师资名录

艾华松

长聘教轨副教授

 

邮箱:huasongai@sjtu.edu.cn; ahs17@tsinghua.org.cn

艾华松 博士,长聘教轨副教授、课题组长(PI)、博士生导师。2017年7月年本科毕业于清华大学药学院;2022年6月博士毕业于清华大学化学系,导师为刘磊教授;2022年7月至2024年7月年在清华大学从事博士后研究;2024年8月加入上海交通大学药学院。

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28篇论文,以第一(含共同)作者或通讯作者在Nat. Chem. Biol.(3篇), Nat. Struct. Mol. Biol.(2篇), Mol. Cell(1篇), Chem(1篇), J. Am. Chem. Soc.(1篇), 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.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)等项目。
地址:办公室/实验室,药学院六号楼107/108室
课题组主要聚焦靶向翻译后修饰串扰(targeting PTM crosstalk)的化学生物学合成方法与探针工具的开发,并进行生化、结构功能机制阐释与化学调控研究。

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;通过生化酶学、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,位点特异性擦除机制,解析白血病、滑膜肉瘤等疾病相关的调控机制等。共发表论文28篇,其中以第一(含共同)作者或通讯作者在Nat. Chem. Biol., Nat. Struct. Mol. Biol., Mol. Cell, Chem, J. Am. Chem. Soc., ACS Cent. Sci., Chem. Sci. 等期刊发表高水平论文13篇。
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/K15 Mono- and Adjacent Dual- Ubiquitination by RNF168. Nature Chemical Biology, 2024, In Press. (bioRxiv, 2024, https://doi.org/10.1101/2024.01.02.573964)
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, doi: 10.1038/s41594-024-01342-2.
3. 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.
4. 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.
5. 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.
6. Huasong Ai, Lei Liu*. Paralog-specific recognition. Nature Chemical Biology, 2023, 5, 542-543.
7. Huasong Ai, Man Pan, Lei Liu*. Chemical synthesis of human proteoforms. ACS Central Science, 2024, 10, 1442-1459.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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. (bioRxiv, 2024, https://doi.org/10.1101/2024.07.22.604500)
13. 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.
14. 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,通过蛋白化学合成技术构建覆盖全泛素化组蛋白(核小体)的样品文库(H1K82Ub, H2AK13/15Ub,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、修饰串扰机制研究等,贡献蛋白型态精度的生命科学研究。

2. 为克服酶与底物弱且瞬时的相互作用特征,提出了构建酶学中间体模拟物的化学捕获思路,并融合分裂内含肽(split-intein)的剪接技术,基于活性的交联探针策略,发展了以“CAET”化学为核心的稳定染色质泛素化中间体的化学生物学方法系统。深入研究底物位点特异性泛素化、去泛素化等酶学过程的活性、选择性、催化反应的机制,为实现底物特异性的酶学靶向干预奠定基础。

3. 靶向翻译后修饰串扰(PTM crosstalk),发展了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。

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