Jian Zhu

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

Lab Homepage:https://www.bio.pku.edu.cn/homes/Index/news_cont_jl/16/51.html

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. Li, J.*, Zhang, Y.*, Peng, J.*, Yang, W.*, Pan, Y., Xu, Y., Yao, J., Lin, S., Li, Y., Gu, X., Dong, W., Yu, X., Ge, M.#, Liu, M.# and Zhu, A. J.# (2025) A regulator of amino acid sensing links lipid peroxidation and lipid droplet-dependent antioxidant response. Molecular Cell, 85: 3225-3240. doi: 10.1016/j.molcel.2025.08.009

2. Gao, Y.*, Feng, J.*, Zhang, Y, Yi, M., Zhang, L., Yan, Y., Zhu, A. J.# and Liu, M.# (2024) Ehbp1 orchestrates orderly sorting of Wnt/Wingless to the basolateral and apical cell membranes. EMBO Report, 25: 5053-5079. doi: 10.1038/s44319-024-00289-1

3. Wang, Y., Zhou, J., Yang, Q., Li, X., Oiu, Y., Zhang, Y.#, Liu, M.# and Zhu, A. J.# (2024) Therapeutic siRNA targeting PLIN2 ameliorates steatosis, inflammation, and fibrosis in steatotic liver disease models. Journal of Lipid Research, 65: 100635. doi: 10.1016/j.jlr.2024.100635

4. He, T.*, Fan, Y.*, Du, J., Yi, M., Li, Y., Liu, M.# and Zhu, A. J.# (2023) Stuxnet fine-tunes Notch dose during development using a functional Polycomb response element. Development, 150: dev201297. doi: 10.1242/dev.201297

5. Zhang, Y.*, Lin, S.*, Peng, J.*, Liang, X., Yang, Q., Bai, X., Li, Y., Li, J., Dong, W., Wang, Y., Huang, Y., Pei, Y., Guo, J., Zhao, W., Zhang, Z., Liu, M.# and Zhu, A. J.# (2022) Amelioration of hepatic steatosis by dietary essential amino acid-induced ubiquitination. Molecular Cell, 82: 1528-1542. doi: 10.1016/j.molcel.2022.01.021

6. Liu, M.*, Liu, A.*, Wang, J.*, Zhang, Y., Li, Y., Su, Y.# and Zhu, A. J.# (2020) Competition between two phosphatases fine-tunes Hedgehog signaling. Journal of Cell Biology, 220: e202010078. doi: 10.1083/jcb.202010078

7. 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. doi: 10.1016/j.devcel.2016.05.013

8. 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. doi: 10.7554/eLife.17200

9. 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. doi: 10.1242/dev.099564

10. 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. doi: 10.1126/scisignal.2001747