Research Interests

Dr. Zhiping Wang is an awardee of the National Thousand Young Talent program. The Wang lab focuses on two research 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) searching for PQC regulators affecting axon regeneration post injury, and screening for small compounds that promote axon regrowth via regulating 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. Currently the lab is funded by NSFC, the National Thousand Talents Plan, and the National Key R&D Plan.

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 are investigating how PQC is accordingly regulated under physiological and pathological processes in live organisms. In the long run, we want to identify new PQC regulators that guard the accuracy of neurodevelopment and explore solutions to developmental PQC diseases.

Another question we are investigating 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.