【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
(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
(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。
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。
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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) |
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