We focus on using chemical intervention to control the neuronal gene expression in human. Adult neurons cannot repair themselves upon damage. Patients suffer devastating results from neurodegenerative diseases such as Alzheimer's, while adult neuronal stem cells remain dormant in human body. If we can identify chemical agents to re-activate the neuronal stem cells and promote the differentiation of neuronal stem cells, it will greatly improve the health and life quality of millions of people. We study a family of human phosphatases whose inhibition leads to neuronal regeneration. Using structural biology, we sketch out the road map for the targeting protein and optimize the properties of these compounds rationally. Specially, we will optimize our initial lead for higher potency and better accuracy so that eventually we can develop this series of compounds as therapeutic agents to facilitate neuronal differentiation to repair nervous system damage. Such chemical compounds will be valuable tools for scientists studying neuronal development to rationally control the process.