福利姬

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：福利姬 （双聘），副教授

2021.10~至今：福利姬 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。

1. 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

2. 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；

3. 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。

4. 国家自然科学基金委员会，国家海外高层次人才引进计划，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

10. Zebin Tong#, Xiangwei Wu#, Hongyi Cai#, Shidian Wu, Tianyi Zhang, Zhiheng Deng, Ziyu Xu, Rujing Yuan, Huasong Ai*, Lei Liu* &Man Pan*. Structural basis for the ubiquitin E4 enzyme Ufd2-catalyzed K48/K29 branched ubiquitin chains. Nature Chemical Biology, 2025, Accepted in principle.

9. Xiangwei Wu#, Huasong Ai#, Junxiong Mao#, Hongyi Cai, Lu-Jun Liang, Zebin Tong, Zhiheng Deng, Qingyun Zheng*, Lei Liu* & Man Pan*. Structural visualization of HECT-type E3 ligase Ufd4 accepting and transferring ubiquitin to form K29/K48-branched polyubiquitination. Nature Communications, 2025, 16, 4313.

8. Jibin Cui#, Qingyun Zheng#, Yicheng Weng#, Xiaoguo Zhai, Zhen Su, Yunxiang Du, Xiaoxiong Wei, Yuyuan Yu*, Qian Qu*, Man Pan*. Structure-guided development of chemically tailored peptide binders of RNF43/ZNRF3 to enable versatile design of membrane protein-targeting PROTACs,  Angewandte Chemie International Edition, 2025, e202501488. 10.1002/anie.202501488

7. 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

6. 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, //doi.org/10.1038/s41594-024-01342-2. 

5. 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.

3. 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.

2. 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.   

1. 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.  

2024 中国化学会青年化学奖

2023 中国国际多肽会议青年多肽科学家奖

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博士后

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