职称：教授
职务：细胞与发育生物学系系主任和消化研究所科研所长
电话：021-31246730
邮箱：stevenhou@fudan.edu.cn
地址：幸福宝导航app入口A401-7
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。
主要研究方向
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。
本课题组现面向海内外公开招聘青年研究员和博士后，欢迎有志向的青年才俊加入。
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
授课情况
干细胞与发育，发育与代谢，细胞发育与健康
招生专业
细胞生物学，发育生物学，遗传学
代表性成果
Wang, G., Yin, W., Shin, H., Tian, Q., Lu, W., and Hou, S. X. (2021). Neuronal accumulation of peroxidated lipids promotes demyelination and neurodegeneration through the activation of the microglial NLRP3 inflammasome. Nat Aging, 1, 1024-1037.
Wang, G., Xu, J., Zhao, J., Yin, W., Liu, D., Chen, W., and Hou, S. X. (2020).Arf1-mediated Lipid Metabolism Sustains Cancer Stem Cells and Its ablation Induces Anti-tumor Immune Responses in Mice. Nat Commun. 220. (Editors' Highlights)
Singh, S. R., Zeng, X., Zhao, J., Liu, Y., Hou, G., Liu, H, and Hou, S. X. (2016). The Lipolysis Pathway Sustains Normal and Transformed Stem Cells in Adult Drosophila.Nature 538, 109-113.
Liu, Y, Ge, Q., Chan, B., Liu, H., Singh, S. R., Manley, J., Lee, J., Weidenman, A. M., Hou, G., and Hou, S. X. (2016). Whole-animal genome-wide RNAi screen identifies networks regulating male germline stem cells in Drosophila. Nat Commun. 7:12149. doi: 10.1038/ncomms12149.
Singh, S. R., Liu, Y., Zhao, J., Zeng, X., and Hou, S. X. (2016). The novel tumour suppressor Madm regulates stem cell competition in the Drosophila testis. Nat Commun. 7:10473. doi: 10.1038/ncomms10473.
Zeng, X., Han, L., Singh, S. R., Liu, H., Neumüller, R. A., Yan, D., Hu, Y., Liu, Y., Liu, W., Lin, X., and Hou, S. X. (2015). Genome-Wide RNAi Screen Identifies Networks Involved in Intestinal Stem Cell Regulation in Drosophila. Cell Reports 10, 1226-1238.
Zeng, X., and Hou, S. X. (2015). Enteroendocrine cells are generated from stem cells through a distinct progenitor in the adult Drosophila posterior midgut.Development 142(4), 644-653.
Zeng, X., Lin, X., and Hou, S. X. (2013). The Osa-containing SWI/SNF chromatin-remodeling complex regulates stem cell commitment in the adult Drosophila intestine.Development 140(17), 3532-3540.
Zeng, X., and Hou, S. X. (2012). Broad relays hormone signals to regulate stem cell differentiation in Drosophila midgut during metamorphosis. Development 139(21), 3917-3925.
Zeng, X., and Hou, S. X. (2011). Kidney stem cells found in adult zebrafish. Cell Stem Cell 8(3), 247-249.
Ande, S., Orri, K., Chen, X., Coppola, V., Tessarollo, L., Keller, J. R., and Hou, S. X. (2010). RapGEF2 is essential for embryonic hematopoiesis but dispensable for adult hematopoiesis. Blood. 116, 2921-2931.
Singh, S. R., Liu, W., and Hou, S. X. (2007). The adult Drosophila Malpiphian Tubules are maintained by multipotent stem cells. Cell Stem Cell1(2), 191-203.
Wang, H., Singh, S. R., Zheng, Z. Y., Oh, S. W., Chen, X., Edwards, K., and Hou, S. X. (2006).A Rap-GEF/Rap GTPase signaling controls stem cell maintenance through regulating adherens junction positioning and cell adhesion in Drosophila testis.Dev. Cell 10, 117-126.
Singh, S. R., Chen, X., and Hou, S. X. (2005). JAK/STAT signaling regulates tissue outgrowth and male germline stem cell fate in Drosophila. Cell Research 15(1), 1-5.
Chen, X., Oh, S. W., Zheng, Z., Chen, H. W., Shin, H. H., and Hou, S. X. (2003).Cyclin D-Cdk4 and Cyclin E-Cdk2 regulate the JAK/STAT signal transduction pathway in Drosophila. Dev. Cell 4, 179-190.
Hou, S. X., Zheng, Z., Chen, X., and Perrimon, N. (2002). The JAK/STAT pathway in model organisms: Emerging roles in cell movement. Dev. Cell 3, 765-778.
Chen, H. W., Chen, X., Oh, S. W., Marrinissen, M. J., Gutkind, J. S., and Hou, S. X. (2002). mom identifies a receptor for the Drosophila JAK/STAT signal transduction pathway and encodes a protein distantly related to the mammalian cytokine receptor family. Genes Dev. 16, 388-398, 2002.
Hou, S. X., Goldstein, E. S., and Perrimon, N. (1997). Drosophila Jun relays the JNK signal transduction pathway to the DPP signal transduction pathway in regulating epithelial cell sheet movement. Genes Dev. 11, 1728-1737, 1997.
Hou, S. X., Melnick, M. B., and Perrimon, N. (1996). Marelle acts downstream of the Drosophila Hop/JAK kinase and encodes a protein similar to the mammalian STATs. Cell 84, 411-419.
Hou, S. X., Chou, T. B., Melnick, M. B., and Perrimon, N.(1995). The torso receptor tyrosine kinase activates raf in a Ras-independent pathway. Cell 81, 63-71.