潘漫
博士，长聘教轨副教授，博士生导师
地址: 转化医学中心E416，1929cc威尼斯闵行校区
本科就读于山东大学（威海）药学专业；博士就读于清华大学，主要技术方向为蛋白合成化学；博士后工作于芝加哥大学（University of Chicago），主要技术方向为单颗粒冷冻电镜。2021年10月加入1929cc威尼斯，系上海市海外高层次引进人才，获得优秀青年科学基金（海外）项目、自然科学面上项目，上海市科委启明星项目，上海市科委基础研究特区计划等项目支持。

代表性一作论文：
1. Nature, 2021, 600, 334–338.
Structural Insights Into the Initiation and Elongation of Ubiquitination by Ubr1,
2. Nature Structural & Molecular Biology, 2021, 28, 614-625.
Mechanistic insight into substrate processing and allosteric inhibition of human p97,
3. Nature Communications, 2021, 12(1): 121.
Seesaw conformations of Npl4 in the human p97 complex and the inhibitory mechanism of a disulfiram derivative,
4. Nature Chemical Biology, 2021, 17: 896–905.
K29-Linked Ubiquitin Signaling Regulates Proteotoxic Stress Response and Cell Cycle,

代表性通讯论文：
1. Nature Protocols, 2022, 10.1038/s41596-022-00761-z.
A bifunctional molecule-assisted synthesis of mimics for use in probing the ubiquitination system.
2. Chem 2022, 10.1016/j.chempr.2023.01.012.
Synthetic E2-Ub-nucleosome conjugates for studying nucleosome ubiquitination.
3. Angewandte Chemie International Edition, 2020, 59(32): 13496-13501.
An E1-Catalyzed Chemoenzymatic Strategy to Isopeptide-N-Ethylated Deubiquitylase-Resistant Ubiquitin Probes,

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。
在研项目：
1.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；
2.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。
3.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。
4.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。

加入SJTU后的工作：
1. 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, 2023, accepted.
2. 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*. A Cryptic Basic Groove formed by Ubiquitin and Histone H3 Mediates the Selective Recognition of H2AK119Ub Nucleosomes by Synovial Sarcoma X Breakpoint 1 Protein. Nature Structural & Molecular Biology, 2023, accepted.
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.
4. 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.
5. 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.

加入SJTU前的工作：
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.（共一和共同通讯）
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.

研究成果以通讯作者/第一作者在Nature, Nat Struct Mol Biol, Nat Chem Biol, Chem, Nat Protoc，Nat Commun, JACS, Angew等权威刊物上累计发表30余篇，获得国家发明专利授权2项。代表性成果如下：
（1）发展了系列泛素修饰的化学合成方法，实现了天然泛素链，磷酸化修饰型泛素链以及多种不同类型泛素修饰蛋白探针的高效体外重构(JACS, 2016ab/Adv Sci, 2018/ CCS Chem, 2019/JACS, 2019/Angew, 2020/Nat Protoc, 2022/Chem, 2023)；
（2）通过上述合成泛素修饰样本，申请人解析了K27链接型泛素修饰的自由及识别状态结构信息(JACS, 2016/Angew 2019)；开发了K29链型构象识别抗体（Nat. Chem. Biol., 2021）；揭示了N端降解机制执行E3酶—Ubr1对底物蛋白的进行K48链型泛素链化修饰的分子机制（Nature, 2021）；
（3）实现了针对泛素修饰识别蛋白机器p97的酶活药物调控评价，并阐明了广谱抗肿瘤药物CuET和广谱抗病毒分子NMS-873选择性抑制p97酶活的分子机制（Nat Struct Mol Biol, 2021/Nat Commun, 2021）。