CHEN Xiaohua
Principal Investigator
Chemical Biology Research Center
Personal Homepage
CONTACT
xhchen@simm.ac.cn
+86(21)-68077993
201203
Biography
Xiao-Hua Chen, Ph.D., Principal Investigator and Professor of Shanghai Institute of Materia Medica, Chinese Academy of Sciences. Dr. Chen received his Ph.D. from Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences under the supervision of Prof. Liu-Zhu Gong in 2008. He joined Prof. Oliver Seitz’ group as Alexander von Humboldt postdoctoral research fellow from 2009-2011 at Humboldt-University Berlin, where his research focused on DNA-directed chemistry and Molecular Diagnostics. In 2012, he joined Prof. Lei Wang’s group at The Salk Institute for Biological Studies and Department of Pharmaceutical Chemistry, University of California, San Francisco as postdoctoral research fellow. Since July 2015, Dr. Chen has worked at Shanghai Institute of Materia Medica, Chinese Academy of Sciences. His research field is about chemical biology and medicinal chemistry, the research interests mainly focus on protein-protein interactions and protein homeostasis, development of new chemistries and small molecules for understanding and modulating signaling processes in human diseases. EDUCATION Sept. 2003-June 2008 Ph.D. in Organic Chemistry, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences Sept. 1999-June 2003 B.Sc. in Chemistry, College of Chemistry and Materials Engineering, Wenzhou University WORK EXPERIENCE July 2015. - present, Principal Investigator, Shanghai Institute of Materia Medica, CAS, Jan. 2012-June 2015, Postdoctoral research fellow, Jack H. Skirball Center for Chemical Biology and Proteomics at the Salk Institute for Biological Studies, and Department of Pharmaceutical Chemistry, University of California, San Francisco. Nov. 2009-Dec. 2011, Alexander von Humboldt postdoctoral research fellow, Department of Organic and Bioorganic Chemistry, Humboldt-University Berlin. Sept. 2008-Oct. 2009, Department of Chemistry, University of Science and Technology of China
Research Directions
1) Develop new chemical biology tools to study protein function in various cellular systems, e.g. developing novel unnatural amino acids via genetic code expansion technology into target proteins, development of novel photoclick chemistry for biomacromolecule interactions, for investigating protein-protein interactions and signaling pathway in native environment, for better understanding of biological processes and pathophysiology. 2) Building platform for discovery of novel degraders (e.g. molecular glue degraders, PROTACs) for targeted protein degradation, based on our developed chemical biology tools, to reprogram the cell’s natural protein degradation system and identify high-quality degraders across a range of disease targets of high unmet clinical need, for drug discovery.
Grants & Research Projects
Achievements
1) Development of light-induced primary amines and o-nitrobenzyl alcohols cyclization (PANAC) as a photoclick reaction via primary amines as direct click handle, to rapid and modular functionalization of diverse small molecules and native biomolecules. The PANAC photoclick chemistry is robust for direct diversification of pharmaceuticals and bioactive small molecules, lysine-specific modification of unprotected peptides and native proteins, spatiotemporal global profiling of protein-protein interactions and protein-DNA interactions, construction of structurally diverse PROTAC degrader libraries and DNA-encoded libraries. The PANAC photoclick chemistry provides a versatile platform for synthetic chemistry, bioconjugation, medicinal chemistry, and chemical biology.
2) Genetic incorporation of novel unnatural amino acids (e.g. o-NBAK, BrC6K，Kbz, 2-F-Kbz, 2, 5-2F-Kbz)) into target proteins for investigating protein-protein interactions and signaling pathway in native environment, for better understanding of biological processes and pathophysiology. These new unnatural amino acids could be used for antibody-drug conjugation and bioactive peptide engineering, enabling the design and development of novel biological diagnostics, imaging tools, and therapeutics.
3) Discovery of potent and selective degraders for targeted protein degradation, such as discovery of highly potent and efficacious CDK9 degrader for targeting transcription regulation, which represents an effective strategy and great potential as a new targeted therapy for TNBC. We also have developed several kinds of molecular glue degraders for targeted protein degradation for cancer therapy.
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Social Titles
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Awards & Honors
2019, Young scientific talents in Shanghai (Shanghai, China)
2016, Shanghai Rising-Star program (The Science and Technology Commission of Shanghai Municipality, China)
2014, Pioneer Fund Postdoctoral Fellowship (Salk Institute)
2009-2011, Alexander von Humboldt Research Fellowship
2010, The Chinese National Excellent Doctoral Dissertation Award
2009, Outstanding Doctoral Dissertation Award of CAS
2009, Top 100 most cited chinese papers published in international journals (Institute of Scientific and Technical Information of China)
2008, The Special Award of the Presidential Fellowship of CAS
2007, Roche Creative Chemistry Award (Roche R&D Center, China)
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Pubilcations
Full Publication List
Selected Publications
1. An-Di Guo,+ Ke-Nian Yan,+ Hao Hu,+ Linhui Zhai, Teng-fei Hu, Haixia Su, Yijia Chi, Jinyin Zha, Yechun Xu, Dongxin Zhao, Xiaojie Lu, Yong-Jiang Xu, Jian Zhang, Minjia Tan,* Xiao-Hua Chen*. Spatiotemporal and global profiling of DNA-protein interactions enables discovery of low-affinity transcription factors. Nat. Chem., 2023, 15, 803-814; DOI: 10.1038/s41557-023-01196-z.（+ contributed equally）
2. Yali Xu+, Wensi Zhao+, Hui-Jun Nie+, Jiamin Wang+, Jingjing Fu, Hao Hu, Zihao Liu, Shengna Tao, Mingya Zhang, Yubo Zhou, Jia Li*, Minjia Tan*, Xiao-Hua Chen*. Cross-Linking Profiling of Molecular Glue Degrader-Induced E3 Ligase Interactome to Expand Target Space. Angew. Chem. Int. Ed. 2025, 64, e202505053.（+ contributed equally）
3. Hao Hu,+ Wei Hu,+ An-Di Guo,+ Linhui Zhai,+ Song Ma, Hui-Jun Nie, Bin-Shan Zhou, Tianxian Liu, Xinglong Jia, Xing Liu, Xuebiao Yao, Minjia Tan* Xiao-Hua Chen*. Spatiotemporal and direct capturing global substrates of lysine-modifying enzymes in living cells. Nat. Commun., 2024, 15, 1465. DOI :10.1038/s41467-024-45765-3 (+ contributed equally ).
4. Ke-Nian Yan,+ Yong-Qiang Nie,+ Jia-Yu Wang,+ Guang-Liang Yin, Qia Liu, Hao Hu, Xiaoxia Sun* and Xiao-Hua Chen*. Accelerating PROTACs Discovery through a Direct-to-Biology Platform Enabled by Modular Photoclick Chemistry. Advanced Science, 2024, 11, 2400594. DOI: 10.1002/advs.202400594. (+, contributed equally )
5. An-Di Guo,+ Dan Wei,+ Hui-Jun Nie,+ Hao Hu, Chengyuan Peng, Shao-Tong Li, Ke-Nian Yan, Bin-Shan Zhou, Lei Feng, Chao Fang, Minjia Tan, Ruimin Huang, Xiao-Hua Chen*. Light-induced primary amines and o-nitrobenzyl alcohols cyclization as a versatile photoclick reaction for modular conjugation; Nat. Commun., 2020, 11, 5472; (+, contributed equally ).
6. Wei Hu, Yi Yuan, Cai-Hu Wang, Hong-Tao Tian, An-Di Guo, Hui-Jun Nie, Hao Hu, Minjia Tan, Zhuo Tang,* Xiao-Hua Chen*. Genetically Encoded Residue-Selective Photo-Crosslinker to Capture Protein-Protein Interactions in Living Cells; Chem., 2019, 5, 2955-2968.
7. Hui-Jun Nie+, Hao Hu+, Xinming Qi+, Yin-Jue Zhou, Lu Liu, Xiao-Hua Chen*. General Platform for Efficient and Modular Assembly of GalNAc–siRNA Conjugates via Primary Amines and o-Nitrobenzyl Alcohol Cyclization Photoclick Chemistry Enabling Rapid Access to Therapeutic Oligonucleotides. JACS Au 2025, 5, 3, 1402–1412. (+, contributed equally ).
8. Wen-Jing Wang+, Lixin Gao+, Simei Wang+, Wensi Huang+, Xin-Yu Meng, Hao Hu, Ziqiang Chen, Jingya Sun, Yali Yuan, Yubo Zhou, Xingxing Diao*, Ruimin Huang*, Jia Li*, Xiao-Hua Chen*. Discovery of Orally Bioavailable and Potent CDK9 Inhibitors for Targeting Transcription Regulation in Triple-Negative Breast Cancer. J. Med. Chem., 2024, 67, 10035–10056. (+, contributed equally ).
9. Dan Wei,+ Hanlin Wang,+ Qinghe Zeng,+ Wenjing Wang, Bingbing Hao, Xule Feng, Peipei Wang, Ning Song, Weijuan Kan, Guifang Huang, Xiaoyu Zhou, Minjia Tan, Yubo Zhou, Ruimin Huang,* Jia Li,* Xiao-Hua Chen*. Discovery of Potent and Selective CDK9 Degraders for Targeting Transcription Regulation in Triple-Negative Breast Cancer; J. Med. Chem., 2021, 64, 14822-14847 ( +, contributed equally )
10. Yan Xu, Dingqiang Fu, Yi Yuan, Yan Peng, Juan Dong, Feng Du, Xin Huang, Guangxun Li, Xiaohua Chen,* Qiwei Wang,* and Zhuo Tang*; A heterobifunctional molecule recruits cereblon to an RNA scaffold and activates its PROTAC function，Cell Reports Physical Science, 2022, 3, 101064.
11. Hui-Jun Nie+, Ying-Jie Fu+, Shang Long, Jia-Yu Wang, Wensi Zhao, Linhui Zhai, Yin-Long Yang, Minjia Tan, Hao Hu*, Xiao-Hua Chen*. Chemoproteomics reveals proteome-wide covalent and non-covalent targets of withaferin A. Acta Pharmacologica Sinica, 2025, DOI: 10.1038/s41401-024-01468-5 ( +, contributed equally )
12. Zhi-Feng, Zou,+ Lei, Yang,+ Hui-Jun, Nie,+ Jing, Gao,* Shu-Min, Lei, Yi, Lai, Fan, Zhang, Ernst, Wagner, Hai-Jun, Yu,* Xiao-Hua, Chen,* Zhi-Ai, Xu*. Tumor-targeted PROTAC prodrug nanoplatform enables precise protein degradation and combination cancer therapy. Acta Pharmacologica Sinica, 2024, DOI: 10.1038/s41401-024-01266-z. (+, contributed equally )
13. Hui-Jun Nie+, Ben-Fu Li+, Jingya Sun+, Yali Yuan+, Zhi-Gao Zhang, Hao Hu, Wen-Jing Wang, Ziqiang Chen, Simei Wang, Wensi Huang, Xingxing Diao, Jinghua Yu*, Ruimin Huang*, Xiao-Hua Chen*. Discovery of a Potent, selective and orally bioavailable CDK9 degrader for targeting transcription regulation in Triple-Negative breast cancer. Bioorganic Chemistry, 2024, 153, 107876. (+, contributed equally).
14. Yanrui Suo, Kaige Li, Xing Ling, Kenian Yan, Weiwei Lu, Jinfeng Yue, Xiao-Hua Chen*, Zhiqiang Duan*, Xiaojie Lu*. Discovery Small-Molecule p300 Inhibitors Derived from a Newly Developed Indazolone-Focused DNA-Encoded Library. Bioconjugate Chem. 2024, 35, 1251–1257.
15. Hongtao Tian, jiale yang, An-Di Guo, Yu Ran, Yun-Zhi Yang, Bing Yang,Ruimin Huang, Haiming Liu*, Xiao-Hua Chen*. Genetically Encoded Benzoyllysines Serve as Versatile Probe for Interrogating Histone Benzoylations and Interactions in Living Cells; ACS Chem. Biol., 2021,16, 2560-2569.
16. An-Di Guo, Ke-Huan Wu, Xiao-Hua Chen*. Light-induced efficient and residue-selective bioconjugation of native proteins via indazolone formation; RSC Advances, 2021, 11, 2235.
17. Hui-Jun Nie, An-Di Guo, Hai-Xia Lin, Xiao-Hua Chen*. Rapid and halide compatible synthesis of 2-Nsubstituted indazolone derivatives via photochemical cyclization in aqueous media, RSC Adv., 2019, 9, 13249-13253.
18. Nan Li,* Honglian Feng, Qian Gong, Chunxiao Wu, Hao Zhou, Zhiyan Huang, Jun Yang, Xiao-Hua Chen,* Na Zhao.* BINOL-based chiral aggregation-induced emission luminogens and t.heir application in detecting copper(II) ions in aqueous media. J. Mater. Chem.C, 2015, 3, 11458-11463.
19. Xiao-Hua Chen, Zheng Xiang, Ying S. Hu, Vanessa K. Lacey, Hu Cang, and Lei Wang*. Genetically Encoding an Electrophilic Amino Acid for Protein Stapling and Covalent Binding to Native Receptors. ACS Chem. Biol., 2014, 9, 1956-1961.
20. Xiao-Hua Chen, Alexander Roloff, Oliver Seitz*. Consecutive Signal Amplification for DNA Detection Based on De Novo Fluorophore Synthesis and Host-Guest Chemistry. Angew. Chem. Int. Ed., 2012, 51, 4479-4483.
21. Xiao-Hua Chen, Jie Yu and Liu-Zhu Gong*. The Role of Double Hydrogen Bonds in Asymmetric Direct Aldol Reactions Catalyzed by Amino Amide Derivatives. Chem. Commun., 2010, 46, 6437-6448.
22. Xiao-Hua Chen, Qiang Wei, Shi-Wei Luo, Han Xiao, and Liu-Zhu Gong*. Organocatalytic Synthesis of Spiro[pyrrolidin-3,3′-oxindoles] with High Enantiopurity and Structural Diversity. J. Am. Chem. Soc.; 2009, 131, 13819-13825
23. Xiao-Hua Chen, Wen-Quan Zhang, and Liu-Zhu Gong*. Asymmetric Organocatalytic Three-Component 1,3-Dipolar Cycloaddition: Control of Stereochemistry via a Chiral Bronsted Acid Activated Dipole. J. Am. Chem. Soc.; 2008, 130, 5652-5653.
24. Xiao-Hua Chen, Xiao-Ying Xu, Hua Liu, Lin-Feng Cun, and Liu-Zhu Gong*. Highly Enantioselective Organocatalytic Biginelli Reaction. J. Am. Chem. Soc.; 2006, 128, 14802-14803.
25. Xiao-Hua Chen, Shi-Wei Luo, Zhuo Tang, Lin-Feng Cun, Ai-Qiao Mi, Yao-Zhong Jiang, and Liu-Zhu Gong*. Organocatalyzed Highly Enantioselective Direct Aldol Reactions of Aldehydes with Hydroxyacetone and Fluoroacetone in Aqueous Media. The Use of Water to Control the Regioselectivity. Chem. Eur. J.; 2007. 13. 689-701.
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