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My research focuses on the mechanisms by which dopaminergic neurons selectively degenerate in Parkinson's disease (PD). PD primarily results from a substantial and progressive loss of dopaminergic neurons in the midbrain. At present, the neurons at risk cannot be protected and the disease progression cannot be prevented by any treatments available because we have a very limited understanding on the disease mechanisms. Recent advance in genetic and epidemiological study suggests a multifactorial etiology for PD. As a multifactorial disease, PD may be caused by harmful interaction between environmental toxins and genetic factors during the aging process. We have created genetically mutated animals that overexpress the disease-linked genes or are depleted of neuroprotective genes. With these genetic models, we are studying how dopaminergic neurons degenerate in the presence and in the absence of environmental toxicants.
Our laboratory uses multidisciplinary approaches to study the disease mechanisms. In collaboration with the transgenic core directed by Dr. Carlisle Landel, we have developed a technique to produce transgenic rats by pronuclear injection. Traditional gene knockout, transgenic RNAi knockdown, and transgenic gene overexpression are routinely used to produce transgenic animals in our lab. To analyze the animal models, we use histological (fluorescence and electron microscopy), biochemical (proteomics), molecular (Southern and Northern blotting, and DNA and miRNA microarray), and electrochemical (in vivo microdialysis coupled with HPLC, and cyclic voltammetry) approaches.
By a better understanding on the disease mechanisms, the pace to find a cure for PD would be accelerated.
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