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Jian Zhu

Jian Zhu


Email:  zhua (at) pku (dot) edu (dot) cn


Lab Homepage: http://www.bio.pku.edu.cn/teacher_dis_oa.php?cid=146&&teaid=104


Research Area:

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. My laboratory chose to utilize the fly wing imaginal disc, the primordium of the adult wing, as a model system for our studies 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, and 2) that cells utilize to translate different concentrations of protein signals into distinct developmental signaling outcomes. My 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 (research direction I) and interpreted (research direction II) in normal development, and go awry in cancer.


Selected Publications:


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.


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