侯宪玉

发布时间:2021-07-14浏览次数:8376

教师基本信息

职称:教授

职务:细胞与发育生物学系系主任

电话:021-31246730

邮箱:stevenhou@fudan.edu.cn

地址:bv伟德国际体育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。1994-1997在哈佛医学院Howard Hughes医学研究所从事博士后研究。1997-2019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年以海外高层次人才引进到复旦大学以特聘教授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

生物体质量维持与衰老病变:新协调细胞死亡调控抗肿瘤免疫、神经退行性病变和衰老

本实验室在过去的20多年里以小鼠和果蝇为模式动物, 主要研究信号传导通路和干细胞在器官发育和稳态维持中的功用, 并获得了多项重要原创性科学发现。以通讯/第一作者NatureCellCell Stem CellDev CellBloodGenes DevNat communNat AgingCell Reports等杂志发表研究论文65篇(包括2Cell1Nature),并申请多项发明专利。实验室培养的人才已有多名在美国和中国做教授。

通过全基因组RNAi 筛选,2016发表的Nature文章报导了一组找到的特异维护干细胞的基因以及缺失引发细胞死亡的新机制。 在干细胞中敲除这组基因首先引起细胞器衰老级联反应,包括脂滴积聚、线粒体损伤、活性氧(ROS)产生、内质网应激和溶酶体蛋白聚集;异常的干细胞然后发送危险信号激活邻近细胞;被激活的邻近细胞最后反馈回来杀死、吞噬并清除受损的干细胞。 不同于所有已知细胞自主的死亡机制,此细胞死亡是通过多个细胞协调完成的, 被命名为“coordinated cell death (CCD)/协调细胞死亡 随后的研究发现在小鼠肿瘤干细胞中敲除或阻断这组基因可诱发肿瘤干细胞应激衰老、释放危险信号并激活系统抗肿瘤免疫反应而有效消除肿瘤,在神经元中敲除或阻断这组基因可诱发神经炎症-免疫反应而导致神经退行性病变,在衰老的“Zombie”细胞中敲除或阻断这组基因可选择清除衰老细胞使机体变得年轻健康。 本课题组现聚焦在揭示新协调细胞死亡的细胞与分子机制并基于此新机制研发全球创新抗肿瘤免疫、逆转神经退行性病变和抗衰老的药物。

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

 

1.       Ma, H., Fang, W., Li, Q., Yuetong Wang, Y., and Hou, S. X. (2023).  Arf1 ablation in colorectal cancer cells activates a super signal complex in DC to enhance anti-tumor immunity.    Adv Sci (Weinh) e2305089. doi: 10.1002/advs.202305089.

 

2.       Wang, G., Jin, S., Liu, J., Li, X., Dai, P., Li, Q., Liu, H., Wang, Y., and Hou, S. X. (2023).   A Neuron-Immune Circuit Regulates Neurodegeneration in the Hindbrain and Spinal cord of ARF1-Ablated Mice.  National Science Review10(12):nwad222. doi: 10.1093/nsr/nwad222.

 

3.       Wang, N.,  Yao, T., Luo, C., Sun, L., Wang, Y., and Hou, S. X. (2023).  Blockade of  Arf1-mediated lipid metabolism in cancers promotes tumor infiltration of cytotoxic T cells via the LPE-PPARγ-NF-kB-CCL5 pathway.  Life Metabolismdoi:10.1093/lifemeta/load036. 

 

4.       Aggarwal, P., Liu, Z., Cheng, G. Q., Singh, S. R., Shi, C., Chen, Y., Sun, L. V., and Hou,  S. X. (2022). Disruption of the lipolysis pathway results in stem cell death through a sterile immunity-like pathway in adult Drosophila.  Cell Rep. 39 (12): 110958.

 

5.       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.

 

6.       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. 11(1):220. doi: 10.1038/s41467-019-14046-9 (Editors' Highlights)

 

7.       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.

 

8.       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.

 

9.       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.

 

10.   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.

 

11.    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. 

 

12.   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.

 

13.   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.

 

14.Zeng, X., and Hou, S. X. (2011). Kidney stem cells found in adult zebrafish. Cell Stem Cell 8(3), 247-249.

 

15.   Singh, S. R., Zeng, X., Zheng, Z., and Hou, S. X. (2011). The adult Drosophila gastric and stomach organs are maintained by a multipotent stem cell pool at the foregut/midgut junction in the cardia (proventriculus). Cell Cycle 10(7), 1109-1120

 

16.   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.

 

17.   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.

 

18.  Singh, S. R., Zhen, W., Zheng, Z. Y., Wang, H.,  Oh, S. W., Liu, W., Zbar, B., Schmidt, L. S., and Hou, S. X. (2006).The Drosophila homologue of the human tumor suppressor gene BHD interacts with the JAK-STAT and Dpp signaling pathways in regulating male germline stem cell maintenance. Oncogene 25, 5933-5941.

 

19.   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.

 

20.   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.

 

21.   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.

 

22.   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.

 

23.   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.

 

24.   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.

 

25.   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.

 

26.   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.