袁健，国家杰青及优青, 长期从事DNA损伤修复与肿瘤发生，肿瘤放化疗耐受分子机制研究，原创性阐明多个新的DNA损伤调控因子在肿瘤（卵巢癌、乳腺癌等）发生及放化疗耐药中的关键作用。相关工作发表在Cell，Nature Cell Biology、Molecular Cell，Nature Cancer，Science Advances，Nature Communications, Genes & Development， EMBO J等杂志。入选教育部新世纪人才计划，上海市浦江人才计划，担任科技部 973 项目环境应激致血管内皮细胞衰老、损伤及修复的分子机制课题组长。作为项目负责人主持国家自然科学基金重大项目1项，国家重大研究计划1项，国家自然科学基金面上项目2项，青年项目1项，省部级课题2项。
Yuan Jian, recipient of the National Outstanding Youth Science Foundation and National Excellent Youth Science Foundation. Professor Yuan has been engaged in DNA damage repair and tumorigenesis, research on molecular mechanism of tumor chemoradiotherapy resistance, and original elucidation of the key role of several new DNA damage regulators in tumor (ovarian cancer, breast cancer, etc.) genesis and chemoradiotherapy resistance. The related work has been published in journals such as Cell, Nature Cell Biology, Molecular Cell, Nature Cancer, Science Advances, Nature Communications, Genes& Development, EMBO J. Selected for the New Century Talent Program of the Ministry of Education and the Pujiang Talent Program of Shanghai, serving as the leader of the Molecular Mechanisms of Aging, Damage, and Repair of Vascular Endothelial Cells Caused by Environmental Stress in the 973 Project of the Ministry of Science and Technology. As the project leader, have charged one major project funded by the National Natural Science Foundation of China, one major research plan, two general projects funded by the National Natural Science Foundation of China, one youth project, and two provincial-level research projects.
代表性研究论文如下：
1.Chen Y#, Wu J#, Zhai L, Zhang T, Yin H, Gao H, Zhao F, Wang Z, Yang X, Jin M, Huang B, Ding X, Li R, Yang J, He Y, Wang Q, Wang W, Kloeber JA, Li Y, Hao B, Zhang Y, Wang J, Tan M, Li K, Wang P, Lou Z , Yuan J*. Metabolic regulation of homologous recombination repair by MRE11 lactylation. Cell. 2024 Jan 18;187(2):294-311.e21.
2.Li Y#, Li L#, Wang X#, Zhao F, Yang Y, Zhou Y, Zhang J, Wang L, Jiang Z, Zhang Y, Chen Y, Wu C, Li K, Zhang T, Wang P, Mao Z, Zhu W, Xu X, Liang S, Lou Z, Yuan J*. USP25 elevates SHLD2-mediated DNA double-strand break repair and regulates chemoresponse in cancer. Adv Sci (Weinh). 2024 Jul;11(28):e2403485.
3.Wu J#, Chen Y#, Li R#, Guan Y, Chen M , Yin H, Yang X, Jin M, Huang B, Ding X, Yang J, Wang Z, He Y, Wang Q, Luo J, Wang P, Mao Z, Michael S Y Huen, Lou Z, Yuan J*, Gong F*. Synergistic anticancer effect by targeting CDK2 and EGFR-ERK signaling. J Cell Biol. 2024 Jan 1;223(1):e202203005.
4.Huang J#, Wu C#, Kloeber JA, Gao H, Gao M, Zhu Q, Chang Y, Zhao F, Guo G, Luo K, Dai H, Liu S, Huang Q, Kim W, Zhou Q, Zhu S, Wu Z, Tu X, Yin P, Deng M, Wang L, Yuan J*, Lou Z*. SLFN5-mediated chromatin dynamics sculpt higher-order DNA repair topology. Mol Cell. 2023 Feb 25:S1097-2765(23)00083-7.
5.Zeng X#, Zhao F#, Cui G, Zhang Y, Deshpande RA, Chen Y, Deng M, Kloeber JA, Shi Y, Zhou Q, Zhang C, Hou J, Kim W, Tu X, Yan Y, Xu Z, Chen L, Gao H, Guo G, Liu J, Zhu Q, Cao Y, Huang J, Wu Z, Zhu S, Yin P, Luo K, Mer G, Paull TT, Yuan J*, Tao K*, Lou Z*. METTL16 antagonizes MRE11-mediated DNA end resection and confers synthetic lethality to PARP inhibition in pancreatic ductal adenocarcinoma. Nat Cancer. 2022 Sep;3(9):1088-1104.
6.Zhao F#, Kim W#, Gao H, Liu C, Zhang Y, Chen Y, Deng M, Zhou Q, Huang J, Hu Q, Chen SH, Nowsheen S, Kloeber JA, Qin B, Yin P, Tu X, Guo G, Qin S, Zhang C, Gao M, Luo K, Liu Y, Lou Z*, Yuan J*. ASTE1 promotes shieldin-complex-mediated DNA repair by attenuating end resection. Nat Cell Biol. 2021 Aug;23(8):894-904. doi: 10.1038
7.Wu C, Chang Y, Chen J, Su Y, Li L, Chen Y, Li Y, Wu J, Huang J, Zhao F, Wang W, Yin H, Wang S, Jin M, Lou Z, Zhu WG, Luo K, Zhang J*, Yuan J*.USP37 regulates DNA damage response through stabilizing and deubiquitinating BLM. Nucleic Acids Res. 2021 Nov 8;49(19):11224-11240.
8.Zhou Q#, Huang J#, Zhang C#, Zhao F, Kim W, Tu X, Zhang Y, Nowsheen S, Zhu Q, Deng M, Chen Y, Qin B, Luo K, Liu B, Lou Z, Mutter RW*, Yuan J* The bromodomain containing protein BRD-9 orchestrates RAD51-RAD54 complex formation and regulates homologous recombination-mediated repair. Nat Commun. 2020 May 26;11(1):2639.
9.Chen Y#, Wu J#, Liang G, Geng G, Zhao F, Yin P, Nowsheen S, Wu C, Li Y, Li L, Kim W, Zhou Q, Huang J, Liu J, Zhang C, Guo G, Deng M, Tu X, Gao X, Liu Z, Chen Y, Lou Z, Luo K, Yuan J*. CHK2-FOXK axis promotes transcriptional control of autophagy programs. Science Advances. 2020 Jan 1;6(1):eaax5819.
10.Kim W#, Zhao F#, Wu R, Qin S, Nowsheen S, Huang J, Zhou Q, Chen Y, Deng M, Guo G, Luo K, Lou Z*, Yuan J*. ZFP161 regulates replication fork stability and maintenance of genomic stability by recruiting the ATR/ATRIP complex. Nat Commun. 2019 Nov 22;10(1):5304. doi: 10.1038/s41467-019-13321-z.
11.Wu J#, Chen Y#, Geng G, Li L, Yin P, Nowsheen S, Li Y, Wu C, Liu J, Zhao F, Kim W, Zhou Q, Huang J, Guo G, Zhang C, Tu X, Gao X, Lou Z, Luo K*, Qiao H*, Yuan J*. USP39 regulates DNA damage response and chemo-radiation resistance by deubiquitinating and stabilizing CHK2. Cancer Letter. 2019 May 1;449:114-124.
12.Chenming Wu, Kuntian Luo, Fei Zhao, Ping Yin, Ying Song, Min Deng, Jinzhou Huang, Yuping Chen, Lei Li, SeungBaek Lee, JungJin Kim, Qin Zhou, Xinyi Tu, Somaira Nowsheen, Qifeng Luo, Xiumei Gao, Zhenkun Lou*, Zhongmin Liu*, Jian Yuan*. USP20 positively regulates tumorigenesis and chemoresistance through β-catenin stabilization. Cell Death&Differentiation. 2018 Nov;25(10):1855-1869.
13.Li L#, Liu T#, Li Y, Wu C, Luo K, Yin Y, Chen Y, Nowsheen S, Wu J, Lou Z*, Yuan J*. The deubiquitinase USP9X promotes tumor cell survival and confers chemoresistance through YAP1 stabilization. Oncogene. 2018 May;37(18):2422-2431.
14.Li Y, Luo K, Yin Y, Wu C, Deng M, Li L, Chen Y, Nowsheen S, Lou Z, Yuan J*. USP13 regulates the RAP80-BRCA1 complex dependent DNA damage response. Nat Commun. 2017 Jun 1;8: 15752.
15.Luo K, Li Y, Yin Y, Li L, Wu C, Chen Y, Nowsheen S, Hu Q, Zhang L, Lou Z, Yuan J*. USP49 negatively regulates tumorigenesis and chemoresistance through FKBP51-AKT signaling. EMBO J. 2017 May 15; 36 (10):1434-1446
16.Liu T#, Yu J#, Deng M, Yin Y, Zhang H, Luo K, Qin B, Li Y, Wu C, Ren T, Han Y, Yin P, Kim J, Lee S, Lin J, Zhang L, Zhang J, Nowsheen S, Wang L, Boughey J, Goetz MP, Yuan J*, Lou Z*. CDK46-dependent activation of DUB3 regulates cancer metastasis through SNAIL1. Nat Commun .2017 Jan 09; 8:13923
17.Luo K#, Li L#, Li Y, Wu C, Yin Y, Chen Y, Deng M, Nowsheen S, Yuan J*, Lou Z*. A phosphorylation-deubiquitination cascade regulates the BRCA2-RAD51 axis in homologous recombination. Genes Dev. 2016 Dec 01; 30 (23):2581-2595
18.Deng M, Yang X, Qin B, Liu T, Zhang H, Guo W, Lee SB, Kim JJ, Yuan J, Pei H, Wang L, Lou Z. Deubiquitination and Activation of AMPK by USP10. Mol Cell. 2016 Feb 18; 61 (4):614-24
19.Luo K, Deng M, Li Y, Wu C, Xu Z, Yuan J*, Lou Z*. CDK-mediated RNF4 phosphorylation regulates homologous recombination in S-phase. Nucleic Acids Res .2015 Jun 23; 43 (11):5465-75
20.Oi N#, Yuan J#, Malakhova M, Luo K, Li Y, Ryu J, Zhang L, Bode AM, Xu Z, Lou Z, Dong Z. Resveratrol induces apoptosis by directly targeting Ras-GTPase-activating protein SH3 domain-binding protein 1. Oncogene 2015 May 14; 34 (20):2660-71
21.Liu T, Lin YH, Leng W, Jung SY, Zhang H, Deng M, Evans D, Li Y, Luo K, Qin B, Qin J, Yuan J*, Lou Z*. A divergent role of the SIRT1-TopBP1 axis in regulating metabolic checkpoint and DNA damage checkpoint. Mol Cell. 2014 Dec 4; 56 (5):681-95
22.Yuan J*, Luo K, Deng M, Li Y, Yin P, Gao B, Fang Y, Wu P, Liu T, Lou Z*. HERC2-USP20 axis regulates DNA damage checkpoint through Claspin. Nucleic Acids Res. 2014 Dec 01; 42 (21):13110-21
23.Qin B, Gao B, Yu J, Yuan J*, Lou Z*. Ataxia telangiectasia-mutated- and Rad3-related protein regulates the DNA damage-induced G2/M checkpoint through the Aurora A cofactor Bora protein. J Biol Chem. 2013 May 31; 288 (22):16139-44
24.Luo K, Zhang H, Wang L, Yuan J*, Lou Z*. Sumoylation of MDC1 is important for proper DNA damage response. EMBO J. 2012 Jun 29; 31(13):3008-19.
25.Yuan J*, Luo K, Liu T, Lou Z*. Regulation of SIRT1 activity by genotoxic stress. Genes Dev. 2012 Apr 15; 26 (8):791-6.
