姓 名: | 林忠辉 | |
性 别: | 男 |
|
职 称: | 研究员(国家高层次青年人才、闽江学者特聘教授) | |
学 历: | 博士 | |
专 业: | 化学生物学/结构生物学/药理学 | |
电子邮件: | zhonghui.lin@fzu.edu.cn | |
研究方向: | 药物靶标的结构与功能研究及药物发现 |
***招生/招聘***:欢迎报考药学、分析化学、生物化工等专业硕/博士研究生。本课题组常年招聘结构生物学、化学生物学和药理学方向福建省引进生和博士后。有意者请将求职意向和个人简历发送到zhonghui.lin@fzu.edu.cn。博士后待遇:https://mp.weixin.qq.com/s/Cs31d3ouYbV7Zx8fG9130A;福建省引进生待遇:https://mp.weixin.qq.com/s/ioBU8pFXvK4ghUHYJ-DTTw。
教育和工作经历
2017.04-至今 福州大学,365365最快线路检测中心,研究员
2011.11-2017.03 美国西南医学中心(UT Southwestern Medical Center,TX USA),博士后
2009.07-2011.10 中科院福建物质结构研究所,博士后
2006.09-2009.07 中科院上海药物研究所,药物设计学/博士
2003.09-2006.07 福建农林大学,生物化学与分子生物学/硕士
1999.09-2003.07 福建农林大学,生物科学/学士
教学简介
本科 《分析化学》
研究生 《化学生物学前沿》
科研简介
本课题组致力于探索细胞应对DNA损伤及外源核酸入侵的分子调控机制,同时还开展以这些过程的关键调控蛋白为靶标的抗肿瘤、抗病毒、抗菌等药物的研发。相关研究成果以第一作者或通讯作者发表在Nature,Nat Chem Biol,Nat Commun,EMBO J,Nucleic Acids Res等国际主流刊物上。
科研项目
国家自然科学基金面上项目(32471255),2025.01-2028.12,项目负责人
福建省自然科学基金重点项目(2024J02006),2024.11-2027.11,项目负责人
国家自然科学基金面上项目(31971222),2020.01-2023.12,项目负责人
福建省百人计划项目(2018年),项目负责人
福建高校领军人才项目(2018年),项目负责人
国家高层次青年人才启动项目(2017年),项目负责人
课题组成员
博士生:朱钦未、李若愚、陈雪宁、陈靖轩、林染荀
硕士生:陈晓艺、陈长锟、陈绪龙、石如奕、詹彬彬、叶宇豪、傅贤洪
已毕业学生:
博士:林华建、张旭、杜丽阳、张丹萍
硕士:胡逸、何裕华、华正康、戴琳、卢莲、方倩倩、陈浩、李鑫、宋卓蓉、郭彬彬、蔡凯丽、李隆亨
代表性论文
2024年
*. Discovery of KPT-6566 as STAG1/2 Inhibitor sensitizing PARP and NHEJ Inhibitors to suppress tumor cells growth in vitro. DNA Repair. 2024, 144, 103784. doi: 10.1016/j.dnarep.2024.103784
Xuening Chen,Zhonghui LinQinwei Zhu#, Liyang Du#, Juhong Wu#, Jinyu Li*, Zhonghui Lin*. Walrycin B, as a novel separase inhibitor, exerts potent anticancer efficacy in a mouse xenograft model. Biochemical Pharmacology. 2024. Aug 20,116502. doi: 10.1016/j.bcp.2024.116502
Danping Zhang, Liyang Du, Haishan Gao, Cai Yuan*,Zhonghui Lin*. Structural insight into the Csx1-Crn2 fusion self-limiting ribonuclease of type III CRISPR system. Nucleic Acids Research. 2024, 1–12. doi: 10.1093/nar/gkae569
Danping Zhang, Shenjie Xu, Zhipu Luo*, Zhonghui Lin*. MOC1 cleaves Holliday Junctions through a cooperative nick and counter-nick mechanism mediated by metal ions. Nat Commun. 2024,15: 5140-5149.doi:10.1038/s41467-024-49490-9
Xuening Chen, Changkun Chen, Chengmiao Luo, Jianyong Liu, Zhonghui Lin*.Discovery of UMI-77 as a novel Ku70/80 inhibitor sensitizing cancer cells to DNA damaging agents in vitro and in vivo. European Journal of Pharmacology. 2024,975: 176647.doi:10.1016/j.ejphar.2024.176647.
Longheng Li, Binbin Guo, Lin Dai, Chun Liu*, Zhonghui Lin*. Ebselen and TPI-1, as RecG helicase inhibitors, potently enhance the susceptibility of Pseudomonas aeruginosa to DNA damage agents.Biochemical Pharmacology.2024,222: 116051. DOI:10.1016/j.bcp.2024.116051
Liyang Du, Qinwei Zhu and Zhonghui Lin*. Molecular mechanism of allosteric activation of the CRISPR ribonuclease Csm6 by cyclic tetra-adenylate. EMBO J. 2024,43:304. DOI:10.1038/s44318-023-00017-w
2023年
Xu Zhang, Xuening Chen, Lian Lu, Qianqian Fang, Chun Liu, Zhonghui Lin*.Identification of small-molecule inhibitors of human MUS81-EME1/2 by FRET-based high-throughput screening.Bioorg Med Chem.2023,90:117383.doi: 10.1016/j.bmc.2023.117383.
Xu Zhang#, Zixuan Zhou#, Lin Dai, Yulin Chao, Zheng Liu, Mingdong Huang, Qianhui Qu*, Zhonghui Lin*.Cryo-EM structure of the RuvAB-Holliday junction intermediate complex from Pseudomonas aeruginosa.Front. Plant Sci.2023,14:1139106. doi: 10.3389/fpls.2023.1139106.
Liyang Du, Danping Zhang, Zhipu Luo*, Zhonghui Lin*.Molecular basis of stepwise cyclic tetra-adenylate cleavage by the type III CRISPR ring nuclease Crn1/Sso2081. Nucleic Acids Research.2023,51(5):2485-2495.doi:10.1093/nar/gkad101.
方倩倩#,陈浩#,廖馨源,林忠辉*.限制性核酸内切酶Asc I 蛋白质的表达纯化、酶活测定及小角散射结构解析[J/OL].中国生物化学与分子生物学报.2023-02-07.https://doi.org/10.13865/j.cnki.cjbmb.2022.12.1482.(该论文获“郑集-张昌颖优秀论文奖励基金”,中国生物化学与分子生物学会度优秀论文,2023年)
2022年
Lin Dai, Lian Lu, Xu Zhang,Juhong Wu, Jinyu Li, Zhonghui Lin*.Identification of small-molecule inhibitors of the DNA repair proteins RuvAB from Pseudomonas aeruginosa.Bioorg Med Chem. 2022,73:117022. doi: 10.1016/j.bmc.2022.117022.
Yuhua He, Wei Fu, Liyang Du, Huiqiao Yao, Zhengkang Hua, Jinyu Li, Zhonghui Lin*. Discovery of a novel Aurora B inhibitor GSK650394 with potent anticancer and anti-aspergillus fumigatus dual efficacies in vitro.J Enzyme Inhib Med Chem. 2022,37:109-117. doi: 10.1080/14756366.2021.1975693.
DeChao Yang, LinFeng Wen, Liyang Du, ChengMiao Luo, ZiYao Lu, JianYong Liu*, Zhonghui Lin*. A Hypoxia-Activated Prodrug Conjugated with a BODIPY-Based Photothermal Agent for Imaging-Guided Chemo-Photothermal Combination Therapy.ACS Appl Mater Interfaces.2022,14:40546-40558. doi: 10.1021/acsami.2c09071.
Lian Lu, Yun Peng, Huiqiao Yao, Yanqun Wang, Jinyu Li*, Yang Yang*, Zhonghui Lin*. Punicalagin as an allosteric NSP13 helicase inhibitor potently suppresses SARS-CoV-2 replication in vitro.Antiviral Res. 2022,206:105389. doi: 10.1016/j.antiviral.2022.105389.
DeChao Yang, XiaoZhen Yang, ChengMiao Luo, LinFeng Wen, JianYong Liu*, Zhonghui Lin*. A promising strategy for synergistic cancer therapy by integrating a photosensitizer into a hypoxia-activated prodrug.Eur J Med Chem. 2022,243:114749. doi: 10.1016/j.ejmech.2022.114749.
Qianqian Fang, Zhengkang Hua, Zhonghui Lin*. A protocol to determine the activities of human MUS81-EME1&2 endonucleases.STAR Protoc. 2022 ,3:101528. doi: 10.1016/j.xpro.2022.101528.
Zhengkang Hua, Qianqian Fang, Danping Zhang, Zhipu Luo, Cai Yuan,Zhonghui Lin*. Crystal structure of the human MUS81-EME2 complex.Structure. 2022,30:743-752.e3. doi: 10.1016/j.str.2022.02.015.
2021年
DeChao Yang, Shuai Wang, XiaoLu Weng, HongXia Zhang, JianYong Liu, Zhonghui Lin*. Singlet Oxygen-Responsive Polymeric Nanomedicine for Light-Controlled Drug Release and Image-Guided Photodynamic-Chemo Combination Therapy.ACS Appl Mater Interfaces. 2021,13:33905-33914. doi: 10.1021/acsami.1c09044.
2020年
Yi Hu, Yuhua He, Zonghui Lin*.Biochemical and structural characterization of the Holliday junction resolvase RuvC from Pseudomonas aeruginosa.Biochem Biophys Res Commun. 2020,525:265-271. doi: 10.1016/j.bbrc.2020.02.062.
2019年
Huajian Lin#, Danping Zhang#, Ke Zuo#, Cai Yuan, Jinyu Li*, Mingdong Huang*, Zhonghui Lin*.Structural basis of sequence-specific Holliday junction cleavage by MOC1.Nat Chem Biol. 2019,15:1241-1248. doi: 10.1038/s41589-019-0377-4.
2018年
Lee HS, Lin Z, Chae S, Yoo YS, Kim BG, Lee Y, Johnson JL, Kim YS, Cantley LC, Lee CW, Yu H, Cho H.The chromatin remodeler RSF1 controls centromeric histone modifications to coordinate chromosome segregation.Nat Commun. 2018,9:3848. doi: 10.1038/s41467-018-06377-w.
2017年以前
Zhonghui Lin, Xuelian Luo, Hongtao Yu*. Structural basis of cohesin cleavage by separase. Nature. 2016, 532: 131-134.
Zhonghui Lin#, Luying Jia#, Diana R. Tomchick, Xuelian Luo, Hongtao Yu*. Substrate-specific activation of the mitotic kinase Bub1 through intramolecular autophosphorylation and kinetochore targeting. Structure. 2014, 22:1-12.
Zhonghui Lin#, Jan K. Jensen#, Zebin Hong, Xiaoli Shi, Lihong Hu, Peter A. Andreasen, and Mingdong Huang*. Structural insight into inactivation of plasminogen activator inhibitor-1 by a small-molecule antagonist. Chemistry & Biology. 2013, 20:253-61.
Zhonghui Lin, Longguang Jiang, Cai Yuan, Jan K.Jensen, Xu Zhang, Zhipu Luo, Barbara C. Furie, Bruce Furie, Peter A. Andreasen, Mingdong Huang*. Structural basis for recognition of urokinase-type plasminogen activator by plasminogen activator inhibitor-1. J. Biol. Chem. 2011, 286: 7027-32.
Zhonghui Lin, Yu Zhang, Yinan Zhang, Hong Shen, Lihong Hu, Hualiang Jiang, and Xu Shen*. Oleanolic acid derivative NPLC441 potently stimulates glucose transport in 3T3-L1 adipocytes via multi-target mechanism. Biochemical Pharmacology. 2008, 76:1251-62.
获奖情况
福州大学杰出青年教师励志奖(2021)
福州大学青年五四奖章(2019年)
福建省“向上向善育人工程基金”奖教金 (2019年)
美国西南医学中心药理系年度优秀博士后(2016年)
国际血栓与止血协会“第三世界科学家奖”(2011年)