The University of Texas Health Science Center at Houston
麦戈文医学院
Institute of Molecular Medicine

With an unprecedented longer life expectancy, our society is facing a pressing challenge from aging-related neurodegenerative disorders (NDs) such as Alzheimer’s (AD), Parkinson’s (PD) and Huntington’s (HD) diseases. To understand the pathogeneses of these devastating brain disorders, we need to address two essential questions: (1) What are the normal functions of disease-causative genes? (2) How are the formation of protein aggregates, a common pathological hallmark of NDs, regulated? Our laboratory employs Drosophila, commonly known as the fruit fly, which is one of the best-studied model organisms, to address these questions, with focus on the following areas:

I.Dissecting the endogenous function of the Huntington’s disease gene Huntingtin: HD is caused by an abnormal expansion of a polyglutamine tract in the Huntingtin (Htt) protein, and disruption of its normal functions has been implicated in the disease pathogenesis. To elucidate its still mysterious endogenous functions, we have knocked out the gene in the fruit fly that is homologous to human Htt and found that this Drosophila Htt (dhtt) affects the mobility and long-term survival of adult animals as well as axonal terminal complexity in the brain. We are currently taking advantage of the abundant experimental tools available in Drosophila to dissect out the normal function of this enigmatic protein.

II.研究细胞内蛋白质聚集体的形成: Formation of protein aggregates is believed to be a dynamic process involving multiple intermediate species of different sizes and conformations (e.g., oligomers, proto- and pre-fibrils, fibrils), and their effects on neuronal degeneration may vary from toxic to protective. Thus, understanding their regulation will be important in finding effective treatments for these diseases. We have established a cell-based quantitative high-throughput assay that allows automated measurement of aggregates within Drosophila cells and have further carried out a genome-wide RNA interference (RNAi) screen on mutant Htt protein, from which we identified a diverse group of regulators that affected aggregates formation. Using this established high-throughput assay and the isolated regulators as entry points, we are systematically studying the molecular networks regulating aggregates formation and neuronal toxicity.

III. Analyzing the intracellular handling of neurotransmitter dopamine in dopaminergic neurons：PD的特征是大脑中多巴胺能（DA）神经元的进行性丧失。为了促进使用苍蝇研究PD的研究，我们正在开发体内测定法，以分析果蝇组织中多巴胺的细胞内处理。

我们实验室中的教程将使学生了解人类ND的致病机制的多学科方法，包括神经科学分析，高分辨率成像，全基因组范围的测定法，以及传统的细胞生物学，生物化学和许多基因操纵工具古典果蝇模型系统。

Imm师

教育和培训

Ph.D. - Yale University - 2001

Research Opportunities

• Seeking PhD Students

程式

• 遗传学and Epigenetics
• 神经科学