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專任教師

陳小梨 終身職特聘教授

聯絡電話:02-2312-3456 轉 88378

E-mail: showlic@ntu.edu.tw

個人資料

專長:

1. 利用NRIP基因剔除鼠建立肌肉萎縮及心臟衰節人類疾病模式,藉以了解 NRIP機轉。
2. 利用BCAS2基因剔除鼠建立腦縮小。藉以了解BCAS2和神經及樹突發育的關係。
3. 利用病毒為載体的基因治療。

學歷:

美國約翰霍浦金斯大學哲學博士

經歷:

台大醫學院微生物學科暨研究所教授及所長 (2005.05-2011.07)
國防醫學院微生物暨免疫學研究所教授(1994-2005年9月)
美國約翰霍浦金斯大學病理學系訪問學者(2001/12-2002/05)
國防醫學院微生物暨免疫學研究所副教授(1990/02-1994/08)

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目前進行研究

主要研究方向是

1.         一是NRIP. NRIP為一種AR互動蛋白以及穩定AR蛋白質 (JBC 2005)。此外,NRIP也是男性荷爾蒙調控基因 (NAR, 2008)。另外有趣地發現NRIP是一種鈣離子(Ca+2)依賴性的調鈣素結合蛋白 (JV, 2011)。其在肌肉耐力及肌肉再生功能扮演重要角色。我們建立NRIP剔除鼠,是肌肉萎縮症的動物模型 (USA patent; JCS 2015)。肌肉再生現象必須仰賴成人幹細胞的活化、增生以及進一步分化才能達成。因此NRIP參與肌肉再生及衛星細胞的活化我們繼續探索問題。另外,NRIP也和運動神經元之發育有關。我們又建立肌肉剔除NRIP老鼠,藉以了解肌肉NRIP對於運動神經元的影響。另外NRIP calmodulinACTN2結合,我們正在研究這三個蛋白質結合和鈣離子關係及對心臟的纖維結構及心臟功能的影響。

2.         另一則是BCAS2. BCAS2為一核蛋白質。BCAS2有兩種功能,一是p53的負調控因 (Cancer Research, 2009; British Journal of Cancer, 2015);另一參與核糖核酸剪切。我們利用果蠅系統發現BCAS2具有RNA剪接功能及對果蠅生長發育有關RNA, 2013; Plos One 2015. 目前我們利用條件式的剃除鼠研究BCAS2影響腦海馬迴學習及記憶的調控基轉,希望能建立失智或失意的老鼠動物模式,提供未來診斷與治療的平台 (Scientific Reports, 2016)

3.         利用病毒為載的基因治療做為上述我們建立的人類疾病動物模式進行治療評估

4.         HPV 和子癌的關係. NRIP透過質固醇受體與HPV E2病毒蛋白調控HPV基因表現 (JV 2011; Virology 2012)另外E2如何保持viral genome 分配至host cell 也是探索問題 (Plos One, 2014)  

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研究室成員

博士生:吳曉慧、陳信雄、黃楚崴
碩士生:柯文斌、彭瀞儀、黃韻心、韋伯翰、顏婉欣、林詩浩

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研究成果

PUBLICATIONS [Selected Papers; * corresponding author]

1.*Chu-Wei Huang, Yi-Wen Chen, Yi-Rou Lin, Po-Han Chen, Meng-Hsuan Chou, Li-Jen Lee, Pei-Yu Wang, June-Tai Wu, Yeou-Ping Tsao, and Show-Li Chen. 2016. Conditional Knockout of Breast Carcinoma Amplified Sequence 2 (BCAS2) in Mouse Forebrain Causes Dendritic Malformation via beta-catenin. Scientific Reports, 6: 34927.
2.*Chen Hsing-Hsung, Chen Wen-Pin, Yan War-Lon, Huang Yuan-Chun, Chang Szu-Wei, Fu Wen-Mei, Su Ming-Jai, Yu I-Shing, Tsai Tzung-Chieh, Yan Yu-Ting, Tsao Yeou-Ping, and Chen Show-Li. 2015. NRIP is newly identified as a Z-disc protein, activating calmodulin signaling for skeletal muscle contraction and regeneration. Journal of Cell Science, 128: 4196-4209.
3.*Chou Meng-Hsuan, Hsieh Yi-Chen, Huang Chu-Wei, Chen Po-Han, Chan Shih-Peng, Tsao Yeou-Ping, Lee Hsiu-Hsiang, Wu June-Tai, Chen Show-Li. 2015. BCAS2 regulates Delta-Notch signaling activity through Delta pre-mRNA splicing in Drosophila wing development. Plos One 10:e0130706.
4.*Kuo Ping-Chang, Huang Chu-Wei, Lee Chia-I, Chang Hung-Wei, Hsieh Swen-Wan, Chung Yu-Ping, Lee Ming-Shyue, Huang Chiun-Sheng, Tsao Li-Pen, Tsao Yeou-Ping, Chen Show-Li. 2015. BCAS2 Promotes Prostate Cancer Cells Proliferation by Enhancing AR mRNA Transcription and Protein Stability. British Journal of Cancer, 112: 391-402.
5.*Chang Szu-Wei, Liu Wei-Chen, Liao Kuan-Yu, Tsao Yeou-Ping, Hsu Pang-Hung, Chen Show-Li. 2014. Phosphorylation of HPV-16 E2 at serine 243 enables binding to Brd4 and mitotic chromosomes. Plos One 9: e110882.
6.*Chen, Po-Han, Lee Chia-I Lee, Weng Yu-Tzu, Tarn Woan-Yuh, Tsao Yeou-Ping, Kuo Ping-Chang, Hsu Pang-Hung, Huang Chu-Wei, Huang Chiun-Sheng, Lee Hsiu-Hsiang, Wu June-Tai, Chen Show-Li. 2013. BCAS2 is essential for Drosophila viability and functions in pre-mRNA splicing. RNA 19: 208-218.
7.*Chang Szu-Wei, Su Chieh-Hao, Chen, Hsuan-Hao, Huang Chu-Wei, Tsao Li-Pen, Tsao Yeou-Ping, Chen Show-Li. 2012. DDB2 is a novel AR interacting protein and mediates AR ubiquitination/degradation. International Journal of Biochemistry & Cell Biology 44: 1952-1961.
8.*Chang Szu-Wei, Lu Pei-Yu, Guo Jih-Huong, Tsai Tzung-Chieh, Tsao Yeou-Ping, Chen Show-Li. 2012. NRIP Enhances HPV Gene Expression via Interaction with Either GR or E2. Virology, 423: 38-48.
9.*Chang Szu-Wei, Tsao Yeou-Ping, Lin Chia-Yi, Chen, Show-Li.. 2011. NRIP, a novel calmodulin binding protein, activates calcineurin to dephosphorylate HPV E2 protein Journal of Virology, 85: 6750-6763.
10.Zhou L, Zhu T, Ye X, Yang L, Wang B, Liang X, Lu L, Tsao YP, Chen SL, Li J, Xiao X. 2010. Long-term protection against HPV E7-positive tumor by a single vaccination of AAV vectors encoding a fusion protein of inactivated E7 of HPV 16/18 and heat shock protein 70. Human Gene Therapy 21: 109-119.
11.*Kuo Ping-Chang, Tsao Yeou-Ping, Chang Hung-Wei, Chen Po-Han, Huang Chu-Wei, Lin Shinn-Tsuen, Weng Yu-Tzu, Tsai Tzung-Chieh, Shieh Sheau-Yann, Chen Show-Li. 2009. Breast cancer amplified sequence 2., a novel negative regulator of the p53 tumour suppressor. Cancer Research 69: 8877-8885.
12.*Chen Pei-Hong, TsaoYeou-Ping, Wang Chih-Chiang, Chen Show-Li. 2008. NUCLEAR RECEPTOR INTERACTION PROTEIN, a coactivator of ANDROGEN RECEPTORS (AR), is regulated by AR and Sp1 to feed forward activate its own gene expression through AR protein stability. Nucleic Acids Research 36: 51-66.
13.Han CP, Lee MY, Tzeng SL, Yao CC, Wang PH, Cheng YW, Chen SL, Wu TS, Tyan YS, Kok LF.2008. Nuclear Receptor Interaction Protein (NRIP) expression assay using human tissue microarray and immunohistochemistry technology confirming nuclear localization. J Exp Clin Cancer Res. 2;27:25
14.*Chen Show-Li, Lin Shinn-Tsuen, Tsai Tzung-Chieh, Hsiao Wei-Chih, Tsao Yeou-Ping. 2007. ErbB4 (JM-b/CYT-1) induced expression and phosphorylation of c-Jun is diminished by human papillomavirus type 16 E5 protein. Oncogene 26: 42-53.
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