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  • 叶丹

    博士,研究员,博士生导师
    地址:东安路131号,科研二号楼A座3楼
    电话:021-54237834 (办公室)
    传真:021-54237450
    邮箱:yedan@fudan.edu.cn
    实验室主页:https://fudan-mcb.com

工作经历
研究员,复旦大学,生物医学研究院(2014.12-今)
副研究员,复旦大学,生物医学研究院(2011.3-2014.12)
博士后,荷兰莱顿大学(2008.9-2010.12)
教育经历
博士,荷兰莱顿大学,生物制药系(2004-2008)
硕士,浙江大学,遗传学系(2002-2004)
学士,浙江大学,生物技术(1998-2002)
所获人才项目
国家自然科学基金优秀青年基金,2015
青年启明星计划,上海市科委,2014
研究方向

代谢与表观遗传重塑是肿瘤重要特征,代谢酶和表观修饰酶也因此成为备受关注的抗肿瘤治疗靶点。近一半新发现的癌驱动因子是表观修饰酶,其中TET双加氧酶介导DNA主动去甲基化,是重要的肿瘤抑制因子。既往的研究大多关注代谢物提供肿瘤所需能量物质,而代谢物是否参与真核生物表观遗传和基因转录调控,不甚明确。事实上,几乎所有表观修饰酶都以代谢物为底物或辅因子。但由于代谢物具种类繁多、组织/细胞/亚细胞浓度差异大、响应环境刺激时动态变化等特点,代谢物调控表观遗传及失调促癌研究尚处于认知的初期阶段。叶丹及团队一直致力于研究代谢异常和表观遗传失调的肿瘤生物学意义,发现了代谢物作为信号分子调控TET等表观修饰酶活性,揭示了转录因子招募表观修饰酶来调控基因表达和代谢重塑等,阐释了肿瘤代谢物影响细胞恶性表型、肿瘤相关巨噬细胞极化和微环境重塑。

迄今,以第一或通讯作者在国际知名期刊发表SCI论文27篇。其中, 22篇为通讯作者(含共同)论文,刊登在Nat Cell Biol、Journal of Hepatology、Mol cell、Cell Res、Sci Adv、Genes Dev、EMBO J (2篇)、Cancer Res、Cell Rep (3篇)、EMBO Rep (2篇) 等。总他引3015次(2篇ESI高被引论文)。成果被Cancer Discov、Mol Cell、EMBO J、PLoS Biol等期刊专评。以第一或共同通讯作者在Nature、Cancer Cell等发表述评和综述4篇,并多次担任Nature、Cancer Cell、Nat Cell Biol等审稿人。在全球华人生物学家大会、中国细胞生物学学会等国际学术会议做大会及分会报告。现任中国抗癌协会肿瘤代谢专业委员会全国常委

代表论文

1.Renqiang Sun, Zhiyong Zhang, Ruoxuan Bao, Xiaozhen Guo, Yuan Gu, Wenjing Yang, Jinsong Wei, Xinyu Chen, Lingfeng Tong, Jian Meng, Chen Zhong, Cheng Zhang, Jinye Zhang, Yiping Sun, Chen Ling, Xuemei Tong, Fa-Xing Yu, Hongxiu Yu, Weifeng Qu, Bing Zhao, Wei Guo, Maoxiang Qian, Hexige Saiyin, Ying Liu, Rong-Hua Liu, Cen Xie, Weiren Liu, Yue Xiong, Kun-Liang Guan, Yinghong Shi, Pu Wang1,11, Dan Ye*. Loss of SIRT5 promotes bile acid-induced immunosuppressive microenvironment and hepatocarcinogenesis. Journal of Hepatology. 2022; In press.

2.Lei-Lei Chen#, Carmen Morcelle#, Zhou-Li Cheng#, Xiufei Chen, Yanping Xu, Yajing Gao, Junbin Song, Zhijun Li, Matthew D. Smith, Miao Shi, Yezhang Zhu, Neng Zhou, Meng Cheng, Chenxi He, Kwei-Yan Liu, Guoping Lu, Lei Zhang, Chen Zhang, Jingye Zhang, Yiping Sun, Tuan Qi, Yingying Lyu, Zhi-Zhong Ren, Xian-Ming Tan, Jiayong Yin, Fei Lan, Ying Liu, Hui Yang, Maoxiang Qian, Caiwen Duan, Xing Chang, Yufeng Zhou, Li Shen, Albert S. Baldwin, Kun-Liang Guan, Yue Xiong, and Dan Ye.* Itaconate Inhibits TET DNA Dioxygenases to Dampen Inflammatory Responses. Nature Cell Biology. 2022; In press.

3.Xiufei Chen#, Wenjie Zhou#, Ren-Hua Song#, Shuang Liu#, Shu Wang, Yujia Chen, Chao Gao, Chenxi He, Jianxiong Xiao, Lei Zhang, Tianxiang Wang, Peng Liu, Kunlong Duan, Zhouli Cheng, Chen Zhang, Jinye Zhang, Yiping Sun, Felix Jackson, Fei Lan, Yun Liu, Yanhui Xu, Justin Jong-Leong Wong, Pu Wang, Hui Yang, Yue Xiong, Tong Chen*, Yan Li*, Dan Ye.* Tumor suppressor CEBPA interacts with and inhibits DNMT3A activity. Science Advances. 2022; In press.

4.Cheng ZL, Zhang ML, Lin HP, Gao C, Song JB, Zheng Z, Li L, Zhang Y, Shen X, Zhang H, Huang Z, Zhan W, Zhang C, Hu X, Sun YP, Jiang L, Sun L, Xu Y, Yang C, Ge Y, Zhao Y, Liu X, Yang H, Liu P, Guo X, Guan KL, Xiong Y, Zhang M*, Ye D*.The Zscan4-Tet2 Transcription Nexus Regulates Metabolic Rewiring and Enhances Proteostasis to Promote Reprogramming.Cell Reports. 2020;32(2):107877.

5.Lei-Lei Chen#, Huai-Peng Lin#, Wen-Jie Zhou, Chen-Xi He, Zhi-Yong Zhang, Zhou-Li Cheng, Jun-Bin Song, Peng Liu, Xin-Yu Chen, Yu-Kun Xia, Xiu-Fei Chen, Ren-Qiang Sun, Jing-Ye Zhang, Yi-Ping Sun, Lei Song, Bing-Jie Liu, Rui-Kai Du, Chen Ding, Fei Lan, Sheng-Lin Huang, Feng-Zhou, Su-Ling Liu, Yue Xiong*, Dan Ye*, and Kun-Liang Guan*.SNIP1 recruits TET2 to regulate c-MYC target genes and cellular DNA damage response. Cell Reports. 2018;25(6):1485-1500.

6.D Ye*, KL Guan, Y Xiong*. Metabolism, Activity, and Targeting of D-and L-2-Hydroxyglutarates. Trends in Cancer. 2018;4(2):151-165 (Invited review)

7.Huai-Peng Lin, Zhou-Li Cheng, Ruo-Yu He, Lei Song, Meng-Xin Tian, Lisha Zhou, Beezly S. Groh, Weiren Liu, Min-Biao Ji, Chen Ding, Ying-Hong Shi, Kun-Liang Guan*, Dan Ye*, and Yue Xiong*. Destabilization of fatty acid synthase by acetylation inhibits de novo lipogenesis and tumor cell growth. Cancer Research. 2016;76, 6924-36 

8.Ye D*, Xiong Y*. Cancer: Suffocation of gene expression. Nature. 2016;537(7618):42-43.

9.Wang P, Wu J, Ma S-H, Zhang L, Yao J, Hoadley KA, Wilkerson MD, Perou CM, Guan K-L*, Ye D*, Xiong Y. Oncometabolite D-2-Hydroxyglutarate Inhibits ALKBH DNA Repair Enzymes and Sensitizes IDH Mutant Cells to Alkylating Agents. Cell Reports. 2015;13(11):2353-61.

10.Wang S-W, Jiang B-W, Zhang T-F, Liu L-X, Wang Y, Wang Y-P, Chen X-F, Lin H-P, Zhou L-S, Xia Y-K, Chen L-L, Yang C, Xiong Y*, Ye D*, Guan K-L.* Insulin and mTOR Pathway Regulate HDAC3-Mediated Deacetylation and Activation of PGK1. PLoS Biology. 2015;13(9):e1002243. (Previewed by PLOS Biology)

11.Hui Yang#, Lisha Zhou#, Qian Shi, Yuzheng Zhao, Huaipeng Lin, Mengli Zhang, Yi Yang, Zhi-Qiang Ling, Kun-Liang Guan*, Yue Xiong*, and Dan Ye*. SIRT3-dependent GOT2 acetylation enhances the malate-aspartate NADH shuttle activity to promote pancreatic tumor growth. EMBO J. 2015;34(8):1110-25.

12.Wang Y-P, Xiao M-T, Chen X-F, Chen L-L, Xu Y-P, Lv L, Wang P, Yang H, Ma S-H, Lin H-P, Jiao B, Ren R-B, Ye D*, Guan, K-L*, and Xiong Y*. WT1 recruits TET2 to regulate its target gene expression and suppress leukemia cell proliferation. Mol Cell. 2015; 57(4):662-73. (Previewed by Mol Cell)

13.Wang YP, Zhou LS, Zhao YZ, Wang SW, Chen LL, Liu LX, Ling ZQ, Hu FJ, Sun YP, Zhang JY, Yang C, Yang Y, Xiong Y, Guan KL, Ye D*. Regulation of G6PD acetylation by KAT9/SIRT2 modulates NADPH homeostasis and cell survival during oxidative stress. EMBO J. 2014; 33(12):1304-20.(Previewed by EMBO J)

14.Yang H. Lin H-P, Xu H-Y, Zhang L, Cheng L, Wen B, Shou J-Y, Guan K-L, Xiong Y, Ye D*. TET-catalyzed 5-methylcytosine hydroxylation is dynamically regulated by metabolites. Cell Research. 2014;24(8):1017-20.

15.Yang H, Liu Y, Bai F, Zhang J-Y, Ma S-H, Liu J, Xu Z-D, Zhu H-G, Ling Z-Q, Ye D*, Guan K-L* and Xiong Y*. Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation. Oncogene. 2013; 32(5):663-9. (入选ESI高被引论文)

16.Ye D, Ma S-H, XiongY , GuanK-L*. R-2-Hydroxyglutarate as the Key Effector of IDH Mutations Promoting Oncogenesis. Cancer Cell. 2013; 23(3):274-276.

17.Ye D*, Guan K-L* and Xiong Y*. The mechanisms of IDH mutations in tumorigenesis. Cell Research. 2012; 22 (7):1102-4. (Invited review)

18.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*, Guan KL.Inhibition of α-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes & Development. 2012; 26(12):1326-1338.(入选ESI高被引论文)


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