My interest in neuroscience derived from years of scientific training. As a Ph. D. student, I studied the underlying molecular mechanism in neuronal fate decision. I have developed many basic skills for scientific research during this period which could help me initiate a new project smoothly, even facing a comparable new field.
During my postdoctoral training, I started to work in the traumatic brain injury field. I focused on neural protection, neural degeneration, glia response, and regeneration. First, I characterized cell death in the hippocampus following TBI using controlled cortical impact model and found that the immature neuron is the most vulnerable cell type when subjected to insult. I further demonstrated injured mice could have a spontaneous and precise response to the cell loss. Neural stem cells located in the subgranular zone will have a transient and significantly increased proliferation, which could generate more neurons to compensate for the loss. Meanwhile, I first found there were extensive dendrite and spine degeneration within the spared neurons in the hippocampus after TBI. Dendrites are very sensitive to insult. The dramatic dendrite structural changes, such as swelling, branch loss and spine reduction, could be found even in the mildly injured mice without obvious cell death. Glial response is another important aspect related to brain injury. I worked alongside others in our lab to characterize astrocyte and microglia pathological changes after moderate TBI. Moreover, we found increasing mTOR signal pathway activity is necessary for the proliferation of reactive glia. I further proved PDGF can regulate the reactive astrocyte proliferation through PDGFR mediated signal pathway to revoke mTOR activity after TBI. Seeking a non-transplantation method for repairing the cortical cavity caused by cell death, I innovatively created a stem cell niche in the cortex using the iPS method in vivo. The stem cells could be affected by their local environment to generate sufficient neurons to fill the cavity in the injured cortex. This method may create a potentially large therapeutic application for curing TBI.
As a junior investigator, I attract, train, and mentor undergraduate and graduate students in neuroscience research. All of them were awarded intramural and extramural scholarships, and their research has produced peer-reviewed publications.