科研学者

武远众

职称:博士、副研究员、硕士生导师

专长

蛋白翻译后修饰与稳态调控

职称:博士、副研究员、硕士生导师
专长:蛋白翻译后修饰与稳态调控
招生专业:分子医学
Email:  wuyzh@sysucc.org.cn

成果介绍:
  蛋白翻译后修饰及稳态异常可引起细胞周期失调、表观遗传紊乱,导致肿瘤发生发展。围绕该科学问题开展系列原创性研究,开发了2个研究工具:蛋白稳定性调控因子筛选系统ProSRSA(Protein Stability Regulators Screening Assay)、内含子标记辅助基因敲入系统GEIS(Gene Editing through an Intronic Selection marker)。取得如下科学发现:(1)揭示乙酰转移酶KAT8与转录因子IRF1发生相分离,KAT8同时催化IRF1 K78、H4K16乙酰化以激活PD-L1转录,并研发阻断KAT8-IRF1相分离的抗肿瘤多肽;(2)系统性阐明乙酰化、SUMO化修饰可增强单链DNA结合蛋白hSSB1的蛋白稳态,进而稳定p53激活细胞周期检查点及促进DNA损伤修复,为hSSB1作为肿瘤放化疗增敏新靶点提供了实验证据;(3)揭示细胞周期检查点激酶Chk1/2磷酸化RBM28促进其核仁至核浆转位,核浆RBM28可多价结合p53抑制其转录活性,建立核仁应激与细胞周期串话机制,拓展了Chk1/2抑制剂临床应用。相关研究成果以通讯/第一作者(含共同)发表于Nat Cancer, Nat Commun, Nucleic Acids Res, Cell Res, Cell Discov, J Biol Chem, Cell Mol Life Sci,Signal Transduct Target Ther, Oncogene等高水平期刊。获授权专利2项,主持国家自然科学基金面上项目2项,受邀为中国科学院生物化学与生物物理学报撰写综述(封面发表),受邀在2019年全国肿瘤细胞生物学年会作学术报告。

教育背景和工作经历:
2021/02-至今,中山大学,肿瘤防治中心,副研究员
2015/08-2021/02,中山大学,肿瘤防治中心,助理研究员
2010/09–2015/07,中山大学,分子医学,博士,导师:康铁邦 
2006/09–2010/07,中山大学,生物技术,学士

代表性论文:
(1)Yuanzhong Wu #, Liwen Zhou #, Yezi Zou, Yijun Zhang, Meifang Zhang, Liping Xu, Lisi Zheng, Wenting He, Kuai Yu, Ting Li, Xia Zhang, Zhenxuan Chen, Ruhua Zhang, Penghu i Zhou, Nu Zhang, Limin Zheng, and Tiebang Kang *;Disrupting KAT8-IRF1 condensates diminishes PD-L1 expression and promotes antitumor immunity,Nature Cancer, 2023 Mar;4(3):382-400
(2)Lin, Xin#; Zhou, Liwen#; Zhong, Jianliang; Zhong, Li; Zhang, Ruhua; Kang, Tiebang*; Yuanzhong Wu*;RNA-binding protein RBM28 can translocate from the nucleolus to the nucleoplasm to inhibitthe transcriptional activity of p53., Journal of Biological Chemistry, 2022 Feb;298(2):101524. 
(3)Wang, Shang#; Li, Yuqing#; Zhong, Li#; Wu, Kai; Zhang, Ruhua; Kang, Tiebang; Wu, Song*; Yuanzhong Wu*;Efficient gene editing through an intronic selection marker in cells., Cellular and Molecular Life Sciences, 2022 Jan 31;79(2):111
(4)Xin Wang#, Ge Qin#, Xiaoting Liang, Wen Wang, Zhuo Wang, Dan Liao, Li Zhong, Ruhua Zhang, Yi-Xin Zeng, Yuanzhong Wu*,Tiebang Kang*. Targeting the CK1α/CBX4 axis for metastasis in osteosarcoma. Nature Communications,28 Feb 2020,volume 11, Article number: 1141.
(5)Liwen Zhou#, Lisi Zheng#, Kaishun Hu#, Xin Wang, Ruhua Zhang, Yezi Zou, Li Zhong, Shang Wang, Yuanzhong Wu*,Tiebang Kang*. SUMOylation stabilizes hSSB1 and enhances the recruitment of NBS1 to DNA damage sites. Signal Transduction and Targeted Therapy. 2020 Jun 24;5(1):80. 
(6)Yuanzhong Wu#, Liwen Zhou#, Zifeng Wang, Xin Wang, Ruhua Zhang, Lisi Zheng, Tiebang Kang*. Systematic screening for potential therapeutic targets in osteosarcoma through a kinome-wide CRISPR-Cas9 library. Cancer Biol Med. 2020 Aug 15;17(3):782-794.
(7)Yuanzhong Wu, Liwen Zhou, Xin Wang, Jinping Lu, Ruhua Zhang, Xiaoting Liang, Li Wang, Wuguo Deng, Yi-xin Zeng, Tiebang Kang*. A genome-scale CRISPR-Cas9 screening method for protein stability reveals novel regulators of Cdc25A. Cell Discovery. 2016 May 24;2:16014. 
(8)Yuanzhong Wu#, Hongxia Chen#, Jinping Lu, Meifang Zhang, Ruhua Zhang, Tingmei Duan, Xin Wang, Jun Huang*, Tiebang Kang*. Acetylation dependent function of human single-strand DNA binding proteins 1. Nucleic Acids Research. 2015 Sep 18;43(16):7878-87. 
(9)Yuanzhong Wu, Jinping Lu, Tiebang Kang. Human single-stranded DNA binding proteins: guardians of genome stability. Acta Biochim Biophys Sin. 2016 Jul; 48(7):671-7 
(10)Shuangbing Xu#, Yuanzhong Wu#, Qiong Chen, Jingying Cao, Kaishun Hu, Jianjun Tang, Yi Sang, Fenju Lai, Li Wang, Ruhua Zhang, Sheng ping Li, Yixin Zeng, Yuxin Yin, Tiebang Kang*. hSSB1 regulates both the stability and the transcriptional activity of p53. Cell Research. 2013 Mar;23(3):423-35. 

专利:
(1)一种用于抑制细胞PD-L1表达的多肽及其应用,ZL201910185978.2,2021-1-1授权
(2)一种CRISPR-Cas9介导的外显子定点突变技术在细胞系中应用,ZL201910302026.4,2021-3-30授权
(3)基于CRISPR-dCas9的基因靶向去甲基化方法及其应用,2022106396990,实质性审查
 

 

 

 

 

更新时间:2023年4月17日