Shanghai Institute of Material Medical Chinese Academy of Sciences

Biography

Xiao-Hua Chen, Ph.D., Principal Investigator 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 interests mainly focus on genetic incorporation of unnatural amino acids into proteins for investigating protein-protein interactions, development of new chemistries for protein labeling and modification, peptide engineering and discovery of bioactive small molecules for drug development.

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) Genetic incorporation of novel unnatural amino acids into target proteins for investigating protein-protein interactions and signaling pathway in native environment, for better understanding of biological processes and pathophysiology.

2) Design of functional probes for chemical biology research, such as drug discovery, disease diagnosis and cell imaging.

3) Development of novel degraders for targeted protein degradation for cancer research.

4) Asymmetric catalytic synthesis, diversity-oriented synthesis of privileged structure with biological activities for medicinal chemistry

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 is robust for direct diversification of pharmaceuticals and biorelevant molecules, lysine-specific modifications of unprotected peptides and native proteins in vitro, temporal profiling of endogenous kinases and organelle-targeted labeling in living systems. The PANAC photoclick provides a versatile platform for organic synthesis, bioconjugation, medicinal chemistry, chemical biology and materials science.

2) Genetic incorporation of novel unnatural amino acids (e.g. o-NBAK, BrC6K) 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 other novel degraders for targeted protein degradation in cancer cells.

4) Asymmetric catalytic synthesis, diversity-oriented synthesis of privileged structure with biological activities for medicinal chemistry

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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. 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, https://doi.org/10.1021/acs.jmedchem.1c01350; ( +, contributed equally ).

2. 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 Chemical Biology, 2021, in press.

3. 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.

4. 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 ).

5. 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.

6. 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.

7. 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.

8. 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 Chemical Biology, 2014, 9, 1956-1961.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. Liu-Zhu Gong,* Xiao-Hua Chen, and Xiao-Ying Xu. Asymmetric Organocatalytic Biginelli Reactions: a New Approach to Quickly Access Optically Active 3, 4-Dihydropyrimidin-2-(1H)-ones. Chem. Eur. J .; 2007, 13. 8920-8926.

16. Long He, Xiao-Hua Chen, De-Nan Wang, Shi-Wei Luo*, Wen-Quan Zhang, Jie Yu, Lei Ren, and Liu-Zhu Gong*. Binaphthol-derived Bisphosphoric Acids Serve as Efficient Organocatalysts for Highly Enantioselective 1, 3-Dipolar Cycloaddition of Azomethine Ylides to Electron-Deficient Olefins. J. Am. Chem. Soc.; 2011, 133, 13504-13518.

17. Nan Li, Xiao-Hua Chen, Shi-Ming Zhou, Shi-Wei Luo, Jin Song, Lei Ren, and Liu-Zhu Gong*. Asymmetric Amplification in Phosphoric Acid Catalyzed Reactions. Angew. Chem. Int. Ed., 2010, 49, 6378-6381.

18. Chao Wang, Xiao-Hua Chen, Shi-Ming Zhou and Liu-Zhu Gong*. Asymmetric Organocatalytic Formal Double-arylation of Azomethines for the Synthesis of Highly Enantiomerically Enriched Isoindolinesw. Chem. Commun., 2010, 46, 1275-1277.

19. Nan Li, Xiao-Hua Chen, Jin Song, Shi-Wei Luo, Wu Fan, and Liu-Zhu Gong*. Highly Enantioselective Organocatalytic Biginelli and Biginelli-Like Condensations: Reversal of the Stereochemistry by Tuning the 3, 3′-Disubstituents of Phosphoric Acids. J. Am. Chem. Soc.; 2009, 131, 15301-15310.

20. Zhi-Yong Han, Han Xiao, Xiao-Hua Chen, and Liu-Zhu Gong*. Consecutive Intramolecular Hydroamination/Asymmetric Transfer Hydrogenation under Relay Catalysis of an Achiral Gold Complex/Chiral Br？nsted Acid Binary System. J. Am. Chem. Soc.; 2009, 131, 9182-9183.

21. Wei-Jun Liu, Xiao-Hua Chen, and Liu-Zhu Gong*. Direct Assembly of Aldehydes, Amino Esters, and Anilines into Chiral Imidazolidines via Bronsted Acid Catalyzed Asymmetric 1, 3-Dipolar Cycloadditions. Org. Lett.; 2008, 10, 5357-5360.

22. Zhuo Tang, Zhi-Hua Yang, Xiao-Hua Chen, Lin-Feng Cun, Ai-Qiao Mi, Yao-Zhong Jiang, Liu-Zhu Gong*. A Highly Efficient Organocatalyst for Direct Aldol Reactions of Aldehydes with Ketones. J. Am. Chem. Soc.; 2005, 127, 9285-9289.

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