Profile

Education and Research Experience2008-2015 University of California-San Diego, USA          Post-Doctoral Fellow/Assistant Project Scientist2008 Duke University, USA     Ph.D., Neurobiology                            2001 Tsinghua Unviersity, China     B.S., Biological Sciences and Biotechnology Research InterestsWe are interested in two directions: (1) studying the mechanisms of protein quality control (PQC) in neuronal development and circuit formation, and elucidating their clinical relevance to certain PQC diseases; (2) studying the mechanisms of axon regeneration, and screening for small compounds that promote axon regrowth through enhancing PQC. C. elegans and mouse, two powerful model organisms, are used in our lab for discovering conserved PQC mechanisms involved in these essential neurobiological processes. In healthy cells, aberrant proteins caused by biosynthetic errors, environmental variations and background mutations are tightly restricted to a harmless level by protein quality control (PQC). The PQC system consists of two parts, molecular chaperones and protein degradation systems (proteasome, autophagy and AAA+ proteases), and is essential for the health of all cells. Although generally being considered as a “house-keeping” process, the PQC network vary greatly among different tissues and brain regions. Besides, the overall robustness of neuronal PQC declines during aging so that adult neurons are susceptible to environmental stress and genetic mutations.  Currently, we know little about how PQC is accordingly regulated under physiological and pathological processes in live organisms. Our previous discovery of an evolutionarily conserved PQC regulator EBAX-1 (Elongin BC-Binding AXon Regulator-1), which participates in degradation of misfolded proteins, demonstrated the importance of PQC during neuronal development and laid the foundation for our current research. We are investigating if similar PQC mechanism are used in vertebrates. In the long run, we want to identify more new PQC regulators that guard the accuracy of neuronal circuit formation and explore solutions to developmental PQC diseases. The second direction we focus on is molecular mechanisms of axon regeneration. Nerve injuries can cause dramatic disruption of the cellular environment and accumulation of stress-triggered cellular hazards, which need to be removed by PQC. The functional regeneration of injured axons also heavily relies on the PQC network for overcoming barriers of regrowth and rebuilding connections. However, how PQC participate and contribute to these processes remains unclear. Currently, we are systematically examining the influence of PQC regulators, including molecular chaperones and protein degradation machinery, on axon regeneration. The PQC mechanisms in juvenile and adult neurons after injury will be compared to identify stage-specific PQC components. We are also keen to identify small compounds that can promote axon regrowth through PQC by performing high-throughput drug screening in C. elegans. Discovering new PQC genes and drugs will improve our current understanding of PQC in live organisms and inspire novel therapeutic interventions for common neurodevelopmental and neurodegenerative diseases. Publications1. Xing Guo, Xiaorong Wang, Zhiping Wang, Sourav Banerjee, Jing Yang, Lan Huang and Jack E. Dixon. (2015) Site-specific proteasome phosphorylation controls cell proliferation and tumorigenesis. Nature Cell Biology 18, 202–2122. Zhiping Wang, Yanli Hou, Xing Guo, Monique van der Voet, Mike Boxem, Jack E. Dixon, Andrew D. Chisholm, and Yishi Jin. (2013) The EBAX-type Cullin-RING E3 ligase and Hsp90 guard the protein quality of the SAX-3/Robo receptor in developing neurons. Neuron 79, 903-16.3. Lizhen Chen, Zhiping Wang, Anindya Ghosh-Roy, Thomas Hubert, Dong Yan, Sean O'Rourke, Bruce Bowerman, Zilu Wu, Yishi Jin, Andrew D Chisholm. (2011) Axon Regeneration Pathways Identified by Systematic Genetic Screening in C. elegans. Neuron 71, 1043-57.  4. Zhiping Wang*, Yishi Jin*. (2011) Genetic dissection of axon regeneration. Current Opinion in Neurobiology 21, 189-96. 5. Sharon Sann, Zhiping Wang, Heather Brown, Yishi Jin. (2009) Roles of endosomal trafficking in neurite outgrowth and guidance. Trends in Cell Biology 19, 317-24. 6. Zhiping Wang, Jeffrey G. Edwards, Nathan Riley, D. William Provance, Jr., Ryan Karcher, John A. Mercer, Julie A. Kauer, Xiang-Dong Li, Ian G. Davison, Mitsuo Ikebe, and Michael D. Ehlers. (2008) Myosin Vb Mobilizes Recycling Endosomes and AMPA Receptors for Postsynaptic Plasticity. Cell 135, 535-548. 7. Xing Guo, David S. Waddell, Wei Wang, Zhiping Wang, Nicole T. Liberati, Sheila Yong, Xuedong Liu, and Xiao-Fan Wang. (2008) Ligand-dependent ubiquitination of Smad3 is regulated by casein kinase 1 gamma 2, an inhibitor of TGF-beta signaling. Oncogene 23, 7235-7247. 8. Chang Zhou, Zhexing Wen, Zhiping Wang, Xing Guo, Dongmei Shi, and Zuoping Xie. (2003). Green fluorescent protein-labeled mapping of neural stem cells migrating towards damaged areas in the adult central nervous system. Cell Biology International 27, 943-945.