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側邊選單開關 研究人員
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  • Tzu-Yang Lin大頭照
    Tzu-Yang Lin Tzu-Yang Lin老師 Research ID Tzu-Yang Lin老師 ORCID
    Associate Research Scientist
    • 專長：Genetics, Neurobiology, Disease models
    • 信箱：tzuyanglin@gate.sinica.edu.tw
    • 電話：02-2787-1533
    • 網站： Laboratory of Neurobiology
    • 位置：R536/ICOB
友善列印
經歷簡介展開收合
2018-
Assistant Research Scientist of ICOB, Academia Sinica
2014-
Assistant Professor, Graduate Institute of Life Sciences, National Defense Medical Center, Taiwan
2009-2014
Postdoctoral Fellow, NICHD/NIH, USA
2004-2008
Postdoctoral Fellow, NHRI, Taiwan
2004
Ph.D., Molecular Biology, National Tsing Hua University, Taiwan
研究方向展開收合

Dissect Gliomagenesis by an Adult Drosophila Model System

Glioblastoma multiforme (GBM), has the most common and highest mortality rate among primary brain tumors in adults. It remains the most aggressive brain tumor with no cure due to its invasive nature, heterogeneity, and complex pathological mechanisms. Frequent genetic alterations that activate epidermal growth factor receptor (EGFR) and phosphatidylinositol-3 kinase (PI3K) signaling, as well as metabolic remodeling, have been associated with gliomagenesis. 

Modeling human GBM in Drosophila has recently become feasible by introducing glioma driver mutations specifically in glia cells. Fly glioma model recapitulates many key features of human GBM with regard to increased cancer cell proliferation, migration, invasiveness, and tumor stiffening. Numerous gliomagenic pathways, such as the receptor tyrosine kinase (RTK) signaling and metabolic pathways, are highly conserved from fruit fly to human. These features make Drosophila a valid and attractive system that can be used to elucidate mechanisms of gliomagenesis, perform genetic screenings and eventually be beneficial for developing future therapeutics. 

We have established an adult fly glioma model (Chi et al., 2019) utilizing genetic gain and mutational activation of the EGFR and PI3K pathways (is found in over 40% of GBMs). In this system, glioma-induced animals showed significant brain enlargement, locomotor abnormalities, memory deficits, and a shorter lifespan. Combining systematic analysis using genetic, pharmacologic, and cell biology approaches, this in vivo model could allow the determination of the pathometabolic pathways involved in gliomagenesis, as well as provide valuable mechanismic insight for novel therapeutic strategies. 

代表著作展開收合
  1. Lin, T. Y., Chen, P.J., Yu, H. H., Hsu, C. P., and Lee, C. H.  (2021) Extrinsic Factors Regulating Dendritic Patterning. Front Cell Neurosci. Jan 13;14:622808. 
  2. Li, Y., Chen, P.-J., Lin, T.-Y., Ting, C.-Y., Muthuirulan, P., Pursley, R., Ilić, M., Pirih, P., Drews, M., Menon, K. P., Zinn, K. G., Pohida, T., Borst, A., and Lee, C.-H.  (2021) Neural Mechanism of Spatio-chromatic Opponency in the Drosophila Amacrine Neurons. Curr Biol. Jul 26;31(14):3040-3052.e9 
  3. Luo, J., Ting, C.-Y., Li, Y., McQueen, P. G., Lin, T. Y., Hsu, C. P., and Lee, C. H.  (2020) Antagonistic Regulation by Insulin-like Peptide and Activin Ensures the Elaboration of Appropriate Dendritic Field Sizes of Amacrine Neurons. eLife 2020:9:e50568. 
  4. Chi, K. C., Tsai, W. C., Wu, C. L., Lin, T. Y.*, and Hueng, D. Y.*  (2019) An Adult Drosophila Glioma Model for Studying Pathometabolic Pathways of Gliomagenesis. Molecular Neurobiology, 56(6), 4589-4599. (* Corresponding Author) 
  5. Lin, T. Y., Luo, J., Shinomiya, K., Ting, C. Y., Lu, Z., Meinertzhagen, I.A., and Lee, C. H.  (2016) Mapping Chromatic Pathways in the Drosophila Visual System. Journal of Comparative Neurology, 524(2), 213-227. (Featured cover image) 
  6. Macpherson, L.J., Zaharieva, E.E., Kearney, P.J., Alpert, M.H., Lin, T. Y., Turan, Z., Lee, C. H., and Gallio, M.  (2015) Dynamic, Multi-color Labeling of Neural Connections by Trans-synaptic Fluorescence Complementation. Nature Communications, 6, Article number: 10024. 
  7. Karuppudurai, T.*, Lin, T. Y.*, Ting, C. Y., Pursley, R., Melnattur, K.V., Diao, F., White, B.H., Macpherson, L.J., Gallio, M., Pohida, T., and Lee, C. H.  (2014) A Hard-wired Glutamatergic Circuit Pools and Relays UV Signals to Mediate Spectral Preference in Drosophila. Neuron, 81, 603-615. (*co-first author)  (Recommended in F1000Prime) 
  8. Lin, T. Y.*, Huang, C. H.*, Kao, H. H., Liou, G. G., Yeh, S. R., Cheng, C. M., Chen, M. H., Pan, R. L., and Juang, J. L. (2009) Abi plays an opposing role to Abl in Drosophila axonogenesis and synaptogenesis. Development, 136 (18), 3099-3107. (*co-first author)