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郭志刚

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郭志刚

科技部青年973首席科学家

南京师范大学生命科学学院教授、博士生导师

通讯地址:江苏省南京市文苑路1号,邮编:210023

E-mail: guo@njnu.edu.cn

基本情况

江苏省生物化与分子生物学学会副理事长、江苏省发育与细胞生物学会副理事长、江苏省分子医学生物技术重点实验室主任。


作为首席科学家承担科技部青年973项目—DNA损伤修复与肿瘤研究。在《Molecular Cell》、《Nature Chemical Biology》、《Journal of Hematology & Oncology》、《EMBO R》、《Oncogene》等一流期刊上发表高水平SCI论文近百篇。深入地揭示了DNA损伤与肿瘤发生、发展和耐药的分子机制。特别地,发现了DNA修复抑制剂可以调控肿瘤微环境,促进抗体药物和CAR-T对实体肿瘤的浸润,从而打破实体瘤治疗瓶颈。特别地,为CAR-T治疗实体瘤提供了新的方案。由此提出了“基于DNA修复抑制的抗肿瘤策略”。获国家侨界贡献奖、江苏青年科技奖、江苏省高校科技成果一等奖。带领团队产学研转化,获得三个国家一类新药临床批件(适应症为晚期实体肿瘤、血液瘤和卵巢癌)。获中国产学研创新促进奖。其中靶向间皮素的自体CAR-T细胞注射液为国内首创,用于治疗晚期复发卵巢癌,临床数据表明其安全性和有效性居世界前列。


指导研究生获校优秀博士论文奖、全国大学生互联网+竞赛江苏一等奖以及国赛铜奖。


人才称号

教育部新世纪优秀人才(2014)

江苏省双创人才(2011)

江苏省杰出青年基金获得者(2013)

南京师范大学百名青年领军人才(2014)

江苏省六大人才高峰计划(2015)

江苏省333工程第三层次(2014)


荣誉、奖励和主要基金项目

江苏省高校科技研究成果一等奖(2021)

中国产学研创新促进奖(2021)

辽宁省科技进步二等奖(2019)

青年973计划首席科学家(2013)

国家科技部、卫计委重大项目二审评审专家(2016,2017,2018,2019)

第5届国家侨界贡献奖(创新人才)(2014.9)

教育部新世纪优秀人才计划(2014)

江苏省双创人才(2011)

江苏杰出青年基金(2013)

第14届江苏省青年科技奖(2014)

江苏省六大人才高峰计划(2015)

江苏省333工程第三层次人才

江苏省科协青年会员创新创业大赛二等奖(2016)

南京市第10届自然科学论文奖一等奖(2014)

南京师范大学优秀教师(2012,2022)



学术兼职

美国科学促进会、美国肿瘤研究会、美国Sigma科学研究会会员、中国生物化学与分子生物学会理事、中国细胞生物学会医学细胞生物学分会理事、江苏省发育与细胞生物学会副理事长、江苏省生物化学与分子生物学学会副理事长、中国生物化学与分子生物学会理事。



主要研究方向

细胞DNA修复能力是维持生命健康的关键因素之一,同时与肿瘤的发生、发展耐药关系密切。一方面,在正常细胞内,DNA修复是细胞对抗DNA损伤,维持细胞正常功能的核心机制。DNA修复能力缺陷通常导致多种疾病的发生。另一方面,在肿瘤细胞内,DNA修复能力被过度激活,使得肿瘤细胞耐受放化疗治疗。此外,DNA修复还参与机体免疫系统功能调控,影响肿瘤微环境,从而改变肿瘤对免疫治疗药物的响应。因此,研究DNA修复的分子机制,开发靶向DNA修复的抗肿瘤药物,具有重要的理论意义与临床转化价值。


1) DNA损伤修复的分子机制研究与靶向DNA修复酶的小分子药物开发

本方向研究包括两个方面的内容:i) DNA修复酶结构功能、基因组稳定性与肿瘤发生、发展、耐药的关系;ii)靶向DNA修复酶的抗肿瘤药物开发。

在前期的研究工作中,本课题组揭示了DNA碱基切除修复途径中关键酶(FEN1, APE1, OGG1, Pol β)在DNA修复中的重要作用及其调控机制;同时,筛选了多个DNA修复抑制剂,用于抗肿瘤研究。


2) 靶向DNA修复促进抗体药物抗肿瘤机制研究及药物开发

抗体是迄今为止抗肿瘤药物的最主要分子形式,全球排名前10的抗肿瘤药大多为抗体分子。然而,由于肿瘤微环境的存在,抗体药物对实体肿瘤的浸润受到阻碍,严重影响肿瘤治疗效果。本课题组发现DNA修复抑制剂可以激活cGAS-Sting通路,促进细胞因子的分泌,从而有利于抗体药物穿透实体瘤屏障。本实验室拥有世界先进的全人源噬菌体抗体库平台,开发了包括pcsk9抗体在内的多个抗肿瘤药物。在开发新一代抗体药物的基础上,聚焦DNA修复抑制剂促进抗体药物抗肿瘤机制和转化应用研究。


3) 靶向DNA修复促进CAR-T实体瘤治疗的机制研究及药物开发

CAR-T是目前治疗肿瘤最有效的手段之一,特别在血液瘤领域,取得重大突破。然而,在实体瘤领域,由于肿瘤微环境的限制,CAR-T治疗效果一直不理想。本课题组发现,DNA修复抑制剂可以激活机体自身免疫系统,促进T细胞对实体肿瘤的浸润,从而打破CAR-T对实体瘤治疗的瓶颈。目前,本课题组与企业和医院联合,开发了多个实体瘤CAR-T,正在进行临床研究,效果良好。聚焦DNA修复抑制剂促进细胞免疫治疗的机制研究,开发新的细胞免疫治疗手段。研究重点在于开发安全、有效、低成本(通用型)细胞治疗药物。

承担的主要课题

国家科技部青年973计划、国家自然科学面上项目、教育部新世纪优秀人才支持计划、教育部博士点基金、江苏省杰出青年基金、江苏科技厅重大研究项目,江苏省双创计划、其它部省级、横向课题多项。

主要专利及成果转化

1. 一种RVG-CD70 CAR-T细胞及其制备方法与应用

专利号:ZL 202010054260.2

2. PARP抑制剂联合CAR-T细胞在制备抗肿瘤药物中的应用

申请(专利)号:CN202110011813.0

3. 针对PCSK9的全人源抗体可变区基因及其应用;

专利号:ZL 201510205553.5

4. 一种-CD70 CAR-T细胞制剂及其制备方法与应用。

专利号:ZL201910857176.1

5. Small molecule compound and derivative thereof

澳大利亚革新专利,专利号:2020101410

6. Doxorubicin combined medicine and its application

澳大利亚革新专利,专利号:2020101830

7. 抗人GPC3单克隆抗体;专利号:ZL201911053957.1

8. 抗人MSLN单克隆抗体及其应用

专利号:ZL202010447170.X

9. 一种基于光亲和共价连接的蛋白质分子弱相互作用捕获磁珠及其制备

方法和应用

专利号:ZL 2019 1 1247058.5

代表性论文

1. Feng Ji*,Luxia Xu, Kaili Long, Fan Zhang, Miaomiao Zhang, Xiao Lu, Mingyue Xia, Jiannan Chen, Yu Du, Yong Tang, Heming Wu, Yan Shi, Ruiting Ma, Jun Li, Zhengliang Chen, Bin Xu, Qi Zhang, Junqing Liang, Shaochang Jia, Zhigang Hu*, Zhigang Guo*. Rabies virus glycoprotein 29 (RVG29) promotes CAR-T immunotherapy for glioma. Translational Research 2023 Mar 26;S1931-5244(23)00054-3.(影响因子10.17)

全文链接:https://www.translationalres.com/article/S1931-5244(23)00054-3/fulltext

成果报道:http://www.njnu.edu.cn/info/1088/19006.htm

2. Jiannan Chen; Jianhua Hu; Lili Gu; Feng Ji; Fan Zhang; Miaomiao Zhang; Jun Li; Zhengliang Chen; Longwei Jiang; Yan Zhang; Ruifang Shi; Lihua Ma; Shaochang Jia; Ying Zhang; Qi Zhang; Junqing Liang; Shunyu Yao; Zhigang Hu*; Zhigang Guo(郭志刚)*.Anti-mesothelin CAR-T immunotherapy in patients with ovarian cancer.Cancer Immunology, Immunotherapy, 2023, 72(2): 409 (影响因子6.6)

全文链接:https://link.springer.com/article/10.1007/s00262-022-03238-w

成果报道:http://www.njnu.edu.cn/info/1038/17760.htm

3. Tongmin Xue; Shanmeizi Zhao; Hong Zhang; Ting Tang; Lu Zheng; Jun Jing; Xie Ge; Rujun Ma; Jinzhao Ma; Xiaoyan Ren; KadiliyaJueraitetibaike; Zhigang Guo(郭志刚)*; Li Chen*; Bing Yao*. PPT1 Regulation Of HSP90α Depalmitoylation Participates In The Pathogenesis Of Hyperandrogenism. iScience, 2023, 26: 106131

全文链接:https://www.cell.com/action/showPdf?pii=S2589-0042%2823%2900208-0

4. Munan Shi; Jiajia Hou; Shan Shao; Weichu Liang; Shiwei Wang; Yuzhou Yang; Zhigang Guo(郭志刚)*; Feiyan Pan*. Short-Term Starvation Weakens the Efficacy of Cell Cycle Specific Chemotherapy Drugs through G1 Arrest. International Journal of Molecular Sciences, 2023, 24(3): 2498 (影响因子6.2)

全文链接:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917170/pdf/ijms-24-02498.pdf

5. Ying Ma; Yang Yang; Jingyu Xin; Lingfeng He; Zhigang Hu; Tao Gao; Feiyan Pan; ZhigangGuo.RNA G-Quadruplex within the 5′-UTR of FEN1 Regulates mRNA Stability under Oxidative StressAntioxidants, 2023, 12(2): 276 (影响因子7.67)

全文链接:https://www.mdpi.com/2076-3921/12/2/276

成果报道:http://sky.njnu.edu.cn/info/1033/6153.htm

6. Enjie Li , Mingyue Xia , Yu Du , Kaili Long, Feng Ji, Feiyan Pan, LingfengHe,Zhigang Hu*, Zhigang Guo(郭志刚)* METTL3 promotes homologous recombination repair and modulates chemotherapeutic response in breast cancer by regulating the EGF/RAD51 axis eLife 2022;11:e75231.(影响因子8.7)

全文链接:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9094751/pdf/elife-75231.pdf

成果报道:http://www.njnu.edu.cn/info/1038/17352.htm

7. Mingyue Xia; Shuyan Wang; Yannan Qi; Kaili Long; Enjie Li; Lingfeng He; Feiyan Pan; Zhigang Guo*(郭志刚); Zhigang Hu*. Inhibition of O-GlcNAc transferase sensitizes prostate cancer cells to docetaxel. Frontiers in Oncology, 2022, 12: 1

全文链接:https://www.frontiersin.org/articles/10.3389/fonc.2022.993243/full

8. Ji, Feng; Zhang, Fan; Zhang, Miaomiao; Long, Kaili; Xia, Mingyue; Lu, Fei; Li, Enjie; Chen, Jiannan; Li, Jun; Chen, Zhengliang; Jing, Li; Jia, Shaochang; Yang, Rong; Hu, Zhigang*; GUO Z(郭志刚)* Targeting the DNA damage response enhances CD 70-CAR-T cell therapy for renal carcinoma by activativatingcGAS-STING pathway. Journal of Hermatology& Oncology(2021)14:152(影响因子23.1)

全文链接:https://jhoonline.biomedcentral.com/articles/10.1186/s13045-021-01168-1

成果报道:http://www.njnu.edu.cn/info/1038/15990.htm

9. Long, Kaili; Gu, Lili; Li, Lulu; Zhang, Ziyu; Li, Enjie; Zhang, Yilan; He, Lingfeng; Pan, Feiyan;GUO Z(郭志刚)*; Hu, Zhigang*. Small-molecule inhibition of APE1 induces apoptosis, pyroptosis, and necroptosis in non-small cell lung cancer. Cell Death & Disease, 2021, 12(6): 503-517. (影响因子9.68)

全文链接:https://www.nature.com/articles/s41419-021-03804-7

成果报道:http://www.njnu.edu.cn/info/1038/15461.htm

10. Wentao Wang; Ying Ma; Miaoling Huang; Weichu Liang; Xingqi Zhao; Qianwen Li; Shiwei Wang; Zhigang Hu; Lingfeng He; Tao Gao; Jinfei Chen; Feiyan Pan; GUO Z(郭志刚)* Asymmetrical arginine dimethylation of histone H4 by 8-oxog/OGG1/PRMT1 is essential for oxidative stress-induced transcription activation. Free Radical Biology & Medicine. 2021 Feb;164:175-186(影响因子8.1)

全文链接:https://doi.org/10.1016/j.freeradbiomed.2020.12.457

成果报道:http://www.njnu.edu.cn/info/1038/14870.htm

11. YilanZhang, QiZhang, LuLuLi, DanMu, KeHua, ShushengCi, Lei Shen, LiZheng, Binghui Shen∗, GUO Z(郭志刚)∗. Arginine methylation of APE1 promotes its mitochondrial translocation to protect cells from oxidative damage.Free Radical Biology and Medicine, 2020;158:60-73.(影响因子8.1)

全文链接:https://doi.org/10.1016/j.freeradbiomed.2020.06.027

成果报道:http://sky.njnu.edu.cn/info/1033/3836.htm

12. Mingyue Xia, Zhigang Guo * and Zhigang Hu *The Role of PARP Inhibitors in the Treatment of Prostate Cancer: Recent Advances in Clinical Trials. Biomolecules 2021, 11, 722.(影响因子6.06)

全文链接:https://doi.org/10.3390/biom11050722

13. Zhuang Ma ,Wentao Wang, Shiwei Wang , Xingqi Zhao , Ying Ma , Congye Wu , Zhigang Hu, Lingfeng He , Feiyan Pan *, GUO Z(郭志刚)*. Symmetrical Dimethylation of H4R3: A Bridge Linking DNA Damage and Repair Upon Oxidative Stress.Redox Biology. 2020 Jul 24:101653. doi: 10.1016/j.redox.2020.101653. PMID: 32739156.(影响因子10.78)

全文链接:https://doi.org/10.1016/j.redox.2020.101653

成果报道:http://sky.njnu.edu.cn/info/1033/3837.htm

14. Meina Wang,Kaili Long,Enjie Li,Lulu Li,Binghua Li,Shusheng Ci,Lingfeng He,Feiyan Pan,Zhigang Hu*, GUO Z(郭志刚)*. DNA polymerase beta modulates cancer progression via enhancing CDH13 expression by promoter demethylation.Oncogene, 2020 Aug;39(33):5507-5519.(影响因子8.7)

全文链接:https://www.nature.com/articles/s41388-020-1386-1

成果报道:http://sky.njnu.edu.cn/info/1033/3833.htm

15. Xiao Lu, Rui Liu, LuLu Li, Zhigang Hu*,GUO Z(郭志刚)* .MicroRNA-140 impedes DNA repair by targeting FEN1 and enhances chemotherapeutic response in breast cancer.Oncogene(2020) 39:234–247(影响因子8.7)

全文链接:https://www.nature.com/articles/s41388-019-0986-0

成果报道:http://sky.njnu.edu.cn/info/1073/4923.htm

16. Hua K, Wang L, Sun J, Zhou N, Zhang Y, Ji F, Jing L, Yang Y, Xia W, Hu Z, Pan F, Chen X, Yao B,GUO Z(郭志刚)*. Impairment of Pol β-related DNA Base-excision Repair Leads to Ovarian Aging in Mice.Aging(Albany NY). 2020 Nov 20;12. doi: 10.18632/aging.104123. PMID: 33223510.(影响因子5.6)

全文链接:https://doi.org/10.18632/aging.104123

成果报道:http://sky.njnu.edu.cn/info/1033/3849.htm

17. Lingfeng He, Zhigang Hu, Yuling Sun, Miaomiao Zhang, Hongqiao Zhu , Longwei Jiang, Qi Zhang, Dan Mu, Jing Zhang, Lili Gu, Yang Yang, Fei-Yan Pan, Shaochang Jia ,GUO Z(郭志刚)*.PRMT1 is critical to FEN1 expression and drug resistance in lung cancer cells.DNA Repair(Amst). 2020 Nov;95:102953. doi: 10.1016/j.dnarep.2020.102953.(影响因子4.3)

全文链接:https://doi.org/10.1016/j.dnarep.2020.102953

成果报道:http://sky.njnu.edu.cn/info/1033/3841.htm

18. Shusheng Ci, Wen Xia, Weichu Liang, Lihong Qin,Yilan Zhang, Grigory L. Dianov, Meina Wang, Xingqi Zhao, Congye Wu, Karthick Kumar Alagamuthu, zhigang Hu ,Lingfeng He, Feiyan Pan, GUO Z(郭志刚). Src‐mediated phosphorylation of GAPDH regulates its nuclear localization and cellular response to DNA damage. FASEB J, 2020, 34(8):10443-10461(影响因子5.8)

全文链接:https://doi.org/10.1096/fj.201902904RR

成果报道:http://sky.njnu.edu.cn/info/1033/3826.htm

19. Rui Liu, Meina Wang, Enjie Li, Yang Yang, Jiaxin Li, Siyu Chen, Wen-Jun Shen,SalmanAzhar,GUO Z(郭志刚), Zhigang Hu*. Dysregulation of microRNA-125a contributes to obesity-associated insulin resistance and dysregulates lipid metabolism in mice .Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 2020, 1865(5):158640.(影响因子6.6)

全文链接:https://doi.org/10.1016/j.bbalip.2020.158640

20. Tao Gao, Songyan Zhao, Junhua Sun, Qiongbo Huang, Shipeng Long, MingmingLv, Jiehua Ma,Zhigang Guo, and GenxiLi.Single-Cell Quantitative Phenotyping via the Aptamer-Mounted Nest-PCR (Apt-nPCR).Analytical Chemistry 2022 94 (5), 2383-2390DOI: 10.1021/acs.analchem.1c03865(影响因子8.0)

全文链接:https://pubs.acs.org/doi/10.1021/acs.analchem.1c03865

21. Ting Wu, Hongqiao Zhu, Miaomiao Zhang , Yuling Sun , Yongjing Yang ,Lili Gu ,Jing Zhang, Dan Mu,Congye Wu , Zhigang Hu, Longwei Jiang , Shaochang Jia ,Ying Zhang, Lingfeng He, Fei-Yan Pan, Zhigang Guo. FEN1 inhibitor synergizes with low-dose camptothecin to induce increased cell killing via the mitochondria mediated apoptotic pathway.Gene Ther (2021).(影响因子4.1)

全文链接:https://doi.org/10.1038/s41434-020-00215-9

22. Jing Zhang,Li Jing, Subee Tan, Er-Ming Zeng, Yingbo Lin, Lingfeng He , Zhigang Hu , Jianping Liu andGUO Z(郭志刚)*.Inhibition of miR-1193 leads to synthetic lethality in glioblastoma multiforme cells deficient of DNA-PKcs.Cell Death & Disease, (2020) 11:602.(影响因子9.68)

全文链接:https://www.nature.com/articles/s41419-020-02812-3

成果报道:http://sky.njnu.edu.cn/info/1033/3838.htm

23. Mengyuan He, Jiarong Guo, Jiahua Yang, Yang Yang, Songyan Zhao, QiaoXu,TiangxiangWei,DavideMari,Ferraris,Tao Gao*,GUO Z(郭志刚)*. A highly selective electrochemical assay based on the Sakaguchi reaction for the detection of protein arginine methylation state.Electrochemistry Communications.(影响因子5.4)

全文链接:https://doi.org/10.1016/j.elecom.2020.106808.

24. YangYang, MengyuanHe,TianxiangWei ,JunhuaSun,ShaohuaWu,TaoGao*,GUO Z(郭志刚)*. Photo-affinity pulling down of low-affinity binding proteins mediated by post-translational modifications.Analytica Chimica Acta, 2020, 1107:164-171.(影响因子6.91)

全文链接:https://doi.org/10.1016/j.aca.2020.02.016

25. Lulu Li, Alagamuthu Karthick Kumara, Zhigang Hua,* andGUO Z(郭志刚)*.Small Molecule Inhibitors Targeting Key Proteins in the DNADamage Response for Cancer Therapy.Current Medicinal Chemistry, 2020, 27, 1-19.(影响因子4.7)

全文链接:https://www.eurekaselect.com/article/104754

26. Meina Wang, Enjie Li, Lin Lin, Alagamuthu Karthick Kumar, Feiyan Pan, LingfengHe,Jing Zhang, Zhigang Hu*, and GUO Z(郭志刚)*. Enhanced Activity of Variant DNA Polymerase β (D160G) Contributes to Cisplatin Therapy by Impeding the Efficiency of NER.Molecular Cancer Research,2019,17(10):2077-2088.(影响因子6.3)

全文链接:https://doi.org/10.1158/1541-7786.MCR-19-0482

成果报道:http://sky.njnu.edu.cn/info/1073/4923.htm

27. Jing Zhang, Su-Bee Tan,GUO Z(郭志刚)*.CD47 decline in pancreatic islet cells promotes macrophage-mediated phagocytosis in type I diabetes.World Journal of Diabetes.2020 Jun 15;11(6):239-251. (影响因子4.5)

全文链接:https://www.wjgnet.com/1948-9358/full/v11/i6/239.htm

28. Xue Zeng,XiujuanQu,ChenyangZhao,LuXu,KezuoHou,YunpengLiu,NaZhang,JingFeng,ShaShi,LingyunZhang,iawen Xiao,GUO Z(郭志刚),Yuee Teng, Xiaofang Che*.FEN1 mediates miR‐200a methylation and promotes breast cancer cell growth via MET and EGFR signaling.The FASEB J, 2019, 33(10).(影响因子5.8)

全文链接:https://doi.org/10.1096/fj.201900273R

29. JinLi Li,JianPing Wang,Hong Chang,ShengMing Deng,JiaHui Du,Xiao‐Xiao Wang,HeJuan Hu,DongYin Li,XiangBin Xu,WeiQiang Guo,Yao‐Hua Song,GUO Z(郭志刚),MinXuan Sun,YiWei Wu,SongBai Liu*.FEN1 inhibitor increases sensitivity of radiotherapy in cervical cancer cells.Cancer Medicine,2019 Dec;8(18):7774-7780.(影响因子4.7)

全文链接:https://doi.org/10.1002/cam4.2615

30. Wen Xia, Suseng Ci, Menghan Li, Xingqi Zhao, Feiyan Pan *,GUO Z(郭志刚)*.Two-way crosstalk between BER and c-NHEJ repair pathway is mediated by Polb and Ku70.FASEB J2019 Nov;33(11):11668-11681(影响因子5.8)

全文链接:https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.201900308R

成果报道:http://sky.njnu.edu.cn/info/1073/4922.htm

31. Hong Zhu, Congye Wu, Ting Wu, Wen Xia, Shusheng Ci, Weiru He, Yilan Zhang, Lulu Li, Shiying Zhou, Jing Zhang, Ashlin M. Edick, Anna Zhang, Fei-Yan Pan, Zhigang Hu, Lingfeng He*,GUO Z(郭志刚)*. Inhibition of AKT sensitizes cancer cells to antineoplastic drugs by down-regulating Flap Endonuclease 1.Molecular Cancer Therapeutics2019 Dec;18(12):2407-2420 (影响因子6.0)

全文链接:https://doi.org/10.1158/1535-7163.MCT-18-1215

成果报道:http://sky.njnu.edu.cn/info/1073/4925.htm

32. Xiaoli Xu, Rongyi Shi, Li Zheng,GUO Z(郭志刚), Liangyan Wang, Mian Zhou, Ye Zhao, Bing Tian, Khue Truong, Yuan Chen, Binghui Shen *, Yuejin Hua*, Hong Xu*. SUMO-1 modification of FEN1 facilitates its interaction with Rad9-Rad1-Hus1 to counteract DNA replication stress.Journal of Molecular Cell Biology, (5):5, 2018.(影响因子8.1)

全文链接:https://doi.org/10.1093/jmcb/mjy047

33. LingfengHe,HongZhu,Shiying Zhou, Huan Wu, Huan Yang, Huiwen Mao, Feiyan Pan, Zhigang Hu, GUO Z(郭志刚)*. Wnt pathway is involved in 5-FUdrug resistance of colorectal cancer cells. Experimental & Molecular Medicine(2018) 50 (8) :101(影响因子12.1)

全文链接:https://www.nature.com/articles/s12276-018-0128-8

34. Xiang Cao , Yi Zhou , Hongfang Sun, Miao Xu , Xiaowen Bi , Zhihuizhao , Binghui Shen , Fengyi Wan d, ZhuanHonge, Lei Lan*, Lan Luo*,GUO Z(郭志刚)*, Zhimin Yin*. EGFR-TKI-induced HSP70 degradation and BER suppression facilitate the occurrence of the EGFR T790M resistant mutation in lung cancer cells.Cancer Letters424 (2018) 84-96(影响因子9.7)

全文链接:https://doi.org/10.1016/j.canlet.2018.03.004

成果报道:http://sky.njnu.edu.cn/info/1033/2514.htm

35. Sihui Li, Shafat Ali, Xiaotao Duan, Songbai Liu, Juan Du, Changwei Liu, Huifang Dai, Mian Zhou, Lina Zhou, Lu Yang, Peiguo Chu, Ling Li, Ravi Bhatia, Dustin E. Schones, Xiwei Wu, Hong Xu, Yuejin Hua,GUO Z(郭志刚),Yanzhong Yang, Li Zheng* and Binghui Shen JMJD1B Demethylates H4R3me2s and H3K9me2 to Facilitate Gene Expression for Development of Hematopoietic Stem and Progenitor Cells.Cell Reports (2018) 23, 389–403(影响因子9.9)

全文链接:https://doi.org/10.1016/j.celrep.2018.03.051

36. Lingfeng He, Huan Yang Shiying Zhou, Hong Zhu Huiwen Mao, Zhuang Ma,Ting Wu, Alagamuthu Karthick Kumar , handrasekharKathera, AvilalaJanardhan,Feiyan Pan, Zhigang Hu, Yanhua Yang, Libo Luo,GUO Z*(郭志刚). Synergistic antitumor effect of combined paclitaxel with FEN1 inhibitor in cervical cancer cells.DNA Repair63 (2018) 1–9.(影响因子4.3)

全文链接:https://doi.org/10.1016/j.dnarep.2018.01.003

37. Hongfang Sun, Lingfeng He, Huan Wu,Feiyan Pan,Xuping Wu,Jing Zhao, Zhigang Hu,Chandra Sekhar, Hongzhi Li, Li Zheng, Haoyan Chen*,BinghuiShen*,GUO Z(郭志刚)* The FEN1 L209P mutation interferes withlong patch base excision repair and induces cellular transformation.Oncogene(2017) 36, 194–207.(影响因子8.7)

全文链接:https://www.nature.com/articles/onc2016188

38. Lingfeng He, Hong Zhu, Huan Yang, Huan Wu, Hongfang Sun, Feng Jiang, Chandra Sekhar Kathera, Yilan Zhang1, Haoyan Chen, Feiyan Pan, Zhigang Hu,GUO Z(郭志刚)* . FEN1 Promotes Tumor Progress and Confers Cisplatin Resistance in non-small cell Lung Cancer.Molecular Oncology 11 (2017) 640–654.(影响因子7.4)

全文链接:https://doi.org/10.1002/1878-0261.12058

成果报道:http://www.njnu.edu.cn/info/1038/7974.htm

39. Lingfeng He , Yilan Zhang , Hongfang Sun, Feng Jiang, Huan Yang , Huan Wu , Ting Zhou , Sencai Hu , Chandra Sekhar Kathera , Xiaojun Wang , Haoyan Chen , Hongzhi Li, Binghui Shen, Yongqiang Zhu ,GUO Z(郭志刚)* .Targeting DNA Flap Endonuclease 1 to Impede Breast Cancer Progression.EBioMedicine14 (2016) 32–43.(影响因子11.2)

全文链接:https://doi.org/10.1016/j.ebiom.2016.11.012

40. Zhou X, Zhuang Z, Wang W, He L, Wu H, Cao Y, Pan F, Zhao J, Hu Z, Sekhar C, GUO Z(郭志刚)* OGG1 is essential in oxidative stress induced DNA demethylation.Cellular Signalling28 (2016) 1163–1171(影响因子4.8)

全文链接:https://doi.org/10.1016/j.cellsig.2016.05.021

41. Cao Y, Yang H, Zhou X, Mao H, Gao T, Hu Z, He L, Pan F,GUO Z(郭志刚)* . Selection and characterization of human PCSK9 antibody from phage displayed antibody library.Biochemical and Biophysical Research Communications463 (2015) 712e718(影响因子3.3)

全文链接:https://doi.org/10.1016/j.bbrc.2015.05.129

42. GUO Z(郭志刚), Julie Kanjanapangka, Na Liu, Songbai Liu, Changwei Liu, Zhenxing Wu, Yingjie Wang, Tiffany Loh, Claudia Kowolik, JoonasJamsen, Mian Zhou, Khue Truong, Yuan Chen, Li Zheng, Binghui Shen*. Sequential Posttranslational Modifications Program FEN1 Degradation during Cell-Cycle Progression.Molecular Cell(2012) 47, 444–456.(影响因子19.3)

全文链接:https://doi.org/10.1016/j.molcel.2012.05.042

专家评论:https://www.cell.com/action/showPdf?pii=S1097-2765%2812%2900643-0

43. GUO Z(郭志刚),Li Zheng, Hong Xu, Huifang Dai, Mian Zhou, Mary Rose Pascua, Qin M. Chen, and Binghui Shen* 2010. Methylation of FEN1 suppresses nearby phosphorylation and facilitates PCNA binding.Nature Chemical Biology(2010) 6: 766-773.(影响因子16.1)

全文链接:https://www.nature.com/articles/nchembio.422

专家评论:https://www.nature.com/articles/nchembio.444

44. GUO Z(郭志刚),Z. Li, H. Dai, M. Zhou, H. Xu, and B. Shen*. Human DNA Pol β polymorphism, Arg137Gln, impairs Pol β polymerase activity, interaction with PCNA, and base excision repair capacity.Nucleic Acids Research(2009) 37: 3431-3441(影响因子19.1)

全文链接:https://doi.org/10.1093/nar/gkp201

45. L Chung, D Onyango,GUO Z(郭志刚)(共同第一), P Jia, H Dai, S Liu, M Zhou, W Lin, L Zheng, J Lopes, A Nicolas, W Chai, D Raz, KL Reckamp and B Shen* .The FEN1 E359K germline mutation disrupts the FEN1–WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers.Oncogene(2015) 34, 902–911(影响因子8.7)

全文链接:https://www.nature.com/articles/onc201419

46. Li Zheng, Huifang Dai, Mian Zhou, Xiaojin Li, Changwei Liu,GUO Z(郭志刚), Xiwei Wu, Jun Wu, Charles Wang, John Zhong, Qin Huang, Julio Garcia-Aguilar, Gerd P. Pfeifer,Binghui Shen*. Polyploid cells rewire DNA damage response networks to overcome replication stress-induced barriers for tumour progression.Nature Communications(2012),doi:10.1038/ncomms1825(影响因子17.69)

全文链接:https://www.nature.com/articles/ncomms1825

47. Li Zheng,JiaJia,L. David Finger,GUO Z(郭志刚), Cindy Zer, and Binghui Shen*. Functional regulation of FEN1 nuclease and its link to cancer.Nucleic Acids Res. 2011 Feb; 39(3): 781–794.(影响因子19.1)

全文链接:https://doi.org/10.1093/nar/gkq884

48. Li Zheng, Huifang Dai, Muralidhar L Hegde, Mian Zhou,GUO Z(郭志刚), Xiwei Wu, Jun Wu, Lei Su, XueyanZhong, SankarMitra, Qin Huang, Kemp H Kernstine, Gerd P Pfeifer and Binghui Shen*. Fen1 mutations that specifically disrupt its interaction with PCNA cause aneuploidy-associated cancer.Cell Research(2011) 21:1052-1067.(影响因子46.29)

全文链接:https://www.nature.com/articles/cr201135

49. GUO Z(郭志刚), V. Chavez, P. Singh, L. D. Finger, H. Hang, M. L. Hegde, and B. Shen. Comprehensive mapping of the C-terminus of flap endonuclease-1 reveals distinct interaction sites for five proteins that represent different DNA replication and repair pathways.Journal of Molecular Biology(2008) 377:679-90.(影响因子6.1)

全文链接:https://doi.org/10.1016/j.jmb.2007.10.074

50. GUO Z(郭志刚), L. Qian, R. Liu, H. Dai, M. Zhou, L. Zheng, and B. Shen. Nucleolar localization and dynamic roles of flap endonuclease 1 in ribosomal DNA replication and damage repair.Molecular and Cellular Biology(2008) 28:4310-9.(影响因子5.06)

全文链接:https://doi.org/10.1128/MCB.00200-08

51. Li Zheng, Mian Zhou,GUO Z(郭志刚), Huiming Lu, Limin Qian, Huifang Dai, JunzhuanQiu, Elena Yakubovskaya, Daniel F. Bogenhagen, Bruce Demple, Binghui Shen. Human DNA2 Is a Mitochondrial Nuclease/Helicase for Efficient Processing of DNA Replication and Repair Intermediates.Molecular cell(2008) 32(3):325–336(影响因子19.3)

全文链接:https://doi.org/10.1016/j.molcel.2008.09.024

52. Muralidhar L. Hegde, Corey A. Theriot, Aditi Das, Pavana M. Hegde, GUO Z(郭志刚),Ronald K. Gary ,Binghui Shen and SankarMitra. Physical and Functional Interaction between Human Oxidized Base-specific DNA Glycosylase NEIL1 and Flap Endonuclease 1.Journal of Biological Chemistry,283, 27028-27037.(影响因子5.4)

全文链接:https://doi.org/10.1074/jbc.M802712200

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