Wenyu Wen, Ph.D

B.S. 2003, Fudan Universi

Ph.D. 2008, Hong Kong University of Science and technology

Postdoc training, 2008, Hong Kong University of Science and technology

Principal Investigator, since 2009, Fudan University

Contact

Institutes of Biomedical Sciences, Fudan University, Shanghai 200032

Tel: +86-21-54237501 (office)

Email: wywen@fudan.edu.cn

Biography

Wenyu received a B.S. degree in Chemistry from Fudan University in 2003, and then joined Dr. Mingjie Zhang’s lab at Hong Kong University of Science and Technology to pursue her Ph.D. degree in the field of neural structural biology, where she characterized the solution structures of proteins (alpha-syntrophin, phospholipase C-gamma1, Rho-kinases, Dynein Light Chain 1, etc.) involved in neuronal signaling and trafficking by NMR. After graduation in the beginning of 2008, Dr. Wen worked as a postdoc in Mingjie’s lab for another year. In 2009, Wenyu joined the Institutes of Biomedical Sciences at Fudan University as a Principal Investigator.

Research Areas

Cell polarity and neural stem cell development

Research Interests

Wen’s research focuses on the molecular mechanism and functional significance of protein complexes regulating cell polarity and neural stem cell development, including asymmetric cell division (ACD) of neural stem cells, neuronal differentiation and migration, and their relationship with neurological diseases (e.g. brain tumor). Her featured accomplishments in recent years are as follows: (1) Asymmetric neural stem cell division and its regulation: Provide the first structural information on the dynamic assembly of LGN-dependent force generators of mitotic spindle orientation during asymmetric neural stem cell division; Discover protein liquid-liquid phase separation (LLPS)-mediated apical localization of the PAR complex and basal localization of cell fate determinant Numb during asymmetric division of neural stem cells. Her research, for the first time, shows that cell polarity establishment and maintenance are controlled by LLPS of biomolecular complexes; (2) Mechanism of proteostasis: Identify the versatile autoinhibitory mechanisms of Nedd4 family ubiquitin ligases, which fine-tune the ligase activities of these E3 enzymes and further regulate neuronal migration as well as tumor cell proliferation and migration. Currently, Wen’s lab is investigating the general role of LLPS in driving reversible neural polarization and brain development, as well as the potential correlation between perturbations of LLPS on neural developmental defects and diseases.

Selected Publications（*corresponding author）:

1. Liu Z, Yang Y, Gu A, Xu J, Mao Y, Lu H, Hu W, Lei QY, Li Z, Zhang M, Cai Y*, Wen W*. (2020) Par complex cluster formation mediated by phase separation. Nature Communications11, 2266.

2. Wang Z, Liu Z, Chen X, Li J, Yao W, Huang S, Gu A, Lei QY, Mao Y, Wen W*. (2019) A multi-lock inhibitory mechanism for fine-tuning enzyme activities of the HECT family E3 ligases.Nature Communications10, 3162.

3. Shan Z, Tu Y, Yang Y, Liu Z, Zeng M, Xu H, Long J, Zhang M, Cai Y*, Wen W*. (2018) Basal condensation of Numb and Pon complex via phase transition during Drosophila neuroblast asymmetric division. Nature Communications9, 737.

4. Yao W, Shan Z, Gu A, Fu M, Shi Z, Wen W*. (2018) WW domain-mediated regulation and activation of E3 ubiquitin ligase Suppressor of Deltex. Journal of Biological Chemistry293, 16697-16708.

5. Chen X, Liu Z, Shan Z, Yao W, Gu A, Wen W*. (2018) Structural determinants controlling 14-3-3 recruitment to the endocytic adaptor Numb and dissociation of the Numb/α-adaptin complex. Journal of Biological Chemistry293, 4149-4158.

6. Zhu K, Shan Z, Chen X, Cai Y, Cui L, Yao W, Wang Z, Shi P, Tian C, Lou J, Xie Y, Wen W*. (2017) Allosteric auto-inhibition and activation of the Nedd4 family E3 ligase Itch. EMBO Report18, 1618-1630.

7. Zhu K, Shan Z, Zhang L, Wen, W*. (2016) Phospho-Pon binding mediated fine-tuning of Plk1 activity.Structure24, 1110-1119.

8. Jia M, Shan Z, Yang Y, Liu C, Li J, Luo ZG, Zhang M, Cai Y*, Wen W*, Wang W*. (2015) The structural basis of Miranda-mediated Staufen localization during Drosophila neuroblast asymmetric division. Nature Communications6, 8381.

9. Pan Z, Shang Y, Jia M, Zhang L, Xia C, Zhang M, Wang W*, Wen W*. (2013) Structural and biochemical characterization of the interaction between LGN and Frmpd1. Journal of Molecular Biology425, 1039-1049.

10. Zhu J, Shang Y, Xia C, Wang W, Wen W*, Zhang M*. (2011) Guanylate Kinase Domains of the MAGUK Family Scaffold Proteins as Specific Phospho-protein-binding Modules EMBO Journal30, 4986-4997.

11. Liu W#, Wen W#, Wei Z, Yu J, Ye F, Liu CH, Hardie RC, Zhang M*. (2011) The INAD scaffold is a dynamic, redox-regulated modulator of signaling in the Drosophila eye. Cell145, 1088-1101. (#: co-first authors) (Cover article)

Highlights: F1000,http://f1000.com/prime/12082956

12. Zhu J#, Wen W#, Zheng Z, Shang Y, Wei Z, Xiao Z, Pan Z, Du Q, Wang W*, Zhang M*. (2011) LGN/mInsc and LGN/NuMA complex structures suggest distinct functions in asymmetric cell division for the Par3/mInsc/LGN and Gαi/LGN/NuMA pathways. Molecular Cell43, 418-431. (#: co-first authors)  

13. Wen W, Yu J, Pan L, Wei Z, Weng J, Wang W, Ong YS, Hoai TTT, Hong W, Zhang M*. (2010) Lipid-induced conformational switch controls fusion activity of longin domain SNARE Ykt6. Molecular Cell37, 383-395.

Highlights: F1000, http://f1000.com/prime/2939958