尚永丰,男,1964年6月生,汉族,甘肃省通渭县人。1986年毕业于甘肃农业大学兽医系;1989年毕业于中国兽药监察所,获硕士学位; 1999年毕业于美国宾夕法尼亚州立大学,获博士学位。1999年至2002年在美国哈佛大学进行博士后工作。2009年当选为中国科学院生命科学和医学学部院士。现为北京大学基础医学院生物化学与分子生物学系教授(2002年)、系主任,长江学者(2002年)。
主要从事基因转录调控的表观遗传机制及性激素相关妇科肿瘤分子机理的研究。提出、验证并从分子机理上诠释了雌激素受体转录起始复合体在靶基因启动子上循环反复结合的假说以及雌激素受体所介导的基因转录具有“双相性”和“两维性”的特点,为基因转录调控的理论增添了新的内容;揭示了雌激素受体拮抗剂三苯氧胺诱发子宫内膜癌的分子机理,克隆了多个肿瘤相关基因,对肿瘤分子生物学的理论发展有重要意义;揭示了组蛋白去乙酰化和组蛋白去甲基化在染色质重塑中协调作用的机理,对认识表观遗传调控的分子机制具有创新性的理论意义;在世界上首次建立了哺乳动物细胞染色质免疫沉淀技术(ChIP),对DNA与蛋白质相互作用的研究做出了贡献。多年来在《Cell》、《Nature》和《Science》等杂志上发表了一系列的研究论文。
2006年获第九届“中国青年科技奖”、美国ELI Lilly公司的“礼来科研成就奖”;2007年获“中华医学科技奖”一等奖、“教育部自然科学奖”一等奖和“何梁何利科学与技术进步奖”;2008年获“国家自然科学奖”二等奖;指导的博士生获2007年度全国百篇优秀博士论文奖。
2004年起担任《中国生物化学与分子生物学学报》副主编,2007年被国际著名学术杂志《Journal of Biological Chemistry》聘为编委(Editorial Board)。
联系方式
Email:yshang@hsc.pku.edu.cn
实验室成员
教工:
王丹 副主任技师 wd@bjmu.edu.cn
吴歌 助理 wuge@bjmu.edu.cn
中国科学院院士
研究方向与领域
主要研究方向:基因转录调控的表观遗传机制和乳腺癌/子宫内膜癌发生发展的分子机理。
多年来,在《Cell》、《Nature》、《Science》、《Nature Genetics》、《Cancer Cell》、《Molecular Cell》、《Genes & Development》、《The Journal of Clinical Investigation》等发表一系列高影响论文。其中2002年发表于《Cell》的关于雌激素受体转录复合体循环作用于基因启动子的论文被同行认为是经典和代表之作。2005年在《Nature》发表论文,阐明了为什么三苯氧胺能有效治疗乳腺癌而又能导致子宫内膜癌这一长期倍受公众和科学界关注的重要问题,为子宫内膜癌的治疗和预防提供了新的思路和药物靶点,同时也对肿瘤分子生物学的理论发展做出了贡献。2009年在《Cell》发表研究论文,揭示了乳腺癌转移的表观遗传机制,对认识表观遗传调控的机理有着开创性的理论意义。2016年在《Nature Genetics》发表论文,将先锋因子FOXA1的先锋活性与表观遗传调控紧密联系起来。尚院士曾受邀为《Nature Reviews Cancer》和《Annual Review of Physiology》等撰写综述,其研究工作曾获“中国基础研究十大新闻”、“中国高等学校十大科技进展”、“中华医学科技奖”一等奖、“教育部自然科学”一等奖、并两次(2008、2016)获得“国家自然科学奖”二等奖。尚院士还曾获Eli Lilly“礼来科研成就奖”、“何梁何利科学与技术进步奖”、“药明康德生命化学研究奖”一等奖和树兰医学奖;指导的博士生论文在2007和2011年两度获评“全国百篇优秀博士学位论文”。
主要代表作
(1)Yazi Yang #, Sen Qin #, Mengyu Yang, Ting Wang, Ru Feng, Chunli Zhang, Enrun Zheng, Qinghua Li, Pengyu Xiang, ShangyongNing, Xiaodong Xu, Xin Zuo, Shuai Zhang, Xiaoya Yun, Xuehong Zhou, Yue Wang, Lin He, Yongfeng Shang*, Luyang Sun*, Hui Liu*(2024). Reconstitution of the Multiple Myeloma Microenvironment Following Lymphodepletion with BCMA CAR-T Therapy. Clinical Cancer Research.30(18):4201-4214.
(2)Xiao Cheng, Chunyu Yu, Yan Zhang, Yani Peng, Yuncheng Liu, Hangwei Fa, Lu Xia, Leyi Qin, Sudun Guan, Xiaodi Wu, Jiajing Wu, Yue Wang, Jianying Liu, Luyang Sun, Jing Liang*, and Yongfeng Shang*(2024). Loss of ZNF408 attenuates STING-mediated immune surveillance in breast carcinogenesis. iScience.27(7):110276.
(3)Wenting Zhang, Yue Wang, Yongjie Liu, Cuifang Liu, Yizhou Wang, Lin He, Xiao Cheng, Yani Peng, Lu Xia, Xiaodi Wu, Jiajing Wu, Yu Zhang, Luyang Sun, Ping Chen, Guohong Li, Qiang Tu, Jing Liang*, and Yongfeng Shang*(2023). NFIB facilitates replication licensing by acting as a genome organizer. Nature Communications. 14(1):5076.
(4)Yani Peng, Xiaoping Liu, Xinhua Liu, Xiao Cheng, Lu Xia, Leyi Qin, Sudun Guan, Yue Wang, Xiaodi Wu, Jiajing Wu, Dong Yan, Jianying Liu, Yu Zhang, Luyang Sun, Jing Liang* and Yongfeng Shang*(2023). RCCD1 promotes breast carcinogenesis through regulating hypoxia-associated mitochondrial homeostasis. Oncogene. 42(50):3684-3697.
(5)Xing Chen, Chunyu Yu, Xinhua Liu, Beibei Liu, Xiaodi Wu, Jiajing Wu, Dong Yan, Lulu Han, Zifan Tang, Xinyi Yuan, Jianqiu Wang, Yue Wang, Shumeng Liu, Lin Shan, Yongfeng Shang* (2022).Intracellular galectin-3 is a lipopolysaccharide sensor that promotes glycolysis through mTORC1 activation.Nature Communications.13(1):7578.
(6)Yue Wang, Yunchao Huang, Edith Cheng, Xinhua Liu, Yu Zhang, Jianguo Yang, Jordan T F Young, Grant W Brown, Xiaohan Yang*, Yongfeng Shang* (2022). LSD1 is required for euchromatic origin firing and replication timing.Signal Transduction and Targeted Therapy. 7(1):102.
(7)Beibei Liu,Xinhua Liu, Lulu Hana, Xing Chen, Xiaodi Wu, Jiajing Wu, Dong Yan, Yue Wang, Shumeng Liu, Lin Shana, Yu Zhang, and Yongfeng Shang* (2022). BRD4-directed super-enhancer organization of transcription repression programs links to chemotherapeutic efficacy in breast cancer.Proc Natl Acad Sci U S A.119(6):e2109133119.
(8)Xujun Liu, Wenzhe Si, Lin He, Jianguo Yang, Yani Peng, Jie Ren, Xiaoping Liu, Tong Jin, Huajing Yu, Zihan Zhang, Xiao Cheng, Wenting Zhang, Lu Xia, Yunchao Huang, Yue Wang, Shumeng Liu, Lin Shan, Yu Zhang, Xiaohan Yang, Haixia Li, Jing Liang, Luyang Sun* and Yongfeng Shang* (2021). The existence of a nonclassical TCA cycle in the nucleus thatwires the metabolic-epigenetic circuitry.Signal Transduction and Targeted Therapy. 6:375
(9)Zihan Zhang, Xiaoping Liu, Lei Li, Yang Yang, Jianguo Yang, Yue Wang, Jiajing Wu, Xiaodi Wu, Lin Shan, Fei Pei, Jianying Liu, Shu Wang, Wei Li, Luyang Sun , Jing Liang* and Yongfeng Shang* (2021). SNP rs4971059 predisposes to breast carcinogenesis and chemoresistance via TRIM46-mediated HDAC1 degradation.The EMBO Journal. 40: e107974
(10)Xiaoping Liu, Bosen Xu, Jianguo Yang, Lin He, Zihan Zhang, Xiao Cheng, Huajing Yu, Xujun Liu, Tong Jin, Yani Peng, Yunchao Huang, Lu Xia, Yue Wang, Jiajing Wu, Xiaodi Wu, Shumeng Liu, Lin Shan, Xiaohan Yang, Luyang Sun, Jing Liang, Yu Zhang* and Yongfeng Shang* (2021). UHRF2 commissions the completion of DNA demethylation through allosteric activation by 5hmC and K33-linked ubiquitination of XRCC1. Molecular Cell. 81: 1-15
(11)Jianguo Yang, Xiaoping Liu, Yunchao Huang, Lin He, Wenting Zhang, Jie Ren, Yue Wang, Jiajing Wu, Xiaodi Wu, Lin Shan, Xiaohan Yang, Luyang Sun, Jing Liang, Yu Zhang*, and Yongfeng Shang* (2021). TRPS1 drives heterochromatic origin refiring and cancer genome evolution. Cell Reports. 34: 108814
(12)Chao Yang, Jiajing Wu, Xinhua Liu, Yue Wang, Beibei Liu, Xing Chen, Xiaodi Wu, Dong Yan, Lulu Han,Shumeng Liu,Lin Shan,and Yongfeng Shang* (2020). Circadian rhythm is disrupted by ZNF704 in breast carcinogenesis. Cancer Research 80(19):4114-4128
(13)Lin He, Xinhua Liu, Jianguo Yang, Wanjin Li, Shumeng Liu, Xujun Liu, Ziran Yang, JieRen, Yue Wang, Lin Shan, Chengjian Guan, Fei Pei, Liandi Lei, Yu Zhang, Xia Yi, Xiaohan Yang, Jing Liang, Rong Liu, Luyang Sun* and Yongfeng Shang* (2018). Imbalance of the reciprocally inhibitory loop between the ubiquitin-specific protease USP43 and EGFR/PI3K/AKT drives breast carcinogenesis. Cell Research 28: 934–951
(14)Shumeng Liu, Huajing Yu, Yongqing Liu, Xinhua Liu, Yu Zhang, Chen Bu, Shuai Yuan, Zhe Chen, GuojiaXie, Wanjin Li, BosenXu, Jianguo Yang, Lin He, Tong Jin, YundongXiong, Luyang Sun, Xiaohui Liu, Chunsheng Han, Zhongyi Cheng, Jing Liang*, and Yongfeng Shang* (2017). Chromodomainprotein CDYL acts as a crotonyl-CoA hydratase to regulate histone crotonylation and spermatogenesis. Molecular Cell 67: 853-866
(15)Wanjin Li, Zihan Zhang, Xinhua Liu, Xiao Cheng, Yi Zhang, Xiao Han, Yu Zhang, Shumeng Liu, Jianguo Yang, Bosen Xu, Lin He, Luyang Sun, Jing Liang, and Yongfeng Shang* (2017). The FOXN3-NEAT1-SIN3A repressor complex promotes progression of hormonally responsive breast cancer. The Journal of Clinical Investigation 127: 3421-3440
(16)Xin Li, Nan Song, Ling Liu, Xinhua Liu, Xiang Ding, Xin Song, Shangda Yang, Lin Shan, Xing Zhou, Dongxue Su, Yue Wang, Qi Zhang, Cheng Cao, Shuai Ma, Na Yu, Fuquan Yang, Yan Wang, Zhi Yao, Yongfeng Shang*, and Lei Shi* (2017). USP9X regulates centrosome duplication and promotes breast carcinogenesis. Nature Communications 8:14866/ DOI: 10.1038/ncomms14866
(17)Yu Zhang, Di Zhang, Qian Li, Jing Liang, Luyang Sun, Xia Yi, Zhe Chen, Ruorong Yan, GuojiaXie, Wanjin Li, Shumeng Liu, BosenXu, Lei Li, Jianguo Yang, Lin He, and Yongfeng Shang* (2016). Nucleation of DNA repair factors by FOXA1 links DNA demethylation to transcriptional pioneering. Nature Genetics 48:1003-1013
(18)Lin Shan, Xing Zhou, Xinhua Liu, Yue Wang, Dongxue Su, YongqiangHou, Na Yu, Chao Yang, Beibei Liu, JieGao, Yang Duan, Jianguo Yang, Wanjin Li, Jing Liang, Luyang Sun, Kexin Chen, ChenghaoXuan, Lei Shi, Yan Wang, Yongfeng Shang* (2016). FOXK2 elicits massive transcription repression and suppresses the hypoxic response and breast cancer carcinogenesis. Cancer Cell 30: 708-722
(19)Lei Li, Lan Shi, Shangda Yang, Ruorong Yan, Di Zhang, Jianguo Yang, Lin He, Wanjin Li, Xia Yi, Luyang Sun, Jing Liang, Zhongyi Cheng, Lei Shi, Yongfeng Shang*, and Wenhua Yu* (2016). SIRT7 is a histone desuccinylase that functionally links to chromatin compaction and genome stability. Nature Communications 7:12235/DOI: 10.1038/ncomms12235
(20)Yang Duan, Dawei Huo, Jie Gao, Heng Wu, Zheng Ye, Zhe Liu, Kai Zhang, Lin Shan, Xing Zhou, Yue Wang, Dongxue Su, Xiang Ding, Lei Shi, Yan Wang, Yongfeng Shang*, and Chenghao Xuan* (2016). Ubiquitin ligase RNF20/40 facilitates spindle assembly and promotes breast carcinogenesis through stabilizing motor protein Eg5. Nature Communications 7:12648/DOI: 10.1038/ncomms12648
(21)Wenzhe Si, Wei Huang, Yu Zheng, Yang Yang, Xujun Liu, Lin Shan, Xing Zhou, Yue Wang, Dongxue Su, Jie Gao, Ruorong Yan, Xiao Han, Wanjin Li, Lin He, Lei Shi, Chenghao Xuan, Jing Liang, Luyang Sun, Yan Wang*, and Yongfeng Shang* (2015). Dysfunction of the reciprocal feedback loop between GATA3- and ZEB2-Nucleated repression programs contributes to breast cancer metastasis. Cancer Cell 27: 822–836
(22)Ruorong Yan, Lin He, Zhongwu Li, Xiao Han, Jing Liang, Wenzhe Si, Zhe Chen, Lei Li, Guojia Xie, Wanjin Li, Peiyan Wang, Liandi Lei, Hongquan Zhang, Fei Pei, Dengfeng Cao, Luyang Sun*, and Yongfeng Shang* (2015). SCFJFK is a bona fide E3 ligase for ING4 and a potent promoter of the angiogenesis and metastasis of breast cancer. Genes & Development 29: 672-685
(23)Xiao Han, Bin Gui, Cong Xiong, Linnan Zhao, Jing Liang, Luyang Sun, Xiaohan Yang, Wenhua Yu, Wenzhe Si, Ruorong Yan, Xia Yi, Di Zhang, Wanjin Li, Lifang Li, Jianguo Yang, Yan Wang, Yi Eve Sun, Dai Zhang, Anming Meng, and Yongfeng Shang* (2014). Destabilizing LSD1 by Jade-2 promotes neurogenesis: an anti-braking system in neural development. Molecular Cell 55: 482–494
(24)Feng Wang, Lin He, Peiwei Huangyang, Jing Liang, Wenzhe Si, Ruorong Yan, Xiao Han, Shumeng Liu, Bin Gui, Wanjin Li, Di Miao, Chao Jing, Zhihua Liu, Fei Pei, Luyang Sun*, Yongfeng Shang* (2014) JMJD6 promotes colon carcinogenesis through negative regulation of p53 by hydroxylation. PLoS Biology 12(3): e1001819. doi:10.1371/ journal.pbio.1001819
(25)Jing Liang, Yongfeng Shang* (2013). Estrogen and cancer. Annual Review of Physiology 75: 225-40
(26)Xiaohan Yang, Wenhua Yu, Lei Shi, Luyang Sun, Jing Liang, Xia Yi, Qian Li, Yu Zhang, Fen Yang, Xiao Han, Di Zhang, Jie Yang, Zhi Yao, and Yongfeng Shang* (2011). HAT4, a Golgi apparatus-anchored B-type histone acetyltransferase, acetylates free histone H4 and facilitates chromatin assembly. Molecular Cell 44: 39-50
(27)Yan Wang, Hua Zhang, Yupeng Chen, Yimin Sun, Fen Yang, Wenhua Yu, Jing Liang, Luyang Sun, Xiaohan Yang, Lei Shi, Ruifang Li, Qian Li, Xia Yi, and Yongfeng Shang* (2009). LSD1 is a subunit of the NuRD complex and targets the metastasis programmes in breast cancer. Cell 138: 660-672
(28)Yongfeng Shang* (2006). Molecular mechanisms of oestrogen and SERMs in endometrial carcinogenesis. Nature Reviews Cancer 6: 360-368 (invited review)
(29)Huijian Wu, Yupeng Chen, Jing Liang, Bin Shi, Ge Wu, Ying Zhang, Dan Wang, Ruifang Li, Xia Yi, Hua Zhang, Luyang Sun, and Yongfeng Shang* (2005). Hypomethylation-linked activation of PAX2 mediates tamoxifen-stimulated endometrial carcinogenesis. Nature 438: 981-987
(30)Hua Zhang, Xia Yi, Xiaojing Sun, Na Yin, Bin Shi, Huijian Wu, Dan Wang, Ge Wu, and Yongfeng Shang* (2004). Differential gene regulation by the SRC family of coactivators. Genes and Development 18: 1753-1765
(31)Yongfeng Shang and Myles Brown (2002). Molecular determinants for the tissue specificity of SERMs. Science 295: 2465-2468
(32)Yongfeng Shang, Xiao Hu, James Direnzo, Mitch Lazar, and Myles Brown (2000). Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription. Cell 103: 843-852


