羅椀升

羅椀升
Lo, Wan-Sheng
副研究員

Ph.D. Biology, St. John’s University, New York

TEL: 

+886 2 2787-1163 (Office)
+886 2 2787-1039 (Lab)

研究領域:

本實驗室的研究重點在於了解細胞生長分化的過程中,染色質結構變化之原因及其對基因調控之作用。我們利用酵母菌及阿拉伯芥作為實驗的材料,探討表觀遺傳學及基因調控分子機制。研究主題有二:

一 、組蛋白修飾對染色質結構、基因表達及基因組穩定性之調控機制

染色質是由DNA纏繞組蛋白(H2A 、H2B 、H3 、H4)形成之核小體所構成,而染色質修飾(chromatin modifications)在基因轉錄調控中扮演重要的角色。目前,我們致力於探討去甲基酶複合體活性及組蛋白修飾的改變對於活化基因之影響及其調控機制。利用基因體學及蛋白質體學分析,我們發現H3K36 去甲基酶(Rph1)可直接結合染色質並抑制基因轉錄。藉由調控Rph1 的磷酸化和蛋白質表現量以控制其與染色質結合,調節標的基因表達,適切反應不同環境所需的生理功能,以達到細胞正常生長的平衡。而H3K4 去甲基酶(Jhd2)在基因轉錄靜默區域的異染色質有較高的結合力,並具有阻絕不同區域染色質及修飾特定染色質結構的活性,以達到調控異染色質之基因靜默。此外,我們發現表觀遺傳特性之改變會影響植物非整倍體之基因組穩定性,以及非編碼RNA的表現參與菌絲生長的調控。目前針對細胞老化之調控機制進行深入研究,以期了解表觀遺傳及基因轉錄如何調節細胞適應環境壓力的分子機制。(圖ㄧ)

二、研究真菌菌絲發育及篩選抗菌之新穎化合物

研究真菌致病機制及開發抗菌新標靶藥物,為防治黴菌感染之重要課題。利用實驗室以酵母菌建立的藥物篩選平台,我們已篩選得到多種抑制假性菌絲形成的小分子化合物。目前以分子遺傳學技術、化學遺傳學、蛋白質體學及基因晶片等方法,進行小分子化合物抑菌機制之研究。預期本研究之成果可增進對真菌致病及抗藥機制的了解,亦有助於研發植物保護製劑及治療人類與動物真菌感染之藥物。(圖二)

All publication list

 

Selected publication list

 

  • Wang LC, Montalvo-Munoz F, Tsai YC, Liang CY, Chang CC, Lo WS*. (2015) The histone acetyltransferase, Gcn5, regulates ncRNA-ICR1 and FLO11 expression for pseudohyphal development in yeast Saccharomyces cerevisiae. BioMed Research International doi:10.1155/2015/284692

  • Catinot J, Huang JB, Huang PY, Tseng MY, Chen YL, Gu SY, Lo WS, Wang LC, Chen YR, Zimmerli L*. (2015) ETHYLENE RESPONSE FACTOR 96 positively regulates Arabidopsis resistance to necrotrophic pathogens by direct binding to GCC elements of jasmonate - and ethylene-responsive defence genes. Plant, Cell and Environment doi:10.1111/pce.12583

  • Lo KL, Wang LC, Chen IJ, Liu YC, Chung MC and Lo WS* (2014) Transcriptional consequence and impaired gametogenesis with high-grade aneuploidy in Arabidopsis thaliana. PLoS One, doi:10.1371/journal.pone.0114617.

  • Liang CY, Wang LC, Lo WS * (2013) Dissociation of the H3K36 demethylase Rph1 from chromatin mediates derepression of environmental stress-response genes under genotoxic stress in Saccharomyces cerevisiae. Molecular Biology of the Cell 24(20):3251-3262.

  • Chen IJ, Lo WS, Chuang JY, Cheuh CM, Fan YS, Lin YC, Wu SJ, Wang LC* (2013) Chemical genetics reveals a role of brassinolides and cellulose synthase in the hypocotyl development of etiolated Arabidopsis seedlings. Plant Science 209: 46-57.

  • Liang CY, Hsu PH, Chou DF, Pan CY, Wang LC, Huang WC, Tsai MD, Lo WS * (2011) The histone H3K36 demethylase Rph1/KDM4 regulates the expression of the photoreactivation gene PHR1. Nucleic Acids Research. 39(10): 4151-4165.

  • Tu S, E. Bulloch MM, Yang L, Ren C, Huang WC, Hsu PH., CH Chen CH, Liao CL, Yu HM, Lo WS *, Freitas MA*, Tsai MD* (2007) Identification of histone demethylases in Sacchromyces cerevisiae.   J. Biol. Chem. 282(19): 14262-71

  • Nayak V, Zhao K, Wyce A, Schwartz MF, Lo WS, Berger SL, Marmorstein R*  (2006) Structure and dimerization of the kinase domain from yeast Snf1, a member of the Snf1/AMPK protein family. Structure 14(3): 477-485.

  • Lo WS, Gamache ER, Harry KW, Yang D, Pillus L and Berger SL* (2005) Activator-targeted Snf1-mediated histone H3 phosphorylation promotes TBP recruitment through distinct promoter-specific mechanisms. EMBO J. 24:997-1008

  • Lo WS, Henry KW, Schwartz MF and Berger SL* (2004) Histone modification patterns during gene activation. Method in Enzymology 377:130-153

  • Clements A, Poux AN, Lo WS, Pillus L, Berger SL, and Marmorstein R* (2003) Structural basis for histone and phospho-histone binding by the GCN5 histone acetyltransferase. Molecular Cell, 12(2):461-473

  • Henry KW, Wyce A, Lo WS, Duggan LJ, Emre NCT, Kao CF, Pillus L, Osley MA and Berger SL*  (2003) H2B ubiquitylation and deubiquitylation through the SAGA-associated hydrolase Ubp8 are both required for transcriptional activation. Gene & Dev., 17(21):2648-2663

  • Lo WS, Duggan LJ, Belotserkovskya R, Emre NCT, Lane W, Shiekhattar R, and Berger SL* (2001) Snf1 is a histone kinase which works in concert with the histone acetyltransferase Gcn5 to regulate transcription. Science, 293:1142-1146.

  • Lo WS, Trievel RC, Rojas JR, Duggan L, Hsu JY, Allis CD, Marmorstein R and Berger SL* (2000)  Phosphorylation of Serine 10 in Histone H3 Is Functionally Linked In Vitro and In Vivo to Gcn5-Mediated Acetylation at Lysine 14. Molecular Cell 5(6): 917-926.

博士班學生 Ph.D. student

Md. Torikul Islam, 托路可

Shin-Yuan Gu, 顧心元

Wei-Han Lin, 林暐瀚

碩士班學生 Master student

Fang-Ching Chuang, 莊芳晴

研究助理 Research Assistant

Chiao-Mei Chueh, 闕巧梅

Shao-Chang Huang, 黃紹昌

Tsiao-Ting Yan, 殷筱婷