Hsiu-Hsiang Lee Ph.D.
Basic Medicine Building 1516
Tel：Tel: 886-2-23123456 ext.288365 (office) 288366(lab)
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:
- Functional analysis of Ik2 kinase and its interacting proteins in dendrite pruning.
- Characterization of the function and regulation of Kat-60L1 in dendrite severing
- Elucidation of mechanisms that confine the pruning activity to subcellular compartments in neurons.
- 1992 B.S. Biochemistry
Department of Agricultural Chemistry, National Taiwan University, Taiwan
- 1994 M.S. Immunology
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taiwan
- 2003 Ph.D. Developmental Biology
Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine of New York University, USA
- 2009-present Assistant Professor, Graduate Institute of Molecular Medicine, School of Medicine, National Taiwan University, Taiwan
- 2004-2009 Postdoctoral fellow, University of California, San Francisco, CA, USA
- 2003-2004 Postdoctoral fellow, Mount Sinai School of Medicine, New York, NY, USA
- 賴玉婷: 1st year Master Course, (2011 admission)
- 潘柏元: 2nd year Master Course, (2010 admission)
- Lee, HH.*, Ho, HY.* and Lai, MZ. (1997). Overexpression of mitogen-activated protein kinase kinase kinase reversed cAMP inhibition of NF-kappaB in T cells. Eur J Immunol. 27, 222-226. (* equal contribution).
- Hsu, SC., Gavrilin, MA., Lee, HH., Wu, CC., Han, SH. and Lai, MZ. (1999). NF-kappa B-dependent Fas ligand expression. Eur J Immunol. 29, 2948-2956.
- Xiong, JW., Leahy, A., Lee, HH. and Stuhlmann, H. (1999). Vezf1: A Zn finger transcription factor restricted to endothelial cells and their precursors. Dev Biol. 206, 123-141.
- Lee, HH. and Frasch, M. (2000). Wingless effects mesoderm patterning and ectoderm segmentation events via induction of its downstream target sloppy paired. Development 127, 5497-5508.
- Zaffran, S., Kuchler, A., Lee, HH. and Frasch, M. (2001). biniou (FoxF), a central component in a regulatory network controlling visceral mesoderm development and midgut morphogenesis in Drosophila. Genes & Dev. 15, 2900-2915.
- Weiss, JB., Suyama, KL., Lee, HH. and Scott, MP. (2001). Jelly belly: a Drosophila LDL receptor repeat-containing signal required for mesoderm migration and differentiation. Cell 107, 387-398.
- Zaffran, S., Xu, X., Lo, P., Lee, HH. and Frasch, M. (2002). Cardiogenesis in the Drosophila model: control mechanisms during early induction and diversification of cardiac progenitors. Cold Spring Harb Symp Quant Biol. 67, 1-12.
- Reim, I., Lee, HH. and Frasch, M. (2003). The T-box-encoding Dorsocross genes function in amnioserosa development and the patterning of the dorsolateral germ band downstream of Dpp. Development 130, 3187-3204.
- Lee, HH., Norris, A., Weiss, JB. and Frasch, M. (2003). Jelly belly protein activates the receptor tyrosine kinase Alk to specify visceral muscle pioneers. Nature 425, 507-512.
- Lee, HH. and Frasch, M. (2004). Survey of forkhead domain encoding genes in the Drosophila genome: Classification and embryonic expression patterns. Dev Dyn. 229, 357-366.
- Lee, HH. and Frasch, M. (2005). Nuclear integration of positive Dpp signals, antagonistic Wg inputs and mesodermal competence factors during Drosophila visceral mesoderm induction. Development 132,1429-1442.
- Lee, HH., Zaffran, S. and Frasch, M. (2006). Development of the Larval Visceral Musculature. In Muscle Development in Drosophila, ed. H. Sink, pp. 62-78. New York: Springer. (Book chapter).
- O'Reilly, AM., Lee, HH., and Simon, AM. (2008). Integrins control the positioning and proliferation of follicle stem cells in the Drosophila ovary. J Cell Biol. 182, 801-815.
- Lee, HH., Jan, LY., Jan, YN (2009). Drosophila IKK-related kinase Ik2 and Katanin p60-like 1 regulate dendrite pruning of sensory neuron during metamorphosis. Proc Natl Acad Sci U S A. 106, 6363-6368.
- Lin T., Pan PY., Lai YT., Chiang KW., Hsieh HL., Wu YP., Ke JM., Tang CY., Yang SB., Cheng HC., Wu JT., Jan YN. and Lee, HH. (2015) Spindle-F is the central mediator of Ik2 kinase-dependent dendrite pruning in Drosophila sensory neurons. PLoS Genetics 11(11): e1005642.