(gè)嶄新的領(lǐng)域。

    　　程序性細(xì)胞壞死是一種由激酶的激活而引發(fā)的細(xì)胞死亡方式。死亡受體(例如TNFR1)的激活最終可以誘發(fā)程序性細(xì)胞壞死，而起動(dòng)細(xì)胞壞死的信號(hào)轉(zhuǎn)導(dǎo)主要依賴于激酶RIP1和RIP3的調(diào)控。細(xì)胞壞死發(fā)生之后，RIP1與RIP3相結(jié)合并激活了RIP3的激酶活性，然后RIP3發(fā)生自身磷酸化，使其可以特異性的和底物MLKL相結(jié)合，MLKL進(jìn)而被RIP3磷酸化。這時(shí)的RIP1/RIP3/MLKL形成一個(gè)有活性的細(xì)胞壞死復(fù)合體，傳遞死亡信號(hào)給下游，使細(xì)胞壞死得以最終發(fā)生。

    　　本實(shí)驗(yàn)室的研究目標(biāo)是闡明細(xì)胞壞死的分子機(jī)制和相關(guān)疾病的病理機(jī)制。我們歡迎對(duì)細(xì)胞死亡有興趣的你的加入!

    承擔(dān)科研項(xiàng)目情況：
    代表論著：
    1. Abu-Remaileh M, Chan C, Chen L, Demirer G, Fiszbein A, Jug F, Lechuga-Vieco A, Luisier R, Pagan J, Sabari B, Shao S, Sun L &?ylicz J. Visions of the future of molecular cell biology. Nature Reviews Molecular Cell Biology, 2025, 26, 735-740.
    2. Arama E, Cosentino K, Czabotar P, Gan B, Hartland E, Jiang X, Kagan J, Nagata S, Schroder K, Sun L, Xu D & Yuan J. Towards a molecular and structural definition of cell death. Nature Structural & Molecular Biology, doi :10.1038/s41594-025-01646-x.
    3. Wu E, Wu C, Jia K, Zhou s, and Sun L*. HSPA8 inhibitors augment cancer chemotherapeutic effectiveness via potentiating necroptosis. Molecular Biology of the Cell, 2024, 35(8),1-10.
    4. Marion C. Bonnet* and?Liming Sun, Editorial: Necroptosis: from bench to bedside. Front. Immunol. , 19 June 2024. doi.org/10.3389/fimmu.2024.1441901
    5. Wu E#, He W#, Wu C, Chen Z, Zhou S, Wu X, Hu Z, Jia K, Pan J, Wang L, Qin J, Liu D, Lu J, Wang H, Li J, Wang S, and Sun L *. HSPA8 acts as an amyloidase to suppress necroptosis by inhibiting and reversing functional amyloid formation. Cell Res (2023). https://doi.org/10.1038/s41422-023-00859-3
    6. Sun L*. Amyloids as kinase signalling platforms. Nature Reviews Molecular Cell Biology, 2023, 24(2), 85.
    7. Zhu X, Yang N, Yang Y, Yuan F, Yu D, Zhang Y, Shu Z, Nan N, Hu H, Liu X, Chen S, Sun L* and Wang H*.Spontaneous necroptosis and autoinflammation are blocked by an inhibitory phosphorylation on MLKL during neonatal development. Cell Research. 2021, 32(4), 407-410
      ????*Story of this work was selected by Faculty of 1000 Biology
    8. Zhou S, Zhang W, Cai G, Ding Y, Wei C, Li S, Yang Y, Qin J, Liu D, Zhang H, Shao X, Wang X, Wang H, Yang W, Wang H, Chen S, Hu P* and Sun L*. Myofiber necroptosis promotes muscle stem cell proliferation via releasing Tenascin-C during regeneration. Cell Research. 2020, 30(12), 1063–1077.
      ????*Cover story. Story of this work was selected by Faculty of 1000 Biology
    9. Yang D, Sun Y, Chen J, Zhang Y, Fan S, Huang M, Xie X, Cai Y, Shang Y, Gui T, Sun L, Hu J, Dong J, Yeap LS, Wang X, Xiao W, Meng FL*. REV7 is required for processing AID initiated DNA lesions in activated B cells. Nat Commun, 2020, 11(1), 2812.
    10. Zhang J, Yang Y, Zhou S, He X, Cao X, Wu C, Hu H, Qin J, Wei G, Wang H, Liu S* and Sun L*. Membrane-bound TNF mediates microtubule-targeting chemotherapeutics-induced cancer cytolysis via juxtacrine inter-cancer-cell death signaling. Cell Death & Differ, 2020, 27(5), 1569–1587.
    11. Ran Y, Su Y, Sun L, He S, Meng L, Liao D, Ma Y, Liu C, Li S, Ruan H, Lei X, Wang X* and Zhang Z*. Discovery of a Highly Potent, Selective, and Metabolically Stable Inhibitor of Receptor-Interacting Protein 1 (RIP1) for the Treatment of Systemic Inflammatory Response Syndrome. J Med Chem, 2017, 60(3), 972-986.
    12. Zhang J, Yang Y, He W, Sun L*. Necrosome core machinery: MLKL. Cellular and Molecular Life Sciences, 2016, 73(11-13), 2153-2163.
    13. Sun L* and Wang X. A new kind of cell suicide: mechanisms and functions of programmed necrosis. Trends in biochemical sciences. 2014, 39(12), 587-593.
    14. Su L, Quade B, Wang H, Sun L, Wang X, Rizo J*. (2014) A Plug Release Mechanism for Membrane Permeation by MLKL. Structure, 2014, 22(10): 1489-1500
    15. Wang H, Sun L, Su L, Rizo J, Liu L, Wang LF, Wang FS, Wang X*. Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3.?Mol Cell, 2014, 54, 133-146.
      ????*Cover story. Story of this work was selected by Faculty of 1000 Biology
    16. Sun L, Wang H, Wang Z, He S, Chen S, Liao D, Wang L, Yan J, Liu W, Lei X*, and Wang X*. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell, 2012,148, 213-227.
      ????*Research of this work was highlighted in Cell, Nature Reviews Molecular Cell Biology, and Chem. & Eng. News. Story of this work was selected by Faculty of 1000 Biology.
    17. Liao D, Sun L, Liu W, He S, Wang X, Lei X*. Necrosulfonamide Inhibits Necroptosis by Selectively Targeting the Mixed Lineage Kinase Domain-like Protein. Med. Chem. Commun., 2014, 5, 333-337.
    18. Li S, Zhang L, Yao Q, Li L, Dong N, Rong J, Gao W, Ding X, Sun L, Chen X, Chen S* and Shao F*. Pathogen blocks host death receptor signalling by arginine GlcNAcylation of death domains. Nature, 2013,501, 242-6.
    19. Hildebrand JM, Sun L, Silke J*. An appointment with death,生死有時(shí): 2013 Cold Spring Harbor Asia meeting ‘Mechanisms and Functions of Non- Apoptotic Cell Death’. Cell Death & Differ, 2013, 20, 1593-4.
    20. Sun L, Wang H, Hu J, Han J, Matsunami H, Luo M*. Guanylyl cyclase-D in the olfactory CO2 neurons is activated by bicarbonate. Proc Natl Acad Sci U S A, 2009,106, 2041-2046.
    21. Luo M*, Sun L*and Hu J*. Neural detection of gases--carbon dioxide, oxygen--in vertebrates and invertebrates. Curr Opin Neurobiol, 2009, 19, 354-361.
      ????*Corresponding author
    獲獎(jiǎng)及榮譽(yù)：
    研究組成員：

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