2014-至今，研究员，中科院上海生物化学与细胞生物学研究所

　　2009-2014，博士后，美国西南医学中心/北京生命科学研究所

　　2005-2009，博士，北京生命科学研究所

　　2001-2005，学士，北京师范大学

　　程序性细胞死亡对于个体发育，机体稳态维持及病理过程等诸多方面都有着重要作用。它主要包括凋亡、坏死和自噬等方式。其中，细胞坏死长期以来都被认为是一种被动且不可调控的过程。然而近几年研究表明细胞坏死也是受到精密调控的。不同于细胞凋亡(apoptosis)，细胞坏死(necrosis)会激活机体的免疫应答，机体局部的细胞坏死会引起全局性的生理病理反应。因此它参与了众多病理过程，例如病毒感染(viral infection)的免疫激活，缺血性坏死损伤(ischemic injuries)，以及神经退行性疾病(neurodegenerative disease)发生及发展等等。相对于研究较为成熟的细胞凋亡，细胞坏死还是一个崭新的领域。

　　程序性细胞坏死是一种由激酶的激活而引发的细胞死亡方式。死亡受体(例如TNFR1)的激活最终可以诱发程序性细胞坏死，而起动细胞坏死的信号转导主要依赖于激酶RIP1和RIP3的调控。细胞坏死发生之后，RIP1与RIP3相结合并激活了RIP3的激酶活性，然后RIP3发生自身磷酸化，使其可以特异性的和底物MLKL相结合，MLKL进而被RIP3磷酸化。这时的RIP1/RIP3/MLKL形成一个有活性的细胞坏死复合体，传递死亡信号给下游，使细胞坏死得以最终发生。

　　本实验室的研究目标是阐明细胞坏死的分子机制和相关疾病的病理机制。我们欢迎对细胞死亡有兴趣的你的加入!

1. 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
2. Sun L*. Amyloids as kinase signalling platforms. Nature Reviews Molecular Cell Biology, 2023, 24(2), 85.
3. 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
4. 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
5. 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.
6. 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.
7. 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.
8. Zhang J, Yang Y, He W, Sun L*. Necrosome core machinery: MLKL. Cellular and Molecular Life Sciences, 2016, 73(11-13), 2153-2163.
9. 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.
10. 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
11. Wang H, Sun L, Su L, Rizo J, Liu L, Wang LF, Wang FS, Wang X*. Mol Cell, 2014, 54, 133-146.
        *Cover story. Story of this work was selected by Faculty of 1000 Biology
12. 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.
13. 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.
14. 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.
15. Hildebrand JM, Sun L, Silke J*. An appointment with death,生死有时: 2013 Cold Spring Harbor Asia meeting ‘Mechanisms and Functions of Non- Apoptotic Cell Death’. Cell Death & Differ, 2013, 20, 1593-4.
16. 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.
17. 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

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