Dr. Lee, Hsiu-Hsiang's Laboratory

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國立臺灣大學醫學院
分子醫學研究所
李秀香老師實驗室
Ph.D. Lee, Hsiu-Hsiang.

Institute of Molecular Medicine, School of Medicine, National Taiwan University, 7 Chung Shan South Rd., Taipei, Taiwan, R.O.C.

Tel: 886-2-23123456 ext.88365 (office)  88366(lab)
Fax: 886-2-23221675

Email: hsiuhsianglee@ntu.edu.tw

Last Update: 2012/12

 
 

Research Interest

I am working to uncover the mechanisms by which the nervous system remodels its neuronal connectivity during development. The precise wiring of neuronal circuitry is essential for the proper function of nervous system. However, the initial configuration of developing nervous system begins as an approximate prototype, further remodeling is often required to achieve the mature connectivity. Pruning is a tightly controlled self-destructive process that selectively eliminates specific parts of neuronal processes without causing cell death. Neuronal pruning is not only a widely observed mechanism in developing nervous system to ensure precise wiring, but also renders the nervous system to adjust neuronal connectivity in response to injury or diseases. However, little is known about the cellular and molecular basis of neuronal injury and diseases. Given the similarity between the developmentally programmed neuronal pruning and the pruning that ensues neuronal injury and diseases, the machinery that executes the elimination of neuronal processes is likely shared in all three circumstances. I plan to use the nervous system of Drosophila (fruit fly) as a model system to dissect the molecular mechanisms of neuronal pruning by various approaches, including biochemical, molecular and cellular biology and the powerful genetics of Drosophila.

In Drosophila, extensive neuronal remodeling takes place during metamorphosis to reorganize the larval nervous system into adult patterns. Some class IV dendritic arborization (da) neurons, a subset of larval peripheral sensory neurons, undergo a large-scale dendrite pruning to eliminate all their larval dendrites prior to the regeneration of adult dendrites, yet leave their axons intact. Dendrite pruning of class IV da neurons begins with severing the proximal dendrites, followed by removal all the remnants of severed dendrite by phagocytes. While some molecules required for dendrite pruning begin to be discovered, little is known about the molecular mechanisms for dendrite severing. During my postdoctoral study, I identified Ik2 kinase, a Drosophila IKK-related kinase, and katanin p60-like 1 (kat-60L1), a novel microtubule-severing molecule, and have shown that both genes are essential to initiate dendrite severing in Drosophila peripheral neurons during metamorphosis.

In the near future, I intend to study the molecular mechanisms of dendrite severing in the fly nervous system through following directions:

  1. Functional analysis of Ik2 kinase and its interacting proteins in dendrite pruning.
  2. Characterization of the function and regulation of Kat-60L1 in dendrite severing
  3. Elucidation of mechanisms that confine the pruning activity to subcellular compartments in neurons.
     
 

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