朱健
电子邮件: zhua (at) pku (dot) edu (dot) cn;
实验室主页: http://www.bio.pku.edu.cn/teacher_dis_oa.php?cid=146&&teaid=104
研究方向:
个体发育和疾病发生中信号转导网络的时空调控
关键词:信号转导,表观遗传,小RNA,RNA可变剪切,翻译后加工,膜泡运输,代谢调控,轴突导向,果蝇,线虫,小鼠
在个体发育、衰老与再生过程中,多个信号转导途径协同作用,共同调控细胞命运决定、分化与死亡。本实验室运用经典发育遗传学与细胞生物学和生物化学紧密结合的研究手段,揭示在表观遗传、小RNA、RNA可变剪切、蛋白修饰及跨膜转运等多个层次上调控信号转导途径的关键因子及其作用机理。黑腹果蝇做为一个经典的模式生物,在信号转导研究领域发挥了重要作用。在果蝇各个组织器官中,翅的发育不仅受到多种信号转导途径的综合调控,而且其高度统一的发育程式非常适合用于遗传筛选。本实验室目前采用果蝇翅的发育作为模式系统来研究信号转导途径调控网络及作用原理。由于这些信号转导途径从无脊椎到脊椎动物高度保守,并且在干细胞命运决定、个体衰老、机体代谢及肿瘤发生中起关键作用,实验室的中长期目标是解析这些信号途径调控网络与小鼠和人的发育异常以及疾病发生的相关性,从而用于疾病的诊断,药物靶点的开发和治疗。
代表性科研论文:
1. Liu, M., Li, Y., Liu, A., Li, R., Su, Y., Du, J., Li, C. and Zhu, A. J. (2016) The exon junction complex regulates the splicing of cell polarity gene dlg1 to control Wingless signaling in development. eLife, 5: e17200.
2. Du, J., Zhang, J., He, T., Li, Y., Su, Y., Tie, F., Liu, M., Harte, P. J. and Zhu. A. J. (2016) Stuxnet facilitates the degradation of Polycomb protein during development. Developmental Cell, 37: 507-519 (Cover featured article).
Commented in Developmental Cell.
Karch, F. (2016) Stuxnet recruits the proteasome to take down Polycomb. Developmental Cell, 37: 485-486.
Commented in Science China Life Sciences.
Wu, X. (2016) Stuxnet detected, Pc breaks down. Science China Life Sciences, doi: 10.1007/s11427-016-5108-4
3. Zhang, J., Du, J., Lei, C., Liu, M. and Zhu, A. J. (2014) UBPY controls the stability of the ESCRT-0 subunit Hrs in development. Development, 141: 1473-1479.
4. Geisbrecht, E. R., Sawant, K., Su, Y., Liu, Z., Silver, D. L., Burtscher, A., Wang, X., Zhu, A. J. and McDonald J. A. (2013) Genetic interaction screens identify a role for Hedgehog signaling in Drosophila border cell migration. Developmental Dynamics, 242: 414-431.
5. Zhang, J., Liu, M., Su, Y., Du, J. and Zhu, A. J. (2012) A targeted in vivo RNAi screen reveals deubiquitinases as new regulators of Notch signaling. G3 Genes Genomes Genetics, 2: 1563-1575 (Cover featured article).
6. Su, Y., Ospina, J. K., Zhang, J., Michelson, A., Schoen, A. M. and Zhu, A. J. (2011) Sequential phosphorylation of Smoothened transduces graded Hedgehog signaling. Science Signaling, 4: ra43.
Commented in Science Signaling.
VanHook, A. M. (2011) Fine-tuning Hedgehog signaling in development and
disease. Science Signaling, 4: eg10.
7. Du, J., Zhang, J., Su, Y., Liu, M., Ospina, .J. K., Yang, S. and Zhu, A. J. (2011) In vivo RNAi screen reveals neddylation genes as novel regulators of Hedgehog signaling. PLoS One, 6: e2416.
8. Huang X., Suyama, K., Buchanan, J., Zhu, A. J. and Scott, M. P. (2005) A Drosophila model of the Niemann-Pick type C lysosome storage disease: dnpc1a is required for molting and sterol homeostasis. Development, 132: 5115-5124.
9. Zhu, A. J. and Scott, M. P. (2004) Incredible journey: How do developmental signals travel through tissue? Genes & Development, 18: 2985-2997 (Cover featured article).
10. Hwa, J. J.,* Zhu, A. J.,* Hiller, M. A., Kon, C. Y., Fuller, M. T., Santel, A. (2004) Germ-line specific variants of components of the mitochondrial outer membrane import machinery in Drosophila. FEBS Letter, 572: 141-146 (* Co-first author).
11. Zhu, A. J., Zheng, L., Suyama, K. and Scott, M. P. (2003) Altered localization of Drosophila Smoothened protein activates Hedgehog signal transduction. Genes & Development, 17: 1240-1252 (Cover featured article).
Commented in Current Biology.
van den Heuvel, M. (2003) Hedgehog signaling: off the shelf modulation. Current Biology, 13: R686-R688.
12. Zhu, A. J. and Watt, F. M. (1999) β-Catenin signalling modulates proliferative potential of human epidermal keratinocytes independently of intercellular adhesion. Development, 126: 2285-2298.
13. Zhu, A. J., Haase, I. and Watt, F. M. (1999) Signaling via β1 integrins and mitogen-activated kinase determines human epidermal stem cell fate in vitro. Proceedings of National Academy of Sciences of the United States of America, 96: 6728-6733.
14. Zhu, A. J. and Watt, F. M. (1996) Expression of a dominant negative cadherin mutant inhibits proliferation and stimulates terminal differentiation of human epidermal keratinocytes, Journal of Cell Science, 109: 3013-3023.