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郭志刚

郭志刚

教授、博士生导师、南京师范大学生命科学学院副院长

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

2005年毕业于南京大学,获生物化学与分子生物学博士学位。毕业后加入美国Tanox生物制药公司从事抗体药物研发。之后赴美国希望城国家医学中心从事DNA修复与抗肿瘤研究。20113月入职南京师范大学,受聘教授、博士生导师。现任南京师范大学生命科学学院副院长、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。

 

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

 

荣誉或奖励

辽宁省科技进步二等奖(2019

第五届国家侨界创新贡献奖(2014

14届江苏青年科技奖(2014

11届南京市自然科学优秀论文一等奖(2013

江苏省科协青年创业大赛二等奖(2016

南京师范大学优秀教师奖(2012

 

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。

 

主要研究方向

1 DNA损伤修复与抗肿瘤研究

2)抗体工程及治疗性抗体的开发与应用

3CAR-T与细胞免疫治疗

 

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. 针对PCSK9的全人源抗体可变区基因及其应用;

专利号:ZL 201510205553.5   

  1. 一种人源抗VEGFR2单链抗体及其应用

专利号:ZL201811003017 .7

  1. 抗人PCSK9单克隆抗体及其用途 

专利号:ZL201910073758.0

  1. 一种anti-CD70 CAR-T 细胞制剂及其制备方法与应用。

专利号:ZL201910857176.1

  1. 人CD70抗原结合多肽

专利号:ZL201911052838.4

  1. Small molecule compound and derivative thereof

澳大利亚革新专利,专利号:2020101410

  1. Doxorubicin combined medicine and its application

澳大利亚革新专利,专利号:2020101830

  1. 抗人GPC3单克隆抗体;专利号:ZL201911053957.1
  2. 靶向人CD19的嵌合抗原受体及其应用;

专利号:ZL202010051900.4

  1. 同时靶向BCMA和CD38的嵌合抗原受体及其应用

专利号:ZL202010052549

  1. 抗人MSLN单克隆抗体及其应用

专利号:ZL202010447170.X

 

代表性论文

  1. 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.

 

  1. 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.

 

  1. 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

 

  1. 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.

 

  1. 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.

 

  1. 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

 

  1. 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.

 

  1. 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. Epub 2020 Aug 20. PMID: 32861926.

 

  1. 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). Srcmediated phosphorylation of GAPDH regulates its nuclear localization and cellular response to DNA damage.  FASEB J, 2020, 34(8):10443-10461

 

  1. 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.

 

  1. 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.

 

  1. Jing Zhang,Li Jing, Subee Tan, Er-Ming Zeng, Yingbo Lin, Lingfeng He , Zhigang Hu , Jianping Liu and GUO 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.

 

  1. 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.https://doi.org/10.1016/j.elecom.2020.106808.

 

  1. 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.

 

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

 

  1. 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.

 

  1. 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.

 

  1. XueZeng,XiujuanQu,ChenyangZhao,LuXu,KezuoHou,YunpengLiu,NaZhang,JingFeng,ShaShi,LingyunZhang,iawen Xiao, GUO Z(郭志刚),Yuee Teng, Xiaofang Che*.FEN1 mediates miR200a methylation and promotes breast cancer cell growth via MET and EGFR signaling. The FASEB J, 2019, 33(10).

 

  1. JinLi Li,JianPing Wang,Hong Chang,ShengMing Deng,JiaHui Du,XiaoXiao Wang,HeJuan Hu,DongYin Li,XiangBin Xu,WeiQiang Guo,YaoHua 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.

 

  1. 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

 

  1. 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

 

  1. 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.

 

  1. 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

 

  1. 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 Letters 424 (2018) 84-96

 

  1. 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

 

  1. 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 Repair 63 (2018) 1–9.

 

  1. 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 with long patch base excision repair and induces cellular transformation. Oncogene (2017) 36, 194–207.

 

  1. 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.

 

  1. 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.

 

  1. 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

 

  1. Pan, F.,  Jing ZhaoTing ZhouZhihui KuangHuifang DaiHuan WuHongfang SunXiaolong ZhouXuping WuZhigang HuLingfeng HeBinghui shen, GUO Z(郭志刚)*  . Mutation of DNA Polymeraseβ R137Q Results in Retarded Embryo Development Due to Impaired DNA Base Excision Repair in Mice. Scientific Report, 2016. 6: p. 28614.
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  3. Ting Zhou,Yan Cao, Ying Han, Jing Zhao, HongfangSun,Xiaolong Zhou, XupingWu,Lingfeng He, Zhigang Hu,Haoyan Chen*, Binghuishen*, GUO Z(郭志刚)*  . The DNA Pol β R152C Mutation Impairs Base Excision Repair and Induces Cellular Transformation. Oncotarget 2016 Feb 9; 7(6):6902-15.

 

  1. Cao YYang HZhou XMao HGao THu ZHe LPan F, GUO Z(郭志刚)* . Selection and characterization of human PCSK9 antibody from phage displayed antibody library. Biochemical and Biophysical Research Communications 463 (2015) 712e718

 

  1. 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

 

  1. 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. PfeiferBinghui Shen*.  Polyploid cells rewire DNA damage response networks to overcome replication stress-induced barriers for tumour progression.Nature Communications20123 ,doi:10.1038/ncomms1825

 

  1. Li ZhengJiaJia 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.

 

  1. 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. 

 

  1. 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.

 

  1. 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6.0

 

  1. 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

 

  1. 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.The Journal of Biological Chemistry,283, 27028-27037.