教育经历
2017.7-2022.6 清华大学，博士， 化学系 有机化学专业（导师：刘磊教授）
2013.9-2017.6 清华大学，本科， yd12300云顶线路 药学专业

工作经历
2024.8-至今 长聘教轨副教授，课题组长（PI）、博士生导师，yd12300云顶线路，上海，中国
2022.7-2024.7 助理研究员、博士后，清华大学化学系（刘磊），北京，中国
2019.1-2019.7 访问学者，芝加哥大学（Minglei Zhao赵明磊），芝加哥，美国

曾入选清华大学高层次青年人才项目“水木学者”计划，美国芝加哥大学生化与分子生物学系访问学者，上海交通大学转化医学国家重大科技基础设施（上海）访问学者，中国化学会会员，获评清华大学化学系优秀博士后卓越奖（三次）、创新奖，清华大学优秀博士毕业论文等奖项。共发表31篇论文，以第一作者或通讯作者（含共同）在Nat. Chem. Biol.（3篇）, Nat. Struct. Mol. Biol.（2篇）, Mol. Cell（1篇）, Chem（1篇）, J. Am. Chem. Soc.（1篇）, Angew. Chem. Int. Ed.（1篇）, ACS Cent. Sci. （1篇）, Chem. Sci.（1篇）等国际权威期刊发表高水平论文13篇，曾担任Nat. Chem. Biol.，Nat. Struct. Mol. Biol., J. Am. Chem. Soc.等期刊审稿人，主持中国博士后科学基金特别资助（站前）、面上资助（一等）、上海市药物靶标发现及递送前沿科学研究基地面上项目等。

地址：上海市闵行区东川路800号yd12300云顶线路6号楼107/108室

1. 翻译后修饰的化学生物学方法与探针工具开发，功能机制、与化学调控研究；

2. 染色质翻译后修饰相关靶点鉴定与药物发现；

围绕上述研究方向，发展了多种以蛋白质合成化学为基础的翻译后修饰蛋白的合成新策略、新探针；通过生物化学、化学生物学、结构生物学等技术解码研究“组蛋白泛素密码”，包括定点生成机制、功能传递的识别机制、与其它修饰串扰机制，位点特异性擦除机，解析MLL白血病、滑膜肉瘤、唐氏综合症等疾病相关的重要蛋白质机器调控过程。

欢迎对本课题组研究方向感兴趣的本科生、研究生加入，另诚聘博士后、研究助理多名，欢迎联系！

First, co-first and/or co-corresponding authored papers:

After SJTU:
1. Yunxiang Du#, Maoshen Sun#, ZhengQing Li#, Xiangwei Wu, Qian Qu*, Huasong Ai* (共通讯), Lei Liu*. Mechanistic Insights into the Stimulation of the Histone H3K9 Methyltransferase Clr4 by Proximal H3K14 Ubiquitination. bioRxiv, 2024, doi.org/10.1101/2024.09.28.615623.

2. Qiang Shi#, Zhiheng Deng#, Liying Zhang#, Zebin Tong, Jia-Bin Li, Guo-Chao Chu*, Huasong Ai* (共通讯), and Lei Liu*. Promotion of RNF168-Mediated Nucleosomal H2A Ubiquitylation by Structurally-defined K63-Polyubiquitylated Linker Histone H1. Angew. Chem. Int. Ed., 2024, e202413651

3. 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/K15 Mono- and Adjacent Dual- Ubiquitination by RNF168. Nature Chemical Biology, 2024, doi.org/10.1038/s41589-024-01750-x.

Before SJTU:
4. 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: 10.1038/s41594-024-01342-2.

5. Huasong Ai#, Maoshen Sun#, Aijun Liu#, Zixian Sun#, Tingting Liu#, Lin Cao, Lujun Liang, Qian Qu, Zichen Li, Zhiheng Deng, Zebin Tong, Guochao Chu, Xiaolin Tian, Haiteng Deng, Suwen Zhao, Jiabin Li, Zhiyong Lou, Lei Liu. H2B Lys34 ubiquitination induces nucleosome distortion to stimulate Dot1L activity. Nature Chemical Biology, 2022, 18, 972-980.

6. Huasong Ai#, Guochoa Chu#, Qingyue Gong#, Zhiheng Deng, Zebin Tong, Xin Liu, Fan Yan, Jiabin Li*, Changlin Titan*, Lei Liu*. Chemical synthesis of ubiquitinated and/or phosphorylated H2AX reveals combinational outcome of histone modifications in 53BP1 binding. Journal of the American Chemical Society, 2022, 144, 18329-18337.

7. Huasong Ai#, Zebin Tong#, Zhiheng Deng, Jiakun Tian, Liying Zhang, Maoshen Sun, Yunxiang Du, Ziyu Xu, Qiang Shi, Lujun Liang, Qingyun Zheng, Jiabin Li, Man Pan*, Lei Liu*. Synthetic E2-Ub-nucleosome conjugates for studying nucleosome ubiquitination. Chem, 2023, 9, 1221-1240.

8. Huasong Ai, Lei Liu*. Paralog-specific recognition. Nature Chemical Biology, 2023, 5, 542-543.

9. Huasong Ai, Man Pan, Lei Liu*. Chemical synthesis of human proteoforms. ACS Central Science, 2024, 10, 1442-1459.

10. Huasong Ai, Yu Guo, Demeng Sun, Sanling Liu, Yunkun Qi, Jing Guo, Qian Qu, Qingyue Gong, Suwen Zhao,* Jiabin Li,* and Lei Liu*. Examination of the Deubiquitylation Site Selectivity of USP51 by Using Chemically Synthesized Ubiquitylated Histones. ChemBioChem, 2019, 20, 221-229.

11. Huasong Ai, Shuai Peng, Jia-Bin Li. Chemical methods for studying the crosstalk between histone H2B ubiquitylation and H3 methylation. Journal of Peptide Science, 2021, e3381.

12. Zebin Tong#, Huasong Ai#, *(共一/共通讯), 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.

13. Zhiheng Deng#, Huasong Ai# (共一), Maoshen Sun#, Zebin Tong#, Yunxiang Du#, Qian Qu, Liying Zhang, Ziyu Xu, Shixian Tao, Qiang Shi, Jia-Bin Li, Man Pan, and Lei Liu*. Mechanistic insights into nucleosomal H2B monoubiquitylation mediated by yeast Bre1-Rad6 and its human homolog RNF20/RNF40-hRAD6A. Molecular Cell, 2023, 83, 3080-3094.E14.

14. Zichen Li#, Zebin Tong#, Qingyue Gong#, Huasong Ai* (共通讯), Shuai Peng, Cong Chen, Guo-Chao Chu, Jia-Bin Li*. The expedient, CAET-assisted synthesis of dual-monoubiquitinated histone H3 enables evaluation of its interaction with DNMT1. Chemical Science, 2023,14, 5681-5688.

15. Junxiong Mao#, Huasong Ai# (共一), Xiangwei Wu#, Qingyun Zheng*, Hongyi Cai, Lujun Liang, Zebin Tong, Man Pan*, Lei Liu*. Structural Visualization of HECT-E3 Ufd4 accepting and transferring Ubiquitin to Form K29K48-branched Polyubiquitination on N-degron. bioRxiv, 2023, doi:10.1101/2023.05.23.542033.

16. Yunkun Qi#, Huasong Ai# (共一), Yiming Li, Binghui Yan. Total Chemical Synthesis of Modified Histones. Frontiers in Chemistry, 2018, 6, 19.

1. 突破生物重组表达的限制，合成构建覆盖全泛素化组蛋白/核小体的样品库平台（H1K82Ub，H2AK13Ub, H2AK15Ub，H2AK119Ub，H2AK125/127/129Ub，H2BK34Ub，H2BK120Ub，H3K14Ub，H3K18/23Ub，H3K122Ub）。用于体外精准活性重构、定量活性关系探索、效应蛋白识别研究，贡献蛋白型态精度的生命科学研究。

2. 克服酶与底物弱且瞬时的互作特征，提出了构建染色质泛素化酶学中间体模拟物的交联思路，融合基于活性的交联探针、分裂内含肽（split-intein）的剪接技术等，建立以“CAET”化学为核心的生物大分子定点交联的方法系统。深入研究染色质泛素化、去泛素化过程的活性、选择性催化机制，为实现底物特异性的酶学靶向干预奠定结构基础。

3. 靶向翻译后修饰串扰（targeting PTM crosstalk），运用化学生物学合成方法与探针工具，聚焦重大疾病相关的蛋白质机器进行结构功能机制阐释与化学调控研究，揭示滑膜肉瘤等疾病的新型可药靶点，助力生物医药发展。