Xiang Gao, PhD

Bio

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.

Titles & Appointments

Assistant Research Professor of Neurological Surgery

Education

2000 PhD Shanghai Institute of Biochemistry and Cell Biology

1992 BS Nanjing University
Research

Traumatic brain injury (TBI) is an increasingly public health and medical problem. An estimated 2.5 million cases occur within the USA each year, which contribute to a substantial number of deaths and cases of permanent disability. The impact on a person and his or her family can be devastating. To date, there is no effective treatment for this disease yet.

The brunt of my research as a post-doctorate has been in the traumatic brain injury field, specifically focusing upon neural protection, neural degeneration, glia response, and regeneration. The continuing focus of my research is twofold: to find an effective way to mitigate, or even prevent, cell death and degeneration post traumatic brain injury (TBI) and to explore the potential of stem cells for repairing damaged neocortical circuitry.

       Preventing the cell death, in another word, stop or block the damage from beginning is always the most effective way against the TBI. To achieve it, we should first understand the underlying mechanisms of cell death causing by TBI. The neuronal excitotoxicity caused by robust increase of glutamate after TBI is my mainly interested area. NMDA receptor sub-unit 2 B (NR2B) mediated signal pathway had been proven played critical role in neuronal excitotoxicity after TBI and its blockage resulted in lessening of cell death. However, how does this signal pathway work is still unclear. Study on this signal pathway will augment our understanding of cell death after TBI.

        No limit to the cell death, dendrites are very vulnerable to the insult. My findings demonstrated the dramatic dendrite structural changes, such as swelling, branch loss and spine reduction, happened even in mildly injured mice without obvious cell death. Live imaging using thinning-skull technique and combined with 2-photon confocal microscopy further revealed dendrite and spine degeneration and plasticity in vivo. The correlation of dendrite and spine degeneration and functional loss suggested dendrite and spine degeneration may have a large contribution to the neural disorders after TBI. There is an advantage of preventing dendrite degeneration. Comparing to the cell death, the preventing of dendrite and spine degeneration had much wider and longer time window from hours to weeks. This gives us a real opportunity, especially in clinic field to practically prevent it. However, the mechanism of dendrite degeneration is not well known and need to be revealed. Calpain mediated cytoskeleton degradation was suggested playing the critical role in inducing the dendrite degeneration in spared neurons by disrupting the cell cytoskeleton. My further study will focus on it. Meanwhile, stabilizing the cytoskeleton such as microtubules by drug may help cell against dendrite degeneration.

     Seeking a non-transplantation method for repairing the cortical cavity caused by cell death, we designed to create 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 therapeutic application for curing TBI.

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