电子邮件:panman@sjtu.edu.cn
通讯地址:上海市闵行区东川路800号转化医学大楼E416
个人主页: https://www.x-mol.com/groups/panlab
2012.08-2017.07 清华大学,生物学,博士,导师: 刘磊 教授
2008.09-2012.07 山东大学(威海),药学,学士
2022.10~至今:上海交通大学化学化工学院(双聘),副教授
2021.10~至今:上海交通大学转化医学研究院,长聘教轨副教授
2017.09~2021.09:芝加哥大学生物化学与分子生物系,博士后
蛋白质翻译后修饰—泛素化修饰—直接调控了细胞内几乎所有蛋白的稳态。简单来说,蛋白底物可以由泛素E1、E2、E3酶级联催化完成泛素化修饰,随后被蛋白质机器(诸如proteasome、p97)识别并降解处理。近年来通过药物设计来靶向泛素化修饰POI蛋白,以实现其快速降解(Targeted protein degradation)的策略,被证明可以实现疾病诊疗并广泛用于新药研发。
课题组致力于通过化学生物学交叉技术,包括蛋白合成化学、蛋白探针组学、冷冻电镜等技术,发掘新型蛋白稳态调控过程,解析蛋白稳态调控过程的关键酶促分子机制,并期望推动新型靶向蛋白稳态类药物研发。具体展开方向如下:
· 开发设计新型泛素修饰蛋白探针,运用探针工具解析泛素化修饰调控蛋白稳态的关键酶促分子机制,并基于机制理性设计新型靶向蛋白稳态的方法策略;
· 发展精准泛素修饰蛋白获取方法,用于新型蛋白稳态调控过程发掘,为蛋白稳态调控药物分子开发提供新赛道。
上海市科学技术委员会,基础研究特区计划,基于化学生物学策略的泛素E3酶功能机制解析及应用,2022-11至2026-10,主持,在研
国自然基金委面上项目,22277073,用于解析p97机制的蛋白化学泛素化新策略,2023-2026, 主持,在研;
上海市科学技术委员会,启明星计划项目,II型降解子的泛素化机制及PROTAC分子开发,2022-07至2025-06,主持,在研。
国家自然科学基金委员会,优秀青年科学基金项目(海外),泛素蛋白质机器的功能机制与化学调控,2022-01至2024-12,主持,在研。
独立PI期间
1. Huasong Ai#, Zebin Tong#, Zhiheng Deng#, Qiang Shi, Shixian Tao, Gaoge Sun, Jiawei Liang, Maoshen Sun, Xiangwei Wu, Qingyun Zheng, Lujun Liang, Hang Yin, Jia-Bin Li, Shuai Gao, Changlin Tian*, Lei Liu* & Man Pan*. Mechanism of nucleosomal H2A K13/15 monoubiquitination and adjacent dual monoubiquitination by RNF168. Nature Chemical Biology, 2024, 10.1038/s41589-024-01750-x
2. Huasong Ai#, Zaozhen He#, Zhiheng Deng, Guo-Chao Chu, Qiang Shi, Zebin Tong, Jia-Bin Li, Man Pan*, Lei Liu*. Structural and mechanistic basis for nucleosomal H2AK119 deubiquitination by single-subunit deubiquitinase USP16. Nature Structural & Molecular Biology, 2024, https://doi.org/10.1038/s41594-024-01342-2.
3. Xiangwei Wu#, Yunxiang Du#, Lu-Jun Liang#, Ruichao Ding, Tianyi Zhang, Hongyi Cai, Xiaolin Tian, Man Pan* & Lei Liu*. Structure-Guided Engineering Enables E3 Ligase-Free and Versatile Protein Ubiquitination via UBE2E1. Nature Communications, 2024, 15, 1266.
4. Zebin Tong#, Huasong Ai#,*, Ziyu Xu#, Kezhang He#, Guo-Chao Chu, Qiang Shi, Zhiheng Deng, Qiaomei Xue, Maoshen Sun, Yunxiang Du, Lujun Liang, Jia-Bin Li, Man Pan* & Lei Liu*. Synovial sarcoma X breakpoint 1 protein uses a cryptic groove to selectively recognize H2AK119Ub nucleosomes. Nature Structural & Molecular Biology, 2024, 31, 300-310.
5. Zhiheng Deng#, Huasong Ai#, Maoshen Sun#, Zebin Tong#, Yunxiang Du#, Qian Qu, Liying Zhang, Ziyu Xu, Shixian Tao, Qiang Shi, Jia-Bin Li, Man Pan, Lei Liu*. Mechanistic insights into nucleosomal H2B monoubiquitylation mediated by yeast Bre1-Rad6 and its human homolog RNF20/RNF40-hRAD6A. Molecular Cell, 2023, doi.org/10.1016/j.molcel.2023.08.001.
6. Huasong Ai#, Zebin Tong#, Zhiheng Deng, Jiakun Tian, Liying Zhang, Maoshen Sun, Yunxiang Du, Ziyu Xu, Qiang Shi, Lujun Liang, Qingyun Zheng, Jia-Bin Li, Man Pan*, Lei Liu*. Synthetic E2-Ub-nucleosome conjugates for studying nucleosome ubiquitination. Chem, 2023, 10.1016/j.chempr.2023.01.012.
7. Qingyun Zheng#; Tian Wang#; Junxiong Mao#; Guochao Chu; Lujun Liang; Yangwode Jing; Chong Zuo; Yuanyuan Yu; Honggang Hu*; Man Pan*; A bifunctional molecule-assisted synthesis of mimics for use in probing the ubiquitination system. Nature Protocols, 2022, doi.org/10.1038/s41596-022-00761-z.
博士-博后期间
1. Man Pan#*; Qingyun Zheng#; Tian Wang#; Lujun Liang#; Chong Zuo; Ruichao Ding; Huasong Ai; Yuan Xie; Si Dong; Yuanyuan Yu*; Lei Liu*; Minglei Zhao*; Structural Insights Into the Initiation and Elongation of Ubiquitination by Ubr1, Nature, 2021, 600, 334–338.
2. Man Pan#*; Yuanyuan Yu#; Huasong Ai; Qingyun Zheng; Yuan Xie; Lei Liu*; Minglei Zhao*; Mechanistic insight into substrate processing and allosteric inhibition of human p97, Nature Structural & Molecular Biology, 2021, 28, 614-625.
3. Man Pan#; Qingyun Zheng#; Yuanyuan Yu#; Huasong Ai; Yuan Xie; Xin Zeng; Chu Wang; Lei Liu*; Minglei Zhao*; Seesaw conformations of Npl4 in the human p97 complex and the inhibitory mechanism of a disulfiram derivative, Nature Communications, 2021, 12(1): 121.
4. Man Pan#; Qingyun Zheng#; Shan Ding#; Lujia Zhang#; Qian Qu; Tian Wang; Danning Hong; Yujing Ren; Lujun Liang; Chunlai Chen*; Ziqing Mei*; Lei Liu*; Chemical Protein Synthesis Enabled Mechanistic Studies on the Molecular Recognition of K27-linked Ubiquitin Chains, Angewandte Chemie International Edition, 2019, 9(58): 2627-2631.
5. Man Pan#; Shuai Gao#; Yong Zheng#; Xiaodan Tan; Huan Lan; Xianglong Tan; Demeng Sun; Lining Lu; Tian Wang; Qingyun Zheng; Yichao Huang; Jiawei Wang; Lei Liu*; Quasi-Racemic X-ray Structures of K27-Linked Ubiquitin Chains Prepared by Total Chemical Synthesis, Journal of the American Chemical Society, 2016, 23(138): 7429-7435.
6. Man Pan#; Shan Li#; Xiang Li; Feng Shao; Lei Liu*; Honggang Hu*; Synthesis of and specific antibody generation for glycopeptides with arginine N-GlcNAcylation, Angewandte Chemie International Edition, 2014, 53(52): 14517-21.
7. Man Pan#; Qingyun Zheng#; Shuai Gao; Qian Qu; Yuanyuan Yu; Ming Wu; Huan Lan; Yulei Li; Sanling Liu; Jiabin Li; Demeng Sun; Lining Lu; Tian Wang; Wenhao Zhang; Jiawei Wang; Yiming Li; Hong-Gang Hu*; Changlin Tian*; Lei Liu*; Chemical Synthesis of Structurally Defined Phosphorylated Ubiquitins Suggests Impaired Parkin Activation by Phosphorylated Ubiquitins with a Non-Phosphorylated Distal Unit, CCS Chemistry, 2019, 1: 476-489.
8. Yuanyuan Yu#; Qingyun Zheng#; Satchal K. Erramilli#; Man Pan#*; Seongjin Park; Yuan Xie; Jingxian Li; Jingyi Fei; Anthony A. Kossiakoff*; Lei Liu*; Minglei Zhao*; K29-Linked Ubiquitin Signaling Regulates Proteotoxic Stress Response and Cell Cycle, Nature Chemical Biology, 2021, 17: 896–905.
9. Guo-Chao Chu#; Man Pan#; Jiabin Li#; Sanling Liu; Chong Zuo; Ze-Bin Tong; Jing-Si Bai; Qingyue Gong; Huasong Ai; Jian Fan; Xianbin Meng; Yi-Chao Huang; Jing Shi; Haiteng Deng; Changlin Tian*; Yi-Ming Li*; Lei Liu*; Cysteine-Aminoethylation-Assisted Chemical Ubiquitination of Recombinant Histones, Journal of the American Chemical Society, 2019, 141: 3654-3663.
10. Qian Qu#; Man Pan#; Shuai Gao; Qing-Yun Zheng; Yuan-Yuan Yu; Jia-Can Su; Xiang Li; Hong-Gang Hu*; A Highly Efficient Synthesis of Polyubiquitin Chains, Advanced Science, 2018, 5: 1800234.
11. Qingyun Zheng#; Tian Wang#; Guochao Chu#; Chong Zuo; Rui Zhao; Xin Sui; Linzhi Ye; Yuanyuan Yu; Jingnan Chen; Xiangwei Wu; Wenhao Zhang; Haiteng Deng; Jing Shi; Man Pan*; Yiming Li*; Lei Liu*; An E1-Catalyzed Chemoenzymatic Strategy to Isopeptide-N-Ethylated Deubiquitylase-Resistant Ubiquitin Probes, Angewandte Chemie International Edition, 2020, 59(32): 13496-13501.
12. Shuai Gao#; Man Pan#; Yong Zheng#; Yichao Huang; Qingyun Zheng; Demeng Sun; Lining Lu; Xiaodan Tan; Xianglong Tan; Huan Lan; Jiaxing Wang; Tian Wang; Jiawei Wang*; Lei Liu*; Monomer/Oligomer Quasi-Racemic Protein Crystallography, Journal of the American Chemical Society, 2016, 43(138): 14497-14502.
13. Man Pan#; Yao He#; Ming Wen; Fangming Wu; Demeng Sun; Sijian Li; Longhua Zhang; Yiming Li; Changlin Tian*; One-pot hydrazide-based native chemical ligation for efficient chemical synthesis and structure determination of toxin Mambalgin-1, Chemical Communications, 2014, 50(44): 5839.
14. Demeng Sun#; You Yu#; Xiaobin Xue#; Man Pan#; Ming Wen; Siyu Li; Qian Qu; Xiaorun Li; Longhua Zhang; Xueming Li; Lei Liu*; Maojun Yang*; Changlin Tian*; Cryo-EM structure of the ASIC1a–mambalgin-1 complex reveals that the peptide toxin mambalgin-1 inhibits acid-sensing ion channels through an unusual allosteric effect, Cell Discovery, 2018, 4(1): 27.
我们正在寻找各个阶段充满活力和热情的研究人员加入我们的团队!
博士后
欢迎具有化学、生物学和药学背景的博士毕业生加入我们。
研究生
欢迎具有化学、生物学和药学背景的本科毕业生和硕士毕业生申请者!
本科生
实验室可以提供多肽合成化学、基础分子生物学、结构生物学训练,欢迎有意向的本科同学申请。
感兴趣的同学请将您的简历发送至 panman@sjtu.edu.cn。