黑腹果蝇做为一个经典的模式生物，在形态发生素介导的细胞信号转导研究领域中发挥了重要作用。在果蝇各个组织器官中，翅的发育不仅受到多种形态发生素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，以揭示不同信号转导途径的核心元件及这些信号途径的基本作用原理。本实验室目前采用果蝇翅的发育作为模式系统来研究形态发生素介导的信号转导途径及作用原理。由于这些信号通路从无脊椎到高等脊椎动物体内都是高度保守的，并且在发育和疾病（癌症）发生中具有重要作用，本实验室的中长期目标是解析这些信号通路调控机理与哺乳动物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，药物靶点开发和治疗。
The construction of an animal, from a single fertilized egg into myriads, requires exquisite coordination. Remarkably, only a few developmental protein signals are required to operate repeatedly in distinct processes to coordinate cell fate decisions, tissue patterning and organ growth. These signals, which include Hedgehog (Hh), Notch, Wingless/Wnt and growth factors, often act as morphogens signaling over distances of one to tens of cells to induce distinct cellular responses in a concentration-dependent manner. Drosophila melanogaster has been at the forefront of discovery of signaling cascades that are induced by these protein signals. Zhu laboratory chose to utilize the fly wing imaginal disc, the primordium of the adult wing, as a model system not only because the patterning of the wing disc requires interplay between various signaling processes, but also because the stereotypical wing development has been successfully utilized in genetic screens to uncover core components of signaling pathways as well as basic principles of how these signaling processes operate. Owing to the critical roles of signal transduction in development and cancer, most research focuses on the identification of transcriptional targets of these protein signals. In contrast, little is known regarding fundamental mechanisms: 1) that control the expression of core components of signaling cascades, 2) that cells utilize to convert different concentrations of protein signals into distinct developmental signaling outcomes. Zhu laboratory combines classic genetics with rigorous biochemistry and cell biology, and is thereby in a unique position to begin to uncover how developmental protein signals are produced and interpreted in normal development, and go awry in cancer.
代表性论文
1. Zhang, J., Du, J., Lei, C., Liu, M. and Zhu, A. J. , UBPY controls the stability of the ESCRT-0 subunit Hrs in development , Development , 2014 , 141: 1473-1479
2. Geisbrecht, E. R., Sawant, K., Su, Y., Liu, Z., Silver, D. L., Burtscher, A., Wang, X., Zhu, A. J. and McDonald J. A. , Genetic interaction screens identify a role for Hedgehog signaling in Drosophila border cell migration , Developmental Dynamics , 2013 , 242: 414-31.
3. Zhang, J., Liu, M., Su, Y., Du, J. and Zhu, A. J. , A targeted in vivo RNAi screen reveals deubiquitinases as new regulators of Notch signaling. , G3 Genes Genomes Genetics , 2012 , 2: 1563-1575
4. Du, J., Zhang, J., Su, Y., Liu, M., Ospina, .J. K., Yang, S. and Zhu, A. J. , In vivo RNAi screen reveals neddylation genes as novel regulators of Hedgehog signaling , PLoS ONE , 2011 , 6: e2416
5. Su, Y., Ospina, J. K., Zhang, J., Michelson, A., Schoen, A. M. and Zhu, A. J. , Sequential phosphorylation of Smoothened transduces graded Hedgehog signaling , Science Signaling , 2011 , 4: ra43
6. Huang X., Suyama, K., Buchanan, J., Zhu, A. J. and Scott, M. P. , A Drosophila Model of the Niemann-Pick type C lysosome storage disease: dnpc1a is required for molting and sterol homeostasis , Development , 2005 , 132: 5115-5124
7. Hwa, J. J.,* Zhu, A. J.,* Hiller, M. A., Kon, C. Y., Fuller, M. T., Santel, A. , Germ-line specific variants of components of the mitochondrial outer membrane import machinery in Drosophila , FEBS Letter , 2004 , 572: 141-146
8. Zhu, A. J. and Scott, M. P. , Incredible journey: How do developmental signals travel through tissue? , Genes & Development , 2004 , 18: 2985-2997
9. Zhu, A. J., Zheng, L., Suyama, K. and Scott, M. P. , Altered localiDrosophila Smoothened protein activates Hedgehog signal transduction , Genes & Development , 2003 , 17: 1240-1252 (Cover).
10. Zhu, A. J. and Watt, F. M. , β-Catenin signalling modulates proliferative potential of human epidermal keratinocytes independently of intercellular adhesion , Development , 1999 , 126: 2285-2298
11. Zhu, A. J., Haase, I. and Watt, F. M. , 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 , 1999 , 96: 6728-6733
12. Zhu, A. J. and Watt, F. M. , Expression of a dominant negative cadherin mutant inhibits proliferation and stimulates terminal differentiation of human epidermal keratinocytes , Journal of Cell Science , 1996 , 109: 3013-3023
