医学创新论坛第52期

CIMR Wednesday Lecture Series

时间：2024年12月11日（周三）下午16:00

地点：首都医科大学基础科研楼北楼一层逸夫报告厅

主持人：何文辉

首都医学科学创新中心

报告人：孙丽明

中国科学院分子细胞科学卓越创新中心 研究员

报告题目：

When dying is not the end: the physiological roles and checkpoints of necroptosis

摘要：

Dr. Sun’s research primarily focused on the molecular mechanism of necroptosis signaling, and its relevance to human diseases. Her major scientific contributions include: (1) Discovered MLKL as a key component of necroptosis pathway at the downstream of RIP3; (2) Identified the autophosphorylation site on RIP3, which is required for MLKL recruitment; (3) Identified the phosphorylation sites on MLKL that are catalyzed by RIP3, which are required for releasing its autoinhibition; (4) Screened out new necroptosis inhibitor NSA, and defined its targeting site on human MLKL-Cys86; (5) Developed monoclonal antibodies that specifically recognize p-RIP3 or p-MLKL, which potentially serve as important tools to dissect necroptosis signaling in vivo; (6) Found microtubule-targeting agents (MTAs) utilize membrane bound-TNF to kill the adjacent tumor cells, which reframed our fundamental understanding on how MTA drugs utilize the tight contact between solid tumor cells to induce cancer-cell-to-cancer-cell killing and eventually shrink the entire tumor with “snowball” effect; (7) Identified Tenascin-C (TNC), released by necroptotic myofibers, as a key factor to promote muscle stem cell (MuSC) proliferation through directly stimulating EGF receptor (EGFR) cascade in MuSCs during regeneration, which provided us a paradigm for understanding that necroptosis, as a form of “altruistic ***”, contributing the conditional niche for adult stem cell proliferation upon injury; (8) Identified a novel phosphorylation site of MLKL that blocks necroptosis-induced systemic inflammation during mouse development, which provided the direct evidence that the spontaneous activation of necroptosis and the potential non-cell death role of MLKL during development; (9) Identified HSPA8 that functions as an "amyloidase," preventing necroptosis by reversing functional amyloid production.

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