冀宏源 Dr. Hung-Yuan (Peter)Chi

特聘教授、所長

Youtube影片►【大專生暑期生化實習計畫

【學歷】
2003-2007 美國耶魯大學 分子生物物理生化系 博士
Ph.D., Department of Molecular Biophysics and Biochemistry, Yale University
 
【經歷】
2020-至今 國立臺灣大學生化科學研究所 所長兼任生命科學院副院長
2020-至今 中央研究院生物化學研究所 合聘研究員
2019-至今 國立臺灣大學生化科學研究所 教授
2018-2020 中央研究院生物化學研究所 合聘副研究員
2014-2019 國立臺灣大學生化科學研究所 副教授
2010-2014 國立臺灣大學生化科學研究所 助理教授
2011-2018 中央研究院生物化學研究所 合聘助研究員
2010-2010 美國耶路大學 分子生物物理生化系 博士後研究
2008-2010 美國洛克斐勒大學 博士後研究
 

【我們的研究主題】

(1) 研究基因重組機制調控生物基因完整性之分子作用機轉。包含受損DNA的修復、停滯之DNA複製的重啟、以及端粒長度的維持。
(2) 進一步探討由基因修復失調所引發的癌症之形成,和利用癌細胞基因修復的缺失來達到個人化的精準醫療策略。

圖一、基因修復失調導致癌症的發生

 

【我們如何進行研究】

(1) 以生化實驗來研究基因重組機制,及如何穩定基因組完整性之作用機轉。
(2) 以細胞分生實驗來研究DNA損傷的修復、基因穩定性、和癌症之機制。
 

【我們使用的研究技術】

為了探討同源重組相關的生物課題,我們實驗室藉由大腸桿菌或動物細胞(酵母菌、昆蟲、及人類細胞)來表達及純化欲研究之蛋白質,並以生物化學、生物物理、及生物結構等實驗方法,來讓我們得以觀察該蛋白質的特性,以及研究其調控之分子機制;此外我們也體外培養人類細胞,並操控該蛋白質在細胞內的表現與否,得以檢視該蛋白質對細胞層面的影響。我們藉由了解蛋白質的生化特性去闡釋其分子作用機制,並進一步解釋其生物生理功能。

圖二、從生物化學、生物物理、生物結構及細胞層次來探討基因修復的分子機轉。

【我們的跨領域合作】

  我們與臺大化學系合作,以單分子生物物理的方法學,更深入地觀察單分子蛋白質與DNA在微觀尺度下的相互作用變化和動態過程。我們與中研院冷凍電顯中心合作,透過尖端設備來解析蛋白質結構,藉由蛋白質的功能性結構進一步闡釋其分子作用機制。我們也與多國的研究團隊做學術交流,整合了多層次及跨領域的研究方法,如分子遺傳學、細胞學、生物化學和結構生物學,共同來闡明同源重組相關的生化機制。
  此外我們也與臨床醫師合作,期望我們在修復受損基因的分子機轉了解,不僅在基礎研究上有所突破,在未來癌症預防及治療上更有其應用性。我們相信互補性及跨領域的研究合作,不但能使我們對研究的課題,有更全面及深入的理解,也能使學生在學習領域的廣度和深度上,及與他人合作的互動中,有更多的學習與自我成長。

【我們的實驗室風格~~4H

我們是一個對科學研究充滿熱忱的實驗室,注重團隊合作、氣氛融洽,4H是我們的風格。


【近年著作】

2021 Li, W.C., Lee, C.Y., Lan, W.H., Woo, T.T., Liu, H.C., Yeh, H.Y., Chang, H.Y., Chuang, Y.C., Chen, C.Y., Chuang, C.N., Chen, C.L., Hsueh, Y.P., Li, H.W.*, Chi, P.*, and Wang, T.F.* (2021) Trichoderma reesei Rad51 tolerates mismatches in hybrid meiosis with diverse genome sequences. Proc Natl Acad Sci U S A., 118(8):e2007192118.
Luo, S.C., Yeh, H.Y., Lan, W.H., Wu, Y.M., Yang, C.H., Chang, H.Y., Su, G.C., Lee, C.Y., Wu, W.J., Li, H.W., Ho, M.C.*., Chi, P.*, and Tsai, M.D.* (2021) Identification of fidelity-governing factors in human recombinases DMC1 and RAD51 from cryo-EM structures. Nature Communications, 12(1):115.
Lyu, X., Lei, K.H., Biak Sang, P., Shiva, O., Chastain, M., Chi, P.*, and Chai, W.* (2021) Human CST complex protects stalled replication forks by directly blocking MRE11 degradation of nascent-strand DNA. EMBO J., 40(2):e103654.
2020 Chang, H.Y., Lee, C.Y., Lu, C.H., Lee, W., Yang, H.L., Yeh, H.Y., Li, H.W.*, Chi, P.* (2020) Microcephaly family protein MCPH1 stabilizes RAD51 filaments, Nucleic Acids Res., In press
Lan, W.H., Lin, S.Y., Kao, C.Y., Chang, W.H., Yeh, H.Y., Chang, H.Y., Chi, P.*, and Li, H.W.* (2020) Rad51 facilitates filament assembly of meiosis-specific Dmc1 recombinase. Proc Natl Acad Sci U S A., 117(21): 11257-11264
2019 Lee, C.-Y., Su, G.-C., Huang, W.-Y., Ko, M.-Y., Yeh, H.-Y., Chang, G.-D., Lin, S.-J., & Chi, P*. (2019) Promotion of homology-directed DNA repair by polyamines, Nature Communications, 10:65
Klein, H.L., .., Chi P, Heyer, W.D., .., Niu, H., and Rothenberg, E. (2019) Guidelines for DNA recombination and repair studies: Mechanistic assays of DNA repair processes, Microbial Cell, 6(1): 65–101.
2018 Lu, C.-H., Yeh, H.-Y., Su, G.-C., Ito, K., Kurokawa, Y., Iwasaki, H.*, Chi, P.*, & Li, H.-W.* (2018) Swi5-Sfr1 Stimulates Rad51 Recombinase Filament Assembly by Modulating Rad51 Dissociation, Proc. Nat. Acad. Sci. U.S.A., 115(43):E10059-E10068.
2017 Huang, W.Y., Lai, S.F., Chiu, H.Y., Chang, M., Plikus, M., Chan, C.C., Chen, Y.T., Tsao, P.N., Yang, T.L., Lee, H.S., Chi, P., and Lin, S.J. (2017) Mobilizing transit-amplifying cell-derived ectopic progenitors prevents hair loss from chemotherapy or radiation therapy. Cancer Research, 77 (22):6083-6096.
Yeh, H.Y., Lin, S.W., Wu, Y.C., Chan, N.L., and Chi, P*. (2017) Functional characterization of the meiosis-specific DNA double-strand break inducing factor SPO-11 from C. elegans. Scientific Reports, 7(1):2370
2016 Chao, A., Chang, T.C., Lapke, N., Jung, S.M., Chi, P., Chen, C.H., Yang, L.Y., Lin, C.T., Huang, H.J., Chou, H.H., Liou, J.D., Chen, S.J., Wang, T.H., and Lai, C.H. (2016) Prevalence and clinical significance of BRCA1/2 germline and somatic mutations in Taiwanese patients with ovarian cancer. Oncotarget, 7(51):85529-41.
Su, G.C., Yeh, H.Y., Lin, S.W., Chung, C.I., Huang, Y.S., Liu, Y.C., Lyu, P.C., and Chi, P*. (2016) Role of the RAD51-SWI5-SFR1 ensemble in homologous recombination. Nucleic Acids Res., 44(13):6242-51.
2015 Chang, H.Y., Liao, C.Y., Su, G.C., Lin, S.W., Wang, H.W., Chi, P. (2015) Functional Relationship of ATP Hydrolysis, Presynaptic Filament Stability, and Homologous DNA Pairing Activity of the Human Meiotic Recombinase DMC1. J Biol Chem., 290(32):19863-73.
2014 Zhao, W., Saro, D., Hammel, M., Kwon, Y., Xu, Y., Rambo, R.P., Williams, G.J., Chi, P., Lu, L., Pezza, R.J., Camerini-Otero, R.D., Tainer, J.A., Wang, H.W., Sung, P. (2014) Mechanistic insights into the role of Hop2-Mnd1 in meiotic homologous DNA pairing. Nucleic Acids Res., 42(2):906-17.
Su, G.C., Chung, C.I., Liao, C.Y., Lin, S.W., Tsai, C.T., Huang, T., Li, H.W., Chi, P. (2014) Enhancement of ADP release from the RAD51 presynaptic filament by the SWI5-SFR1 complex. Nucleic Acids Res., 42(1):349-58.
2013 Wilson, M.A., Kwon, Y., Xu, Y., Chung, W.H., Chi, P., Niu, H., Mayle, R., Chen, X., Malkova, A., Sung, P., Ira, G. (2013) Pif1 helicase and Polδ promote recombination-coupled DNA synthesis via bubble migration. Nature, 502(7471):393-6.
Busygina, V., Gaines, W.A., Xu, Y., Kwon, Y., Williams, G.J., Lin, S.W., Chang, H.Y., Chi, P., Wang, H.W., and Sung, P. (2013) Functional attributes of the Saccharomyces cerevisiae meiotic recombinase Dmc1. DNA Repair (Amst), 12(9):707-12.
2012 Tsai, S.P., Su, G.C., Lin, S.W., Chung, C.I., Xue, X., Dunlop, M.H., Akamatsu, Y., Jasin, M., Sung, P., and Chi, P. (2012) Rad51 presynaptic filament stabilization function of the mouse Swi5-Sfr1 heterodimeric complex.Nucleic Acids Res., 40 (14):6558-69.
Chen, C.H., Chu, P.C., Lee, L., Lien, H.W., Lin, T.L., Fan, C.C., Chi, P., Huang, C.J., and Chang, M.S. (2012) Disruption of murine mp29/Syf2/Ntc31 gene results in embryonic lethality with aberrant checkpoint response. PLoS One, e33538.
2011 Chi, P., Kwon, Y., Visnapuu, M.L., Lam, I., Santa Maria, S.R., Zheng, X., Epshtein, A., Greene, E.C., Sung, P., and Klein, H.L. (2011) Analyses of the yeast Rad51 recombinase A265V mutant reveal different in vivo roles of Swi2-like factors. Nucleic Acids Res., 1-12.
2010 Niu, H., Chung, W.H., Zhu, Z., Kwon, Y., Zhao, W., Chi, P., Prakash, P., Seong, C., Liu, D., Lu, L., Ira, G., and Sung, P. (2010) Mechanism of the ATP-dependent DNA end-resection machinery from Saccharomyces cerevisiae. Nature, 467(7311):108-11.
2009 Robertson, R.B., Moses, D.N., Kwon, Y., Chan, P., Chi, P., Klein, H., Sung, P., and Greene, E.C. (2009) Structural transitions within human Rad51 nucleoprotein filaments. PNAS, 106(31):12688-93.
Chi, P., Kwon, Y., Moses, D.N., Seong, C., Sehorn, M.G., Singh, A.K., Tsubouchi, H., Greene, E.C., Klein, H.L., and Sung, P. (2009) Functional interactions of meiotic recombination factors Rdh54 and Dmc1. DNA Repair (Amst), 8(2):279-84.
Robertson, R.B., Moses, D.N., Kwon, Y., Chan, P., Chi, P., Klein, H., Sung, P., and Greene, E.C., (2009) Visualizing the disassembly of S.cerevisiae Rad51 nucleoprotein filaments. J. Mol. Biol., 388(4):703-20.
2008 Seong, C., Sehorn, M.G., Plate, I., Shi, I., Song, B., Chi, P., Mortensen, U., Sung, P., and Krejci, L. (2008) Molecular anatomy of the recombination mediator function of Saccharomyces cerevisiae Rad52. J. Biol. Chem., 283(18):12166-74.
Kwon, Y., Seong, C., Chi, P., Greene, E.C., Klein, H., and Sung, P. (2008) ATP-dependent chromatin remodeling by the Saccharomyces cerevisiae homologous recombination factor Rdh54/Tid1. J. Biol. Chem., 283(16):10445-52.
2007 Hu, Y., Raynard, S., Sehorn, M.G., Lu, X., Bussen, W., Zheng, L., Stark, J.M., Barnes, E.L., Chi, P., Janscak, P., Jasin, M., Vogel, H., Sung, P., and Luo, G. (2007) RECQL5/Recql5 helicase regulates homologous recombination and suppresses tumor formation via disruption of Rad51 presynaptic filaments. Genes & Develop., 21(23):3078-84.
Chi, P., San Filippo, J., Sehorn, M.G., Petukhova, G.V., and Sung, P. (2007) Bipartite stimulatory action of the Hop2-Mnd1 complex on the Rad51 recombinase. Genes & Develop., 21(14):1747-57.
Kwon,Y., Chi, P., Roh, D. H., Klein, H., and Sung, P. (2007) Synergistic action of the Saccharomyces cerevisiae homologous recombination factors Rad54 and Rad51 in chromatin remodeling. DNA Repair (Amst), 6(10):1496-506.
Prasad, T.K., Robertson, R.B., Visnapuu, M.L., Chi, P., Sung, P., and Greene, E.C. (2007) A DNA-translocating Snf2 molecular motor: Saccharomyces cerevisiae Rdh54 displays processive translocation and extrudes DNA loops. J. Mol. Biol., 369(4):940-53.
2006 Chi, P., Kwon, Y., Seong, C., Epshtein, A., Lam, I., Sung, P., and Klein, H. L. (2006) Yeast recombination factor Rdh54 functionally interacts with the Rad51 recombinase and catalyzes Rad51 removal from DNA. J. Biol. Chem., 281(36):26268-79.
Chi, P., Van Komen, S., Sehorn, M.G., Sigurdsson, S., and Sung, P. (2006) Roles of ATP binding and ATP hydrolysis in human Rad51 recombinase function. DNA Repair (Amst), 5(3): 381-91.
San Filippo, J., Chi, P., Sehorn, M.G., Etchin, J., Krejci, L., and Sung, P. (2006) Recombination mediator and Rad51 targeting activities of a human BRCA2 polypeptide. J. Biol. Chem., 281 (17):11649-57.
2004 Raschle, M., Van Komen, S., Chi, P., Ellenberger, T., and Sung, P. (2004) Multiple interactions with the Rad51 recombinase govern the homologous recombination function of Rad54. J. Biol.Chem., 279(50):51973-80.
1998 Chi, P., Doong, S.L., Lin-Shiau, S.Y., Boone, C. W., Kelloff, G. J., and Lin, J.K. (1998) Oltipraz, a novel inhibitor of hepatitis B virus transcription through elevation of p53 protein. Carcinogenesis,19(12):2133-2138. (Note: my name was Wei-Jie Chi in the publication)