獲獎人簡介 ▞
冀宏源 Hung-Yuan (Peter) Chi, PhD
冀宏源老師為現任國立台灣大學生化科學研究所特聘教授,兼任中央研究院生物化學研究所合聘研究員,並擔任台灣大學生化所所長和生命科學院副院長。他的研究主軸為同源染色體基因重組機制,包括受損基因的修復、基因複製停滯後的重啟,以及端粒長度的維持。冀老師的實驗室利用大腸桿菌和各種細胞(如酵母菌、昆蟲和人類細胞),透過生化和細胞生物學實驗來探討細胞如何能夠精準地修復受損基因,進而維持基因體的穩定。此外,他也研究由基因修復失調所引發的癌症,並期望透過增進對基因修復的理解,有助於針對基因修復失調引發的癌症進行預防和精準治療。
Education 學歷 ▞
美國耶魯大學 分子生物物理生化系 博士 2008
國立台灣大學 生化科學研究所 碩士 1998
國立臺灣海洋大學 食品科學系 學士 1996
Current Position 現職 ▞
中央研究院生物化學所 合聘研究員 2020 - 迄今
國立臺灣大學 生化科學研究所 教授 2019 - 迄今
Honors 榮譽獎項 ▞
科技部傑出研究獎 2023
傑出教師 2022
優良教師 2021
科技部傑出研究獎 2020
優良教師 2020
科技部未來科技獎 2017
科技部指導大專學生研究計畫創作獎 2017
中央研究院年輕學者研究著作獎 2016
吳大猷先生紀念獎 2015
優秀年輕學者研究計畫 生物化學及分子生物學門 2015
傑出教師 2014
優良教師 2013
Publications 學術論文發表 ▞
(標記*為通訊作者)
Jaiswal, R.K., Lei, K.H., Chastain, M., Wang, Y., Shiva, O., Li, S., You, Z., Chi, P., and Chai, W. (2023) CaMKK2 and CHK1 phosphorylate human STN1 in response to replication stress to protect stalled forks from aberrant resection. Nature Communications, 14(1):7882.
Lee, C.Y., Cheng, W.F., Lin, P.H., Chen, Y.L., Huang, S.H., Lei, K.H., Chang, K.Y., Ko, M.Y., and Chi, P.* (2023) An activity-based functional test for identifying homologous recombination deficiencies across cancer types in real-time. Cell Reports Medicine, 4(11):101247.
Guh, C.L., Lei, K.H., Chen, Y.A., Jiang, Y.Z., Chang, H.Y., Liaw, H., Li, H.W., Yen, H.Y., and Chi, P.* (2023) RAD51 paralogs synergize with RAD51 to protect reversed forks from cellular nucleases. Nucleic Acids Res., 51(21):11717-11731.
Luo, S.C., Yeh, M.C., Lien, Y.H., Yeh, H.Y., Siao, H.L., Tu, I.P., Chi, P., and Ho, M.C. (2023) A RAD51–ADP double filament structure unveils the mechanism of filament dynamics in homologous recombination. Nature Communications, 14(1): 4993.
Liu, C.C., Chan, H.R., Su, G.C., Hsieh, Y.Z., Lei, K.H., Kato, T., Yu, T.Y., Kao, Y.W., Cheng, T.H., Chi, P.*, and Lin, J.J. (2023) Flap endonuclease Rad27 cleaves the RNA of R-loop structures to suppress telomere recombination. Nucleic Acids Res., 51(9):4398-4414.
Ho, Y.C., Ku, C.S., Tsai, S.S., Shiu, J.L., Jiang, Y.Z., Miriam, H.E., Zhang, H.W., Chen, Y.T., Chiu, W.T., Chang, S.B., Shen, C.H., Myung, K., Chi, P., and Liaw, H. (2022) PARP1 recruits DNA translocases to restrain DNA replication and facilitate DNA repair. PLoS Genet., 13;18(12):e1010545.
Blay, V., Gailiunaite, S., Lee, C. Y., Chang, H. Y., Hupp, T., Houston, D. R., and Chi, P. (2022) Comparison of ATP-binding pockets and discovery of homologous recombination inhibitors. Bioorganic & Medicinal Chemistry, 70:116923.
Lei, K.H., Yang, H.L., Chang, H.Y., Yeh, H.Y., Nguyen, D.D., Lee, T.Y., Lyu, X., Chastain, M., Chai, W., Li, H.W., and Chi, P.* (2021) Crosstalk between CST and RPA regulates RAD51 activity during replication stress. Nature Communications, 12(1):6412.
Hinman, A. W., Yeh, H.Y., Roelens, B., Yamaya, K., Woglar, A., Bourbon, H-M. G., Chi, P., and Villeneuve, A.M. (2021) Caenorhabditis elegans DSB-3 reveals conservation and divergence among protein complexes promoting meiotic double-strand breaks. Proc Natl Acad Sci U S A., 118(33):e2109306118.
Chen, W.T., Tseng, H.Y., Jiang, C.L., Lee, C.Y., Chi, P., Chen, L.Y., Lo, K.Y., Wang, I.C., and Lin, F.J. (2021) Elp1 facilitates RAD51-mediated homologous recombination repair via translational regulation. J Biomed Sci., 28(1):81.
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.
Chang, H.Y., Lee, C.Y., Lu, C.H., Lee, W., Yang, H.L., Yeh, H.Y., Li, H.W., and Chi, P.* (2020) Microcephaly family protein MCPH1 stabilizes RAD51 filaments. Nucleic Acids Res., 48(16):9135-46.
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.
Lee, C.Y., Su, G.C., Huang, W.Y., Ko, M.Y., Yeh, H.Y., Chang, G.D., Lin, S.J., and Chi, P.*. (2019) Promotion of homology-directed DNA repair by polyamines, Nature Communications, 10(1):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.
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 Natl Acad Sci U S A.,115(43):E10059-E10068.
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
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.
Chang, H.Y., Liao, C.Y., Su, G.C., Lin, S.W., Wang, H.W., and 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.
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.
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.
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., 7(3):e33538
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., 39(15):6511-22.
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.
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.
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.
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.
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.
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.
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)