复旦大学基础医学院研究生导师简介-徐彦辉教授

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　　姓名：徐彦辉 博士
　　职称：研究员
　　E-MAIL:xuyh@fudan.edu.cn
　　WWW: http://www.xulab.fudan.edu.cn
　　研究方向
　　1.DNA甲基化关键蛋白(DNMT1， DNMT3，UHRF1，TET1/2/3)，组蛋白甲基化修饰调控酶(LSD2，KDM7A)的催化，底物识别及酶活性调节的分子机制，以及DNA甲基化与组蛋白甲基化之间相互调节的机制。
　　2.染色质结构调控，DNA损伤修复等方面蛋白质复合物的结构功能研究。
　　3.基于结构的药物设计，筛选和优化工作，开发用于研究或临床(抗肿瘤)的化合物。
　　重要学术贡献
　　系统的阐明了DNA甲基化和组蛋白甲基化修饰(二者有密切关联并互相调节)关键酶的催化，底物识别和酶活性调节的分子机制，在表观遗传调控领域取得了突出成绩。
　　1、阐明了TET2催化及识别甲基化DNA底物的分子机制。首次报道了氧化DNA甲基化修饰关键蛋白TET2和DNA底物的复合物晶体结构(Cell, 2013)，阐明了TET蛋白识别DNA底物的分子机制，对DNA甲基化动态调控研究起到重要的推动作用。
　　2、阐明了组蛋白激活DNMT3A调节DNA甲基化建立的分子机制(Nature, 2015)。阐明了UHRF1和DNMT1指导DNA甲基化维持的分子机制(Nature Communications，2015;Cell Res, 2011; J BiolChem, 2013)，揭示了UHRF1蛋白水平随细胞周期动态变化的机理(PNAS, 2012)。
　　3、阐明了组蛋白去甲基化酶的识别及活性调节机制。发现LSD2存在“双底物识别位点”(Cell Res, 2013)，阐明NPAC蛋白激活LSD2酶活性的机制(Mol Cell, 2013);发现LSD2具有E3泛素连接酶活性并抑制癌细胞生长(Mol Cell, 2015)。
　　荣誉与获奖
　　1、2016 教育部 自然科学一等奖(第一完成人)
　　2、2016 中国科协 中国青年科技人才奖
　　3、2016 中国科协 中国青年科技奖
　　4、2016 中国科学院大学/中源协和 中源协和生命医学创新突破奖
　　5、2015 上海市生物医药行业协会 谈家桢生命科学奖(创新奖)
　　6、2015 药明康德公司 药明康德生命化学奖(学者奖)
　　7、2015 树兰医学奖基金 树兰医学青年奖
　　8、2014 上海市科协 上海市青年科技英才奖
　　9、2012 国家人类基因组南方研究中心 明治生命科学奖(杰出奖)
　　10、2012 上海市生物物理学会 上海市生物物理学科青年科技英才
　　11、2011 中国生物物理学会 贝时璋青年生物物理学家奖
　　国内外学术团体任职
　　1. 2017.11-2021.10 中国生物物理学会第十一届理事会 理事
　　2. 2015.11-2017.10 中国生物物理学会分子生物物理分会 理事
　　3. 2013.11-2017.10 中国生物物理学会 理事
　　受邀审稿学术刊物
　　校内学术机构任职
　　……
　　受邀学术报告
　　1、徐彦辉，Structural Basis for the Regulation of DNA Methylation，世界生物生命科学大会，北京，2016.11.01
　　2、徐彦辉，Structural basis for the regulation of DNA methylation，华人生物学家大会，成都，2016.08
　　3、徐彦辉，Substrate preference for TET-mediated oxidation，冷泉港(亚洲)会议：CHROMATIN, EPIGENETICS & TRANSCRIPTION，苏州，2016.05
　　4、徐彦辉，Crystal Structure of TET2-DNA Complex: Insight into TET-mediated 5mC Oxidization，冷泉港(亚洲)会议：Epigenetics, Chromatin, and Transcription，苏州，2014.05.05-2014.05.09
　　5、徐彦辉，Structural Insight into TET-mediated iterative Oxidization of 5-Methyl-Cytosine，冷泉港(亚洲)会议: Structural Biology - From Atoms to Cells，苏州，2014.06.09-2014.06.13
　　6、徐彦辉，Molecular Basis for the Regulation of DNA Methylation，Cell LabLinks - Structural Biology Frontiers: From Membrane to Chromatin，北京，2014.05.15
　　7、徐彦辉，Molecular Mechanism of Substrate Recognition and Enzymatic Activity Regulation of Histone Demethylases，第四届中国结构生物学学术讨论会，重庆，2013.03.31-2013.04.03
　　发表论文
　　2018
　　1.Rao, Q., Liu, M., Tian, Y., Wu, Z., Hao, Y., Song, L., Qin, Z., Ding, C., Wang, H. W.*, Wang, J*, and Xu, Y.* (2018) Cryo-EM structure of human ATR-ATRIP complex. Cell research 28, 143-156
　　2.He, X. D., Gong, W., Zhang, J. N., Nie, J., Yao, C. F., Guo, F. S., Lin, Y., Wu, X. H., Li, F., Li, J., Sun, W. C., Wang, E. D., An, Y. P., Tang, H. R., Yan, G. Q., Yang, P. Y., Wei, Y., Mao, Y. Z., Lin, P. C., Zhao, J. Y., Xu, Y.*, Xu, W.*, and Zhao, S.* M. (2018) Sensing and Transmitting Intracellular Amino Acid Signals through Reversible Lysine Aminoacylations. Cell Metab 27, 151-166 e156 [Cover Story]
　　Preview: Aminoacylation of Proteins: New Targets for the Old ARSenal
　　2017
　　3.Yin, X., Liu, M., Tian, Y., Wang, J., and Xu, Y.* (2017) Cryo-EM structure of human DNA-P K holoenzyme. Cell research 27, 1341-1350
　　Highlights: Structural Stemp Forward for NHEJ. Cell Research 2017 Nov;27(11):1304-1306
　　2016
　　4.Yang, H., Wang, J., Liu, M., Chen, X., Huang, M., Tan, D., Dong, M. Q., Wong, C. C., Wang, J., Xu, Y.*, and Wang, H. W. (2016) 4.4 A Resolution Cryo-EM structure of human mTOR Complex 1. Protein & cell 7, 878-887
　　5.Yin, X., and Xu, Y.* (2016) Structure and Function of TET Enzymes. Adv Exp Med Biol 945, 275-302
　　6.Fang J, Cheng J, Wang J, Zhang Q, Liu M, Gong R, Wang P, Zhang X, Feng Y, Lan W, Wong J, Yang H, Cao C, Xu, Y.* Hemi-methylated DNA Opens a Closed Conformation of UHRF1 to Facilitate Its Histone Recognition. Nat Commun. 7:11197.
　　7.Lu J, Hu L, Cheng J, Fang D, Wang C, Yu K, Jiang H, Cui Q, Xu Y*, Luo C* (2016) A computational investigation on the substrate preference of ten-eleven-translocation 2 (TET2). Phys Chem Chem Phys. 2016 Feb 3;18(6):4728-38

kyone

　　2015
　　8.Hu L, Lu J, Cheng J, Rao Q, Li Z, Hou H, Lou Z, Zhang L, Li W, Gong W, Liu M, Sun C, Yin X, Li J, Tan X, Wang P, Wang Y, Fang D, Cui Q, Yang P, He C, Jiang H, Luo C*, Xu, Y.* Structural insight into substrate preference for TET-mediated oxidation. Nature. 2015 Nov 5;527:118-22.
　　9.Cheng J, Li Z, Gong R, Fang J, Yang Y, Sun C, Yang H, Xu Y.* Molecular mechanism for the substrate recognition of USP7. Protein Cell. 2015 Nov;6(11):849-52.
　　10.Gong R, Hong AW, Plouffe SW, Zhao B, Liu G, Yu FX*, Xu Y.*, Guan KL*. (2015) Opposing roles of conventional and novel P KC isoforms in Hippo-YAP pathway regulation. Cell research 25(8):985-8
　　11.Cheng J, Yang H, Fang J, Ma L, Gong R, Wang P, Li Z, Xu Y.* (2015) Molecular mechanism for USP7-mediated DNMT1 stabilization by acetylation. Nat Commun. 6:7023
　　12Wang P, Sun C, Zhu T, Xu, Y.* (2015)Structural insight into mechanisms for dynamic regulation of P KM2. Protein Cell 6(4):275-87 (封面故事)
　　Highlights：Protein & Cell
　　13.Yang Y, Yin X, Yang H, Xu, Y.* (2015) Histone Demethylase LSD2 Acts as an E3 Ubiquitin Ligase and Inhibits Cancer Cell Growth through Promoting Proteasomal Degradation of OGT. Molecular cell 58, 47-59
　　Highlights：Science Signaling
　　14.Guo, X., Wang, L., Li, J., Ding, Z., Xiao, J., Yin, X., He, S., Shi, P., Dong, L., Li, G., Tian, C., Wang, J., Cong, Y., and Xu, Y.* (2015) Structural insight into autoinhibition and histone H3-induced activation of DNMT3A. Nature 517, 640-644
　　Highlights：Faculty of 1000
　　2014
　　15.Zhu, T., Roundtree, I. A., Wang, P., Wang, X., Wang, L., Sun, C., Tian, Y., Li, J., He, C., and Xu, Y.* (2014) Crystal structure of the YTH domain of YTHDF2 reveals mechanism for recognition of N6-methyladenosine. Cell research 24, 1493-1496
　　16.Zhang, Y., Yang, H., Guo, X., Rong, N., Song, Y., Xu, Y., Lan, W., Zhang, X., Liu, M., Xu, Y.*, and Cao, C.* (2014) The PHD1 finger of KDM5B recognizes unmodified H3K4 during the demethylation of histone H3K4me2/3 by KDM5B. Protein & cell 5, 837-850
　　2013
　　17.Hu, L.#, Li, Z. #, Cheng, J. #, Rao, Q., Gong, W., Liu, M., Shi, YG., Zhu, J., Wang, P. and Xu, Y. * (2013) Crystal Structure of TET2-DNA Complex: Insight into TET-Mediated 5mC Oxidation, Cell155, 1545-1555
　　Highlights：Faculty of 1000, Nature China, Preview in Cell
　　18.Yang, H. #, Gong, R. #, and Xu, Y.* (2013) Control of cell growth: Rag GTPases in activation of TORC1, Cellular and molecular life sciences : CMLS70, 2873-2885. [review]
　　19.Fang, R. #, Chen, F. #, Dong, Z., Hu, D., Barbera, A. J., Clark, E. A., Fang, J., Yang, Y., Mei, P., Rutenberg, M., Li, Z., Zhang, Y., Xu, Y., Yang, H., Wang, P., Simon, M. D., Zhou, Q., Li, J., Marynick, M. P., Li, X., Lu, H., Kaiser, U. B., Kingston, R. E., Xu, Y.*, and Shi, Y. G.* (2013) LSD2/KDM1B and its cofactor NPAC/GLYR1 endow a structural and molecular model for regulation of H3K4 demethylation, Molecular cell 49, 558-570.
　　Highlights：Nature China
　　20.Chen, F. #, Yang, H. #, Dong, Z. #, Fang, J., Wang, P., Zhu, T., Gong, W., Fang, R., Shi, Y. G., Li, Z.*, and Xu, Y.* (2013) Structural insight into substrate recognition by histone demethylase LSD2/KDM1b, Cell research 23, 306-309.
　　21.Cheng, J., Yang, Y., Fang, J., Xiao, J., Zhu, T., Chen, F., Wang, P., Li, Z., Yang, H., and Xu, Y.* (2013) Structural insight into coordinated recognition of trimethylated histone H3 lysine 9 (H3K9me3) by the plant homeodomain (PHD) and tandem tudor domain (TTD) of UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) protein, The Journal of biological chemistry 288, 1329-1339.
　　22.Zhao, D., Zou, S. W., Liu, Y., Zhou, X., Mo, Y., Wang, P., Xu, Y., Dong, B., Xiong, Y., Lei, Q. Y., and Guan, K. L. (2013) Lysine-5 acetylation negatively regulates lactate dehydrogenase A and is decreased in pancreatic cancer, Cancer cell 23, 464-476.
　　23.Huang, W., Jiang, T., Choi, W., Qi, S., Pang, Y., Hu, Q., Xu, Y., Gong, X., Jeffrey, P. D., Wang, J., and Shi, Y. (2013) Mechanistic insights into CED-4-mediated activation of CED-3, Genes & development 27, 2039-2048.
　　2012
　　24.Ma, H. #, Chen, H. #, Guo, X. #, Wang, Z., Sowa, M. E., Zheng, L., Hu, S., Zeng, P., Guo, R., Diao, J., Lan, F., Harper, J. W., Shi, Y. G., Xu, Y.*, and Shi, Y.* (2012) M phase phosphorylation of the epigenetic regulator UHRF1 regulates its physical association with the deubiquitylase USP7 and stability, Proceedings of the National Academy of Sciences of the United States of America 109, 4828-4833.
　　25.Xiao, M., Yang, H., Xu, W., Ma, S., Lin, H., Zhu, H., Liu, L., Liu, Y., Yang, C., Xu, Y., Zhao, S., Ye, D., Xiong, Y., and Guan, K. L. (2012) Inhibition of alpha-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors, Genes & development 26, 1326-1338.
　　2011
　　26.Gong, R. #, Li, L. #, Liu, Y. #, Wang, P., Yang, H., Wang, L., Cheng, J., Guan, K. L., and Xu, Y.* (2011) Crystal structure of the Gtr1p-Gtr2p complex reveals new insights into the amino acid-induced TORC1 activation, Genes & development 25, 1668-1673.
　　27.Hu, L. #, Li, Z. #, Wang, P., Lin, Y., and Xu, Y.*(2011) Crystal structure of PHD domain of UHRF1 and insights into recognition of unmodified histone H3 arginine residue 2, Cell research 21(9):1374-8
　　28.Jeong, B. R. #, Lin, Y. #, Joe, A., Guo, M., Korneli, C., Yang, H., Wang, P., Yu, M., Cerny, R. L., Staiger, D., Alfano, J. R.*, and Xu, Y.*(2011) Structure function analysis of an ADP-ribosyltransferase type III effector and its RNA-binding target in plant immunity, The Journal of biological chemistry 286, 43272-43281.
　　29.Xu, W.#, Yang, H.#, Liu, Y.#, Yang, Y., Wang, P., Kim, S. H., Ito, S., Yang, C., Wang, P., Xiao, M. T., Liu, L. X., Jiang, W. Q., Liu, J., Zhang, J. Y., Wang, B., Frye, S., Zhang, Y., Xu, Y., Lei, Q. Y., Guan, K. L., Zhao, S. M., and Xiong, Y. (2011) Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases, Cancer cell 19, 17-30.
　　30.Rajakumara, E.#, Wang, Z.#, Ma, H., Hu, L., Chen, H., Lin, Y., Guo, R., Wu, F., Li, H., Lan, F., Shi, Y. G., Xu, Y., Patel, D. J., and Shi, Y. (2011) PHD Finger Recognition of Unmodified Histone H3R2 Links UHRF1 to Regulation of Euchromatic Gene Expression, Molecular cell 43, 275-284.
　　31.Guo, X.#, Xu, Y. #, Wang, P., Li, Z., Xu, Y.*, and Yang, H.* (2011) Crystallization and preliminary crystallographic analysis of a PHD domain of human JARID1B, Acta crystallographica 67, 907-910.
　　2010
　　32.Li, Z. #, Zhao, B. #, Wang, P., Chen, F., Dong, Z., Yang, H., Guan, K. L.*, and Xu, Y.* (2010) Structural insights into the YAP and TEAD complex, Genes & development 24, 235-240.
　　33.Yang, Y. #, Hu, L. #, Wang, P. #, Hou, H., Lin, Y., Liu, Y., Li, Z., Gong, R., Feng, X., Zhou, L., Zhang, W., Dong, Y., Yang, H., Lin, H., Wang, Y., Chen, C. D.*, and Xu, Y.* (2010) Structural insights into a dual-specificity histone demethylase ceKDM7A from Caenorhabditis elegans, Cell research 20, 886-898.
　　Highlights：Cell Research
　　34.Lin, H., Wang, Y., Wang, Y., Tian, F., Pu, P., Yu, Y., Mao, H., Yang, Y., Wang, P., Hu, L., Lin, Y., Liu, Y., Xu, Y.*, and Chen, C. D.* (2010) Coordinated regulation of active and repressive histone methylations by a dual-specificity histone demethylase ceKDM7A from Caenorhabditis elegans, Cell research 20, 899-907.
　　35.Yang, H. #, Wang, Z. #, Shen, Y.#, Wang, P., Jia, X., Zhao, L., Zhou, P., Gong, R., Li, Z., Yang, Y., Chen, D.*, Murchie, A. I.*, and Xu, Y.* (2010) Crystal structure of the nosiheptide-resistance methyltransferase of Streptomyces actuosus, Biochemistry 49, 6440-6450.
　　36.Yang, H.#, Wang, P.#, Dong, Z.#, Li, X., Gong, R., Yang, Y., Li, Z., Xu, Y., and Xu, Y.* (2010) Crystallization and preliminary crystallographic analysis of nosiheptide-resistance methyltransferase from Streptomyces actuosus in complex with SAM, Acta crystallographica 66, 579-582.
　　37.Lin, Y.#, Wang, P.#, Yang, H.*, and Xu, Y.* (2010) Crystallization and preliminary crystallographic analysis of the ADP-ribosyltransferase HopU1, Acta crystallographica 66, 932-934.
　　学术专著
　　申请或授权专利
　　授权专利
　　1. YAP-TEAD蛋白复合物的三维结构及其应用 发明创造 徐彦辉、李泽、管坤良 ZL 201010100934.4 2015.07.29
　　申请专利
　　1. TET2蛋白和5-mC DNA的三维结构及其应用 发明创造 徐彦辉 201310647635.6 2013.12.04