研究方向:
发育和代谢疾病致病基因的筛选和作用机制研究
在个体发育、成体稳态维持、衰老与死亡等一系列发育过程中,发育信号有序的产生和时空特异性的表达与调控,共同决定细胞命运决定、分化与死亡。已有发育信号转导的重要发现多集中于下游端事件,缺乏对初始上游端事件的研究。我们利用果蝇翅的形态建成为研究模型,结合经典发育、遗传学手段以及基因编辑和体细胞克隆分析技术,规避因胚胎早期致死而无法后续研究的束缚,研究了在表观遗传、小RNA、RNA可变剪接、蛋白翻译后修饰、代谢调控、跨膜转运等多个层次上调控信号转导通路的上游关键因子及其作用机理。由于这些信号转导通路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,我们的中长期目标是解析这些信号调控网络与发育异常以及肿瘤发生和代谢疾病的相关性,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.Zhao X, Liu B, He T, Zhu AJ, Zhao Z and Du J (2019) Epigenetic regulator Stuxnet modulates octopamine effect on sleep through a Stuxnet-Polycomb- Octb2R cascade. EMBO Reports (in revision).
2.Wang LC, Liao LX, Lv HN, Liu D, Dong W, Zhu AJ, Chen JF, Shi ML, Fu G, Song XM, Jiang Y, Zeng KW and Tu PF (2017) Highly selective activation of heat shock protein 70 by allosteric regulation provides an insight into efficient neuroinflammation inhibition. EBioMedicine 23: 160-172.
3.Du J, Zhang J, He T, Li Y, Su Y, Tie F, Liu M, Harte PJ and Zhu AJ (2016) Stuxnet facilitates the degradation of Polycomb protein during development. Developmental Cell 37: 507-519. (Cover article)
4.Liu M, Li Y, Liu A, Li R, Su Y, Du J, Li C and Zhu AJ (2016) The exon junction complex regulates the splicing of cell polarity gene dlg1 to control Wingless signaling in development. eLIFE 5: e17200. (Cover article)
5.Zhang J, Du J, Lei C, Liu M and Zhu AJ (2014) UBPY controls the stability of the ESCRT-0 subunit Hrs in development. Development 141:1473-1479.
6.Geisbrecht E, Sawant K, Su Y, Liu Z, Silver DL, Burtscher A, Wang X, Zhu AJ and McDonald JA (2013) Genetic interaction screens identify a role for hedgehog signaling in Drosophila border cell migration. Developmental Dynamics 242: 414-431.
7.Zhang J, Liu M, Su Y, Du J and Zhu AJ (2012) A targeted in vivo RNAi screen reveals deubiquitinases as new regulators of Notch signaling. Genes Genomics Genetics 2: 1563-1575. (Cover article)
8.Su Y, Ospina JK, Zhang J, Michelson A, Schoen AM and Zhu AJ (2011) Sequential phosphorylation of Smoothened transduces graded Hedgehog signaling. Science Signaling 4: ra43.