博士,研究员,博士生导师,复旦大学附属肿瘤医院研究员,生物医学研究院兼职研究员
地址:东安路131号,明道楼715室,上海 200032
电话:021-54237880(实验室)
邮箱:xuyh@fudan.edu.cn 、xulab@foxmail.com
实验室主页:http://xulab.fudan.edu.cn
实验室在2023年开始,做了较大的研究方向调整。1. 在结构生物学方向,继续开展转录起始的机制研究,将研究体系拓展至多聚核小体模板上的转录起始复合物的静态结构,转录起始的动态过程,并拓展研究方法,包括体外生化分析,利用测序技术表征转录起始过程,单分子生物物理方法研究转录起始的动态过程等。希望综合利用结构生物学、生物化学、生物物理等方法,系统的阐释转录起始这一极其复杂且重要的生物学过程。2. 我们在构建蛋白质抗体库作为独特的研究工具,开发同时靶向多种蛋白质的测序新方法,在单细胞、发育、病理等层面解析生物大分子在细胞层面的复杂相互作用和功能,所取得的发现不仅可以指导深入的分子生物学研究,研究体系也可应用在基础研究和临床诊治等众多方面。我们认为这是生命科学研究长期未能解决的难题,是重大的机遇,也是课题组未来若干年重点发展的方向,我们有决心投入最大的热情和耐力实现这一目标。期待不同学术背景,有志于开展创新性研究的科学家与我们同行,我们会提供有竞争力的待遇。
徐彦辉,博士,研究员。本科和博士都在清华大学生物科学与技术系完成,2004年去普林斯顿大学做博后研究,2008年开始先后在复旦大学生物医学研究院和复旦大学附属肿瘤医院工作。长期从事基因表达调控的研究,围绕基因启动子区发生的转录起始复合物装配,染色质重塑和DNA甲基化调控,系统揭示了基因表达调控的分子机制,成果得到国内外同行高度评价。发表通讯作者论文40余篇,包括5篇Science,2篇Nature,1篇Cell,5篇 Nature Communications, 13篇Cell research等。曾获新基石研究员项目(腾讯基金会)、国家杰出青年科学基金(基金委)等人才项目,曾获科学探索奖、谈家桢生命科学奖(创新奖)、中国优秀青年科技人才奖等荣誉。曾主持国家重点研发计划2项(项目负责人),国家自然科学基金重点项目4项。部分成果获得教育部“高等学校科学研究优秀成果奖自然科学一等奖”(第一完成人)、2021年度“中国生命科学十大进展”、中国2021医学重要进展。
*通讯作者,# 共同第一作者(更新请见https://xulab.fudan.edu.cn/Publications.htm)
Transcription
1.Chen, X., Wang, X., Liu, W., Ren, Y., Qu, X., Li, J., Yin, X., and Xu, Y.* (2022) Structures of +1 nucleosome-bound PIC-Mediator complex. Science378, 62-68
2.Chen, X., Yin, X., Li, J., Wu, Z., Qi, Y., Wang, X., Liu, W., and Xu, Y.* (2021) Structures of the human Mediator and Mediator-bound preinitiation complex. Science 372, eabg0635
3.Chen, X., Qi, Y., Wu, Z., Wang, X., Li, J., Zhao, D., Hou, H., Li, Y., Yu, Z., Liu, W., Wang, M., Ren, Y., Li, Z., Yang, H., and Xu, Y.* (2021) Structural insights into preinitiation complex assembly on core promoters. Science 372, eaba8490
4.Zheng, H., Qi, Y., Hu, S., Cao, X., Xu, C., Yin, Z., Chen, X., Li, Y., Liu, W., Li, J., Wang, J., Wei, G., Liang, K., Chen, F. X.*, and Xu, Y.* (2020) Identification of Integrator-PP2A complex (INTAC), an RNA polymerase II phosphatase. Science 370, eabb5872
5.He, S., Wu, Z., Tian, Y., Yu, Z., Yu, J., Wang, X., Li, J., Liu, B., and Xu, Y.* (2020) Structure of nucleosome-bound human BAF complex. Science 367, 875-881
6.Chen, X., and Xu, Y.* (2022) Structural insights into assembly of transcription preinitiation complex. Curr Opin Struct Biol 75, 102404 (Review)
7.Zheng, H., Jin, Q., Wang, X., Qi, Y., Liu, W., Ren, Y., Zhao, D., Xavier Chen, F., Cheng, J., Chen, X., and Xu, Y.* (2023) Structural basis of INTAC-regulated transcription. Protein Cell
8.Hou, H., Jin, Q., Ren, Y., Chen, Z., Wang, Q., and Xu, Y.* (2023) Structure of the SNAPc-bound RNA polymerase III preinitiation complex. Cell Res
9.Wang, X., Qi, Y., Wang, Z., Wang, L., Song, A., Tao, B., Li, J., Zhao, D., Zhang, H., Jin, Q., Jiang, Y. Z., Chen, F. X.*, Xu, Y.*, and Chen, X.* (2022) RPAP2 regulates a transcription initiation checkpoint by inhibiting assembly of pre-initiation complex. Cell Rep39, 110732
10.Zhao, D., Liu, W., Chen, K., Wu, Z., Yang, H., and Xu, Y.* (2021) Structure of the human RNA polymerase I elongation complex. Cell Discov 7, 97
11.Hou, H., Li, Y., Wang, M., Liu, A., Yu, Z., Chen, K., Zhao, D., and Xu, Y.* (2021) Structural insights into RNA polymerase III-mediated transcription termination through trapping poly-deoxythymidine. Nat Commun 12, 6135
12.Li, L., Yu, Z., Zhao, D., Ren, Y., Hou, H., and Xu, Y.* (2021) Structure of human RNA polymerase III elongation complex. Cell Res 31, 791-800
13.Feng, Y., Tian, Y., Wu, Z., and Xu, Y.* (2018) Cryo-EM structure of human SRCAP complex. Cell Res 28, 1121-1123
Epigenetics
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
15.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.*, and Xu, Y.* (2015) Structural insight into substrate preference for TET-mediated oxidation. Nature 527, 118-122
16.Hu, L., Li, Z., Cheng, J., Rao, Q., Gong, W., Liu, M., Shi, Y. G., Zhu, J., Wang, P., and Xu, Y.* (2013) Crystal structure of TET2-DNA complex: insight into TET-mediated 5mC oxidation. Cell 155, 1545-1555
17.Yang, Y., Yin, X., Yang, H., and Xu, Y.* (2015) Histone demethylase LSD2 acts as an E3 ubiquitin ligase and inhibits cancer cell growth through promoting proteasomal degradation of OGT. Mol Cell 58, 47-59
18.Yang, H., Yu, Z., Chen, X., Li, J., Li, N., Cheng, J., Gao, N., Yuan, H. X., Ye, D., Guan, K. L., and Xu, Y.* (2021) Structural insights into TSC complex assembly and GAP activity on Rheb. Nat Commun 12, 339
19.Fang, J., Cheng, J., Wang, J., Zhang, Q., Liu, M., Gong, R., Wang, P., Zhang, X., Feng, Y., Lan, W., Gong, Z., Tang, C., Wong, J., Yang, H., Cao, C., and Xu, Y.* (2016) Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition. Nat Commun 7, 11197
20.Cheng, J., Yang, H., Fang, J., Ma, L., Gong, R., Wang, P., Li, Z., and Xu, Y.* (2015) Molecular mechanism for USP7-mediated DNMT1 stabilization by acetylation. Nat Commun 6, 7023
21.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 Res 24, 1493-1496
22.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 Res 23, 306-309
23.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 Res 21, 1374-1378
24.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 Res 20, 886-898
25.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. J Biol Chem 288, 1329-1339
26.Cheng, J., Li, Z., Gong, R., Fang, J., Yang, Y., Sun, C., Yang, H., and Xu, Y.* (2015) Molecular mechanism for the substrate recognition of USP7. Protein Cell 6, 849-852
27.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
28.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. Mol Cell 49, 558-570
29.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. Proc Natl Acad Sci U S A 109, 4828-4833
30.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 Res 20, 899-907
DNA damage response and cancer pathway
31.Xiao, J., Liu, M., Qi, Y., Chaban, Y., Gao, C., Pan, B., Tian, Y., Yu, Z., Li, J., Zhang, P., and Xu, Y.* (2019) Structural insights into the activation of ATM kinase. Cell Res 29, 683-685
32.Zhu, L., Li, L., Qi, Y., Yu, Z., and Xu, Y.* (2019) Cryo-EM structure of SMG1-SMG8-SMG9 complex. Cell Res 29, 1027-1034
33.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 Res 28, 143-156
34.Yin, X., Liu, M., Tian, Y., Wang, J., and Xu, Y.* (2017) Cryo-EM structure of human DNA-PK holoenzyme. Cell Res 27, 1341-1350
35.Chen, X., Liu, M., Tian, Y., Li, J., Qi, Y., Zhao, D., Wu, Z., Huang, M., Wong, C. C. L., Wang, H. W., Wang, J., Yang, H.*, and Xu, Y.* (2018) Cryo-EM structure of human mTOR complex 2. Cell Res 28, 518-528
36.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
37.Pan, B., Yang, Y., Li, J., Wang, Y., Fang, C., Yu, F. X.*, and Xu, Y.* (2020) USP47-mediated deubiquitination and stabilization of YAP contributes to the progression of colorectal cancer. Protein Cell 11, 138-143
38.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 Dev 24, 235-240
39.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 Dev 25, 1668-1673
40.Wang, P., Sun, C., Zhu, T., and Xu, Y.* (2015) Structural insight into mechanisms for dynamic regulation of PKM2. Protein Cell 6, 275-287
41.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
42.Gong, R., Hong, A. W., Plouffe, S. W., Zhao, B., Liu, G., Yu, F. X.*, Xu, Y.*, and Guan, K. L.* (2015) Opposing roles of conventional and novel PKC isoforms in Hippo-YAP pathway regulation. Cell Res 25, 985-988