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蛋白降解和癌症生物学

课题组长

姓名：

仓勇教授研究员博士生导师, PhD, 教授

职务：

所在院所：

87978797威尼斯老品牌

荣誉称号：

教育经历：

1988/09—1992/07，复旦大学，学士
1995/08—1996/07，美国德州大学健康科学中心，博士研究生
1996/08—2001/11，美国爱因斯坦医学院，博士

博士后及工作经历：

2001/12—2007/06，美国哥伦比亚大学，博士后
2007/07—2011/12，美国加州伯罕医学研究所，助理教授
2010/05—2017/10，浙江大学，教授
2017/11—2021/12，87978797威尼斯老品牌，87978797威尼斯老品牌，副教授（TENURE-TRACK）
2021/12—至今，87978797威尼斯老品牌，87978797威尼斯老品牌，教授（TENURED）

课题组简介

研究方向：

蛋白降解；分子胶；靶向和免疫治疗

研究内容：

实验室利用分子生物学手段和细胞/ 小鼠模型来研究蛋白泛素化降解调控及其在发育和疾病生成中的作用, 同时也探索小分子化合物劫持泛素连接酶用于治疗癌症和调节免疫功能的机制。具体有两个方向的研究：

1. 靶向蛋白降解的新型分子胶水化合物的发现及其在癌症治疗领域的应用。

2. 用遗传和化学手段研究T细胞控制癌症细胞生长和转移的机制。

课题组网站：

研究成果展示

Cancer is a leading cause of human death. Cancer arises when somatic mutations override intracellular and immunological control of cell proliferation. The ultimate goal of my laboratory research is to exploit the vulnerability of cancer and develop novel therapeutics stopping the uncontrolled growth and spreading of cancer cells. Our therapeutic development is built upon my 20 years of research expertise in the biology of the Cullin Ring Ligase 4 (CRL4) ubiquitin ligase, particularly CRL4^CRBN, and its application to targeted protein degradation. We have designed CRBN-engaging chemical libraries and screened for novel molecular glue-type degraders of cancer-driving oncoproteins, thus providing a new discovery modality to expand current oncology drug pipelines. Meanwhile, we have developed mouse models to investigate the mechanism underlying the anti-tumor immunity of lenalidomide and its analogues, which have recently been established as molecular glues to redirect CRBN for their clinical effectiveness. Our early success in this field has led us to examine genetic mutations that control cancer sensitivity to T cell-mediated cytotoxicity. Using customized CRISPR-Cas9 library screening in various tumor models, we have identified several pathways that modulate tumor growth by regulating tumor infiltrating lymphocytes, in a manner dependent or independent on the PD-1 immune checkpoint. Given the interdisciplinary and translational nature of our work, we closely collaborate with synthetic and medicinal chemists as well as computational and structural biologists.

本实验室近年来上发表了一系列CRL4 泛素连接酶通过对不同底物的泛素化从而调控发育和疾病，同时阐明CRL4 其本身被激活的机制。特别是基于CRL4底物受体蛋白CRBN的研究，起始了实验室用新型分子胶水化合物降解癌症相关蛋白降解的探索。可扫下面二维码进入介绍实验室分子胶水研究的科普讲座。

代表性论文（*第一作者，#通讯作者）

1.Song, Tian-Yu*; Long, Min*; Zhao, Hai-Xin*; Zou, Miao-Wen; Fan, Hong-Jie; Liu, Yang; Geng, Chen-Lu; Song, Min-Fang; Liu, Yu-Feng; Chen, Jun-Yi; Yang, Yu-Lin; Zhou, Wen-Rong; Huang, Da-Wei; Peng, Bo; Peng, Zhen-Gang; Cang, Yong^#.Tumor evolution selectively inactivates the core microRNA machinery for immune evasion.NATURE COMMUNICATIONS. 2021. 12(1).
2.Liu, Jiye*; Hideshima, Teru; Xing, Lijie; Wang, Su; Zhou, Wenrong; Samur, Mehmet K.; Sewastianik, Tomasz; Ogiya, Daisuke; An, Gang; Gao, Shaobing; Yang, Li; Ji, Tong; Bianchi, Giada; Wen, Kenneth; Tai, Yu-Tzu; Munshi, Nikhil; Richardson, Paul; Carrasco, Ruben; Cang, Yong; Anderson, Kenneth C..ERK signaling mediates resistance to immunomodulatory drugs in the bone marrow microenvironment.SCIENCE ADVANCES. 2021. 7(23).
3.Hou, Lidan*; Zhao, Jie; Gao, Shaobing; Ji, Tong; Song, Tianyu; Li, Yining; Wang, Jingjie; Geng, Chenlu; Long, Min; Chen, Jiang; Lin, Hui; Cai, Xiujun; Cang, Yong^#.Restriction of hepatitis B virus replication by c-Abl-induced proteasomal degradation of the viral polymerase.SCIENCE ADVANCES. Feb 2019. 5(2).
4.Liu, Jiye*; Song, Tianyu*; Zhou, Wenrong*; Xing, Lijie; Wang, Su; Ho, Matthew; Peng, Zhengang; Tai, Yu-Tzu; Hideshima, Teru; Anderson, Kenneth C.^#; Cang, Yong^#.A genome-scale CRISPR-Cas9 screening in myeloma cells identifies regulators of immunomodulatory drug sensitivity.LEUKEMIA. Jan 2019. 33(1):171-180.
5.Song, Tianyu*; Liang, Shenghui; Liu, Jiye; Zhang, Tingyue; Yin, Yifei; Geng, Chenlu; Gao, Shaobing; Feng, Yan; Xu, Hao; Guo, Dongqing; Roberts, Amanda; Gu, Yuchun^#; Cang, Yong^#.CRL4 antagonizes SCFFbxo7-mediated turnover of cereblon and BK channel to regulate learning and memory.PLOS GENETICS. Jan 2018. 14(1).
6.Li, Gaofeng*; Ji, Tong; Chen, Jiang; Fu, Yufei; Hou, Lidan; Feng, Yan; Zhang, Tingyue; Song, Tianyu; Zhao, Jie; Endo, Yoko; Lin, Hui; Cai, Xiujun^#; Cang, Yong^#.CRL4(DCAF8) Ubiquitin Ligase Targets Histone H3K79 and Promotes H3K9 Methylation in the Liver.CELL REPORTS. 2017. 18(6):1499-1511.
7.Gao, Shaobing*; Geng, Chenlu; Song, Tianyu; Lin, Xuanru; Liu, Jiye; Cai, Zhen; Cang, Yong^#.Activation of c-Abl Kinase Potentiates the Anti-myeloma Drug Lenalidomide by Promoting DDA1 Protein Recruitment to the CRL4 Ubiquitin Ligase.JOURNAL OF BIOLOGICAL CHEMISTRY. 2017. 292(9):3683-3691.
8.Jin, Shengfang^#*; Chen, Jiang; Chen, Lizao; Histen, Gavin; Lin, Zhizhong; Gross, Stefan; Hixon, Jeffrey; Chen, Yue; Kung, Charles; Chen, Yiwei; Fu, Yufei; Lu, Yuxuan; Lin, Hui; Cai, Xiujun; Yang, Hua; Cairns, Rob A.; Dorsch, Marion; Su, Shinsan M.; Biller, Scott; Mak, Tak W.^#; Cang, Yong^#.ALDH2(E487K) mutation increases protein turnover and promotes murine hepatocarcinogenesis.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2015. 112(29):9088-9093.
9.Liu, Jiye*; Ye, Jia; Zou, Xiaolong; Xu, Zhenghao; Feng, Yan; Zou, Xianxian; Chen, Zhong; Li, Yuezhou; Cang, Yong^#.CRL4A(CRBN) E3 ubiquitin ligase restricts BK channel activity and prevents epileptogenesis.NATURE COMMUNICATIONS. 2014. 5.
10.Yamaji, Sachie*; Zhang, Mingjun; Zhang, Jing; Endo, Yoko; Bibikova, Elena; Goff, Stephen P.^#; Cang, Yong^#.Hepatocyte-specific deletion of DDB1 induces liver regeneration and tumorigenesis.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2010. 107(51):22237-22242.

专著

专利

项目

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87978797威尼斯老品牌仓勇研究组招聘博后及技术员

导师介绍：利用CRISPR-Cas9基因组文库筛选肿瘤免疫治疗靶点以及研究蛋白泛素化酶如何调控癌症免疫和肿瘤发生的机制.实验室的文章链接:https://www.ncbi.nlm.nih.gov/pubmed/?term=cang+yong

主要项目：

Molecular Glue Discovery项目：molecular glue degrader是一类介导E3与靶点蛋白结合并泛素化降解的新型小分子靶向药物，作为目前药物研发领域的热门，molecular glue degrader 有望为“不可成药”靶点提供可能。项目组前期构建了此类小分子的筛选平台现与罗氏制药合作，致力于开发更多分子胶水类降解剂，探寻其靶点及作用机制。

项目组现招聘实验技术员1名、博士后1名。

一、实验技术员(Technician)

【岗位职责】

1.承担项目的部分常规实验（细胞培养、分子生物学实验等）

2.参与项目汇报和讨论

【应聘条件】

1.已经或者即将取得生物医学相关专业硕士学历

2.良好的沟通协调能力和团队合作精神

二、博士后(Postdoctoral fellow)

【岗位职责】

1.独立承担课题研究

2.协助课题组申请课题、发表文章