| Biography | |
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 Prof. Xiao-Jiang Li Emory University School of Medicine, China |
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| Title: Genetically modified monkey models of neurological disorders | |
| Abstract:
Genetically modified animal models have been extensively used to investigate the pathogenesis of age-dependent neurodegenerative diseases, such as Alzheimer (AD), Parkinson (PD), Huntington (HD) diseases, and Amyotrophic lateral sclerosis (ALS). The common feature of these diseases is the age-dependent accumulation of misfolded proteins in the brain, which can be recapitulated in a variety of mouse models of neurodegenerative diseases. However, the brains of transgenic mouse models of AD, PD, and HD do not show the striking neuronal loss or degeneration that is a typical pathological feature in patient brains. Species differences between small animals and humans may account for differential pathology in transgenic mouse models and patient brains. We have used transgenic approaches and CRSPR/Cas9 gene targeting to generate non-human primate models of human diseases. Comparison of transgenic rodent and monkey models of neurodegenerative diseases revealed that large animals may be more sensitive to misfolded proteins and can mimic neuropathology that is more similar to that in patient brains. These studies suggest that non-human primate models should be considered as complementary models to uncover important pathological changes seen in patient brains.
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| Biography:
Research Interests
The main interest of the Li Lab is to understand the molecular mechanisms of inherited neurodegeneration caused by a CAG repeat expansion in the disease genes. Currently, we focus on Huntington's disease (HD), an autosomal dominant genetic disease that is characterized by massive neuronal loss in selective brain regions and affects about 5/100,000 people in North America. The HD protein, huntingtin, forms aggregates in neurons, abnormally interacts with other proteins, and eventually kills neurons. However, it is unclear how mutant huntingtin causes selective neurodegeneration and why the clinical symptoms often occur in mid-life in HD.
To address these important issues, we will use a variety of approaches, including genetic manipulation of animal models, molecular and cell biological analysis of protein transport, and biochemical study of protein-protein interactions, to investigate the relationship between gene mutation and disease phenotypes. Specifically, we are currently investigating the effects of mutant proteins on the function of neurons and glia in the brain, gene transcription, and intracellular trafficking. The goal of our studies is to provide mechanistic insight into the pathogenesis of neurodegeneration caused by polyQ expansion and to help develop effective therapeutic strategies.
Education
MD, Medicine, Jiangxi Medical College, PR China,1977-1982
MS, Pharmacology, Suzhou Medical College, PR China,1983-1986
PhD, Pharmacology, Vollum Institute, The Oregon Health Sciences University, Portland, Oregon,1987-1991
Postdoctoral Research Fellow in Dr. Solomon Snyder's lab in the Department of Neuroscience, Johns Hopkins University School of Medicine, 1991-1995
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