管永恕

姓名：管永恕

職稱：專任副教授

研究室位置：IBS N202

電話：(02)33664063、(02)23665572

Email：yskuan@ntu.edu.tw

研究領域：脊椎動物神經系統發育、神經系統藥物篩選

期刊論文

期刊論文
學經歷
研究方向

年度	論文名稱
2021	Guo-Tzau Wang, He-Yen Pan, Wei-Han Lang, Yuan-Ding Yu, Chang-Huain Hsieh, Yung-Shu Kuan.(2021).Three-dimensional multi-gene expression maps reveal cell fate changes associated with laterality reversal of zebrafish habenula. Wiley. DOI：10.1002/jnr.24806.
2021	Shuxian Lu1#, Zhaojie Lyu1#, Zhihao Wang1, Yao Kou1, Cong Liu1, Shengyue Li1, Mengyan Hu1, Hongjie Zhu1, Wenxing Wang1, Ce Zhang3, Yung-Shu Kuan4, Yi-Wen Liu5, Jianming Chen2,6, Jing Tian1.(2021).Lipin 1 deficiency causes adult-onset myasthenia with motor neuron dysfunction in humans and neuromuscular junction defects in zebrafish. Theranostics 2021 11(6):2788-2805. doi:10.7150/thno.53330.
2015	Kuan, Y.S., Roberson, S., Akitake, C.M., Fortuno, L., Gamse, J.T., Moens, C.B., and Halpern, M.E. (2015). Distinct requirement for Wntless in habenular development. Dev. Biol. (in press)
2015	Wu, B.T., Wen, S.H., Hwang, S.P., Huang, C.J. and Kuan, Y.S.(corresponding author). Control of Wnt5b secretion by Wntless modulates chondrogenic cell proliferation through fine-tuning fgf3 expression. (2015). J. Cell Sci.128:2328-2339.
2014	Lu, C.H., Lin, K.H., Hsu, Y.Y., Tsen, K.T. and Kuan, Y.S. (co-corresponding author). Inhibition of Escherichia coli respiratory enzymes by short visible femtosecond laser irradiation. (2014). J. Phys D-Apply Phys.47(31):315402.
2013	Liao, W.L., Cheng, C.H., Hung, K.S., Chiu, W.T., Chen, G.D., Hwang, P.P., Hwang, S.P.L., Kuan, Y.S. (co-corresponding author), and Huang, C.J. (2013). Protein tyrosine phosphatase receptor type O (Ptpro) regulates cerebellar formation during zebrafish development through modulating Fgf signaling. Cell. Mol. Life Sci. 70:2367-2381.
2010	Kuan, Y.S. , Gamse, J.T., Fortuno, L., Wolf-Saxon, E., Donn, T., Wu, B.T., Moens C.B. and Halpern, M.E. (2010). Zebrafish Wntless mediates habenular neurogenesis. (In preparation)
2009	Kuan, Y.S., Brewer-Jensen, P., Bai, WL., Hunter, C., Wilson, CB., Bass, S., Abernethy, J., Wing, J. S. and Searles, L. L. (2009) Drosophila suppressor of sable protein [Su(s)] promotes degradation of aberrant and transposon-derived RNAs. Mol Cell Biol. 29(20): 5590-5603.
2007	Kuan, Y.S. , Gamse, J.T., Schreiber, A.M. and Halpern, M.E. (2007) Selective asymmetry in a conserved forebrain to midbrain projection. J Exp Zool Mol Dev Evol. 308B(5):669-678.
2007	Kuan, Y.S., Yu, H.H., Moens, C.B. and Halpern, M.E. (2007) Neuropilin asymmetry mediates a left‑right difference in habenular connectivity. Development. 134(5):857-65.
2005	Gamse, J.T., Kuan, Y.S. (co-first author), Macurak, M., Thisse, C., Thisse, B., Brösamle, C., and Halpern, M.E. (2005) Directional asymmetry of the zebrafish epithalamus guides dorsoventral innervation of the midbrain target. Development. 132(21):4869-4881.
2004	Kuan, Y.S., Brewer-Jensen, P. and Searles. L.L. (2004) Suppressor of sable, a Putative RNA-Processing Protein, Functions at the Level of Transcription. Mol Cell Biol. 24(9): 3734-3746.
1996	Lomasney J.W., Cheng H.F., Wang, L.P., Kuan, Y.S., Liu S.M., Fesik S.W. and King K. (1996) Phosphatidylinositol 4,5-Bisphosphate Binding to the Pleckstrin Homology Domain of Phospholipase Cd1 Enhances Enzyme Activity. J. Biol. Chem. 271(41): 25316-25326.
1996	Wang, L.P., Lim C., Kuan, Y.S., Chen C.L., Chen H.F. and King K. (1996) Positive Charge at Position 549 Is Essential for Phosphatidylinositol 4,5-Bisphosphate-hydrolyzing but Not Phospahtidylinositol-hydrolyzing Activities of Human Phospholipase Cd1. J. Biol. Chem. 271(40): 24505-24516.

學校名稱	系所	學位/職稱	期間
中央研究院	生物化學所	合聘副研究員	2018-至今
國立臺灣大學	生化科學所	副教授	2016-至今
中央研究院	生物化學所	合聘助研究員	2009-2018
國立臺灣大學	生化科學所	助理教授	2009-2016
Carnegie Inst. for Science.	Embryology Dept.	Post-doctoral fellow	2003-2008
Academia Sinica.	Inst. of Biomedical Sciences	Research assistant	1994-1996
北卡羅萊納州立大學	生物系	博士	1997-2003
東海大學	生物系	學士	1990-1994

個體發育過程中神經網路是否正確的特化及連結是影響神經系統功能是否正常的關鍵，不正常的神經網路特化及連結會導致病變甚至個體的死亡。利用斑馬魚間腦的habenula nuclei (HA) 及其連結至中腦interpeduncular nucleus (IPN) 之迴路為脊椎動物的模式（圖1），我的研究在探討神經元在胚胎發育過程中如何創生及如何與其他神經元作正確的連結。利用如資料檢視、分子操控及雷射蝕損等方法, 我的結果顯示出有表現Neuropilin 1a (Nrp1a) 的HA神經元其軸突在發育過程中會隨著Semaphorin 3D (Sema3D) 分子的引導而伸入IPN 的背部區塊與其中的神經元產生連結（圖2）。使用化學物誘導突變及原位雜交篩選等實驗策略，我的結果顯示出一個剛發現不久位在Golgi上的蛋白質Wntless (Wls) 是透過控制 neurogenin1 (ngn1) 的表現來影響HA神經元的創生（圖3）。

目前我的研究是進一步的探討在胚胎發育過程中HA神經元的軸突如何正確的長向其目標的機轉, Wls蛋白質如何控制HA神經元創生的機轉, 以及不同特性的HA神經元是如何獲得各自本身獨有的細胞特性。了解控制HA-IPN神經迴路在斑馬魚中發育的機轉將對了解此脊椎動物的腦部結構如何產生有所幫助，進而對了解與神經元創生和連結異常有關的人類病變也將有所幫助。

圖1

圖2

圖3