侯宪玉 - 复旦大学 - 生命科学学院

个人简介

1983年获兰州大学化学学士学位，1986年获上海生物化学研究所硕士学位，1994年获美国芝加哥大学分子遗传与细胞生物学博士学位。此后在哈佛医学院Howard Hughes医学研究所从事博士后研究。1997-2019年在美国国家癌症研究所分别担任Tenure-track研究员，终身资深研究员和干细胞调控与动物衰老实验室主任。2020年起做为国家海外高层次引进人才和特聘专家任职于复旦大学生命科学院并在代谢与整合生物学研究院和中山医院双聘。荣誉及获奖情况 2017美国国立卫生研究所科学突破团队奖 2009美国国家癌症研究所所长创新奖 2006关于肿瘤抑制基因BHD的研究被选为美国国家癌症研究所年度最佳成果 2001美国国家癌症研究所研究员奖 2000美国陆军乳腺癌研究奖 1997 Charles Harkin (查尔斯·哈金)癌症研究奖，美国 1995美国白血病学会博士后奖学金 1994美国NIH博士后奖学金奖

研究领域

干细胞、脂代谢与免疫应答在发育、肿瘤和神经退行性疾病中的相互作用。干细胞是正常生物发育和衰老的中心细胞，是再生医学的关键资源。肿瘤干细（CSCs）存在于大多数肿瘤中，是导致肿瘤转移，疾病复发以及患者最终死亡的祸根。我们对干细胞的维持，质量调控和与外部环境间的信号传递所知甚少。在不久前发表于Nature上的论文中，我们发现干细胞（包括癌症干细胞）具有代谢独特性，就像冬眠动物，主要依赖于脂质储备的能量。阻断COPI/Arf1介导的脂质代谢能选择性地影响干细胞，导致脂滴积聚，代谢应激，功能缺陷（蛋白质聚集体）并最终坏死。近期发表于Nature Communications的论文中，我们在荷瘤小鼠中确定了详细的分子机制，阻断Arf1通路可以起到一石二鸟的效果：不仅能杀死CSCs，还会释放危险信号而改变肿瘤微环境并引发肿瘤特异性免疫反应，将死亡的CSCs转化为治疗性疫苗以吸引并激活免疫细胞来破坏大块肿瘤从而达到治疗的持久功效。我们最近的研究发现Arf1介导的脂质代谢也维持着神经元的功能 (Nature Aging 2021)。Arf1在小鼠神经元中的特异敲除会引发一系列反应:脂滴积聚、线粒体损伤、过氧化脂质形成并扩散到小胶质细胞而激活炎症小体、细胞因子释放和补体系统激活等，最终会导致神经元脱髓鞘和神经退行性疾病。这与我们在神经退行性患者样品中发现的Arf1的减少会诱导神经炎症通路的现象相一致，特别是在多发性硬化症（MS）、肌萎缩性侧索硬化症（ALS）和老年痴呆症 (AD)中。该研究建立首个由脂代谢紊乱和过氧化脂质形成引发的神经退行性疾病的动物模型，揭示了神经退行性疾病治疗的可能新靶点，并提示脂滴积累与神经退行间的联系。

近期论文

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