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張茂山 Dr. Mau-Sun Chang

專任教授

【學歷】
1993-1997 國立臺灣大學 動物學研究所 博士
1992-1993 國立臺灣大學 動物學研究所 碩士
1985-1989 國立臺灣大學 動物系 學士
 
【經歷】
2023-至今 國立臺灣大學生化科學研究所 教授
2012-2023 國立臺灣大學生化科學研究所 副教授
2008-至今 中央研究院生物化學研究所 合聘助研究員
2008-2012 國立臺灣大學生化科學研究所 助理教授
2005-2008 馬偕紀念醫院醫研部 研究員
1999-2004 馬偕紀念醫院醫研部 副研究員
1997-1999 Postdoc fellow, Dana-Farber Cancer Institute, Harvard Medical School
 
【研究領域與專長】
一、PHRF1與DNA damage和癌症生成之研究
PHRF1具有可辨認甲基化組蛋白的plant homeodomain (PHD)和可對受質進行泛素化的E3 ligase domain，我們發現PHRF1連接甲基化H3K36和Nbs1使得PHRF1在DNA雙股斷裂時調控細胞的非同源性末端接合 (Non-homologous end joining, NHEJ) (圖一)。PHRF1利用C端的SRI domain和RNA Pol II最大次單元Rpb1作用，影響Zeb1的轉錄作用進而影響肺癌細胞的侵襲能力(圖二)。

圖一、A schematic model of PHRF1 in NHEJ repair.
 

圖二、A schematic model for PHRF1 to modulate ZEB1’s transcription.


二、建立KrasG12D, p53fl/fl和PHRF1fl/fl 三基因突變誘導自發性產生膽管癌/肝癌小鼠模型

圖三、KrasG12D, p53fl/fl和PHRF1fl/fl 三基因突變自發性產生膽管癌/肝癌小鼠
 
【近年著作】

2023 Lee JY, Chou NL, Yu YR, Shih HA, Lin HW, Lee CK, Chang MS. PHRF1 promotes the class switch recombination of IgA in CH12F3-2A cells. PLoS One. 2023 18:e0285159. 
2021 Lin HW, Lee JY, Chou NL, Shih TW, Chang MS. Phosphorylation of PUF-A/PUM3 on Y259 modulates PUF-A stability and cell proliferation. PLoS One. 2021 16:e0256282
2020 Lee JY, Fan CC, Chou NL, Lin HW, Chang MS. PHRF1 promotes migration and invasion by modulating ZEB1 expression. PLoS One. 2020 15:e0236876.
Shih TW, Lee LJ, Chang HC, Lin HW, Chang MS. An important role of PHRF1 in dendritic architecture and memory formation by modulating TGF-β signaling. Sci Rep. 2020 10:10857.
Fan JJ, Hsu WH, Lee KH, Chen KC, Lin CW, Lee YA, Ko TP, Lee LT, Lee MT, Chang MS*, Cheng CH*. Dietary Flavonoids Luteolin and Quercetin Inhibit Migration and Invasion of Squamous Carcinoma through Reduction of Src/Stat3/S100A7 Signaling. Antioxidants (Basel). 2019 8:557. (* Corresponding author)
2017 Lee JY, Lee LJ, Fan CC, Chang HC, Shih HA, Min MY, Chang MS. Important roles of Vilse in dendritic architecture and synaptic plasticity. Sci Rep. 2017 7:45646.
2016 Su WP, Hsu SH, Chia LC, Lin JY, Chang SB, Jiang ZD, Lin YJ, Shih MY, Chen YC, Chang MS, Yang WB, Hung JJ, Hung PC, Wu WS, Myung K, Liaw H (2016, Jan). Combined Interactions of Plant Homeodomain and Chromodomain Regulate NuA4 Activity at DNA Double-Strand Breaks. Genetics, 202:77-92.2015
2015 Chang CF, Chu PC, Wu PY, Yu MY, Lee JY, Tsai MD, *Chang MS. PHRF1 promotes genome integrity by modulating non-homologous end-joining. Cell Death Dis. 2015 6:e1716.
2014 Zhong W, Zhou Y, Li J, Mysore R, Luo W, Li S, Chang MS, Olkkonen VM, Yan D. OSBP-related protein 8 (ORP8) interacts with Homo sapiens sperm associated antigen 5 (SPAG5) and mediates oxysterol interference of Hep2 cell cycle. Exp Cell Res 2014 322:227-35.
Cheng CH, Chou CM, Chu CY, Chen GD, Lien HW, Hwang PP, Chang MS, Huang CJ. Differential regulation of Tetraodon nigroviridis Mx gene promoter activity by constitutively-active forms of STAT1, STAT2, and IRF9. Fish Shellfish Immunol. 2014 38:230-243.
2013 Fan CC, Lee LY, Yu MY, Tzen CY, Chou C, Chang MS*. Upregulated hPuf-A promotes breast cancer tumorigenesis. Tumor Biol. 2013, 34:2557-2564.
Chen YL, Jiang YW, Su YL, Lee SC, Chang MS, Chang CJ. Transcriptional regulation of tristetraprolin by NF-κB signaling in LPS-stimulated macrophages. 2013, Mol. Biol. Rep. 40:2867-2877. (IF: 2.506; Ranking: Biochemistry & Molecular Biology 172/290)
2012 Chen YL, Jiang YW, Su YL, Lee SC, Chang MS, Chang CJ, 2012, “Transcriptional regulation of tristetraprolin by NF-kappaB signaling in LPS-stimulated macrophages.”, Molecular biology reports, Mol Biol Rep (2013) 40, 2867-77.
Yeh PA, Yang WH, Chiang PY, Wang SC, Chang MS, Chang CJ, 2012, “Drosophila eyes absent is a novel mRNA target of the tristetraprolin (TTP) protein DTIS11.”, International journal of biological sciences, 8(5), 606-19.
Chen CH, Chu PC, Lee L, Lien HW, Lin TL, Fan CC, Chi P, Huang CJ, Chang MS*, 2012, “Disruption of Murine mp29/Syf2/Ntc31 Gene Results in Embryonic Lethality with Aberrant Checkpoint Response.”, PloS one, 7(3), e33538.
2011 Chang HY, Fan CC, Chu PC, Hong BE, Lee HJ, Chang MS*, 2011, “hPuf-A/KIAA0020 Modulates PARP-1 Cleavage upon Genotoxic Stress.”, Cancer research, 71(3), 1126-34.
2009 Chu PC, Wang TY, Lu YT, Chou CK, Yang YC, Chang MS*, 2009, “Involvement of p29 in DNA damage responses and Fanconi anemia pathway.”, Carcinogenesis, 30(10), 1710-1716.
2008 Cheng TS, Hsiao YL, Lin CC, Yu CT, Hsu CM, Chang MS, Lee CI, Huang CY, Howng SL, Hong YR, 2008, “Glycogen synthase kinase 3beta interacts with and phosphorylates the spindle-associated protein astrin.”, The Journal of biological chemistry, 283(4), 2454-64.