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The Skaggs Institute for Chemical Biology
Faculty, Graduate Program

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Academia Sinica, Taipei, Taiwan

Research Focus

Watch Welch Award in Chemistry video: https://welch1.org/awards/welch-award-in-chemistry

Research in the Wong lab encompasses a broad spectrum of bioorganic and synthetic chemistry. Current interest is centered on the development of discovery tools for understanding the role of biological glycosylation in cancer progression, bacterial and viral infection, neurodegenerative disorder and immune response. Programmable one-pot synthesis as well as chemo-enzymatic synthesis of oligosaccharides and homogeneous glycoproteins, and design of glycan microarrays and glycosylation probes are among the tools being developed for the study of cell-surface glycoconjugates. The ultimate goal of our research is to leverage our understanding of biologyical glycosylation for therapeutic development, including the development of universal vaccines against viral infection and cancer, homogeneous antibodies with optimized effector functions, and inhibitors of key enzymes involved in the biosynthesis of glycan targets.

Education

Ph.D., Organic Chemistry, MIT (with G. M. Whitesides), 1982
M.S., Biochemical Sciences, National Taiwan University, 1977
B.S., Biochemical Sciences, National Taiwan University, 1970

Professional Experience

2019-Present: Scripps Family Chair Professor, Department of Chemistry, The Scripps Research Institute.
2016-Present: Distinguished Research Fellow, Genomics Research Center, Academia Sinica, Taiwan.
2006-2019: Professor of Chemistry, The Scripps Research Institute.
2003-2006: Director, Genomics Research Center, Academia Sinica, Taiwan.
2006-2016: President, Academia Sinica
1996-2006: Member, The Skaggs Institute for Chemical Biology, Scripps Research
1989-2006: Ernest W. Hahn Professor of Chemistry, Chemistry, Scripps Research
1989-2006: Faculty Member, Skaggs Graduate School of Chemical and Biological Sciences, Scripps Research
1991-1999: Head, Frontier Research Program on Glycotechnology, RIKEN: Institute of Physical and Chemical Research
1987-1989: Professor of Chemistry, Texas A&M University
1987-1989: Professor, Department of Biochemistry and Biophysics and the Institute of Biosciences and Technology, Texas A&M University
1986-1987: Associate Professor of Chemistry, Texas A&M University
1983-1986: Assistant Professor of Chemistry, Texas A&M University
1982-1983: Postdoctoral Fellow with G.M. Whitesides, Harvard University

Awards & Professional Activities

Selected References

Koeller, K., Wong, C.-H., "Enzymes for chemical synthesis," Nature, 2001, 409, 232-240.

Sears, P., Wong, C.-H., "Toward automated synthesis of oligosaccharides and glycoproteins," Science, 2001, 291, 2344-2350.

Shie, J.-J., Liu, Y.-C., Lee, Y.-M., Lim, C., Fang, J.-M., Wong, C.-H., “An azido-BODIPY probe for glycosylation: initiation of strong fluorescence upon triazole formation”, J. Am. Chem. Soc., 2014, 136, 9953-9961.

Lin, C.-W. et al., “A common glycan structure on immunoglobulin G for enhancement of effector functions”, Proc. Nat. Acad. Sci. U.S.A., 2015, 112, 10611-10616.

Danishefsky, S.J., Shue, Y.-K., Chang, M.N., Wong, C.-H., "Development of Globo-H Cancer Vaccine," Acc. Chem. Res., 2015, 48, 643-652.

Shivatare, S.S. et al., "Modular Synthesis of N-glycans and Arrays for the Hetero-ligand Binding Analysis of Antibodies," Nature Chem., 2016, 8, 338-346.

Krasnova, L.  and Wong, C.-H., “Understanding the chemistry and biology of glycosylation with glycan synthesis”, Annual Review of Biochemistry, 2016, 85, 599-630.

Kizuka, Y. et al., “High sensitivity and low toxicity fucose probe for glycan imaging and biomarker discovery”, Cell Chem. Biol., 2016, 23, 782-792.

Huang, Y.-W. et al., “Residues comprising the enhanced aromatic sequon influence protein N-glycosylation efficiency”, J. Am. Chem. Soc., 2017, 139, 12947-12955.

Tseng, T.-H. et al., “Substrate preference and interplay of fucosyltransferase 8 and N-acetylglucosaminyltransferases”, J. Am. Chem. Soc., 2017, 139, 9431-9434.

Liu, C.-P. Shivatare, V. S., Wu, C.-Y., Wong, C.-H., “Glycoengineering of antibody (Herceptin) through yeast expression and in vitro enzymatic glycosylation”, Proc. Nat. Acad. Sci. U.S.A., 2018, 115, 720-725.

Wu, W.-S., Cheng, W.-C., Cheng, T.-R., Wong, C.-H., “Affinity-based screen for inhibitors of bacterial transglycosylase”,  J. Am. Chem. Soc., 2018, 140, 2752-2755.

Shivatare, V. S. et al., “Unprecedented role of hybrid N-glycans as ligands for HIV-1 broadly neutralizing antibodies”, J. Am. Chem. Soc., 2018, 140, 5202-5210.

Lo, P.-W., Shie, J.-J., Chen, C.-H., Wu, C.-Y., Hsu, T.-L., Wong, C.-H., “O-GlcNAcylation regulates the stability and enzymatic activity of the histone methyltransferase EZH2”, Proc. Nat. Acad. Sci. U.S.A., 2018, 115, 7302-7307.

Dey, S. and Wong, C.-H., “Programmable one-pot synthesis of heparin pentasaccharides enabling access to regiodefined sulfate derivatives”, Chem. Sci., 2018, 9, 6685-6691.

Cheng, C.-W. et al., “Hierarchical and programmable one-pot synthesis of oligosaccharides”, Nature Commun., 2018, 9, 5202.

Krasnova, L. and Wong, C.-H., “Oligosaccharide synthesis and translational innovation”, J. Am. Chem. Soc., 2019, 141, 3735-54.

Chuang, P.-K. et al., “Functional study and signaling pathway of globo-series glycosphingolipids and β1,3-galactosyltransferase V (β3GalT5) in breast cancer”, Proc. Nat. Acad. Sci. U.S.A., 2019, 116, 3518-23.

Tseng, Y.-C. et al., “Egg-based influenza split virus vaccine with monoglycosylation induces cross-strain protection against influenza virus infections”, Proc. Nat. Acad. Sci. U.S.A., 2019, 116, 4200-05.

Lo, H.-J. et al., “Synthesis of sialidase-resistant oligosaccharide and antibody glycoform containing α2,6-linked 3F^ax-Neu5Ac”, J. Am. Chem. Soc., 2019, 141, 6484-6488.

Liao, H.-Y. et al. "Chimeric hemagglutinin vaccine elicits broadly protective CD4 and CD8 T cell responses against multiple influenza strains and subtypes" Proc. Natl. Acad. Sci. U.S.A. 2020, 117, 17757-63.

Lin, C.-W. et al. “Homogeneous antibody and CAR-T cell targeting glycan on pancreatic cancer”, Proc. Natl. Acad. Sci. U.S.A. 2021, 118, 50 e2114774118.

Chen, C.-Y. et al. “Synthesis of Azido-Globo H Analogs for Immunogenicity Evaluation”, ACS Cent. Sci. 2022, 8, 77-85.

Wu, C.-Y. et al. “Glycosite-deleted mRNA of SARS-CoV-2 Spike Protein as Broad-Spectrum Vaccine”, Proc. Natl. Acad. Sci. U.S.A. 2022, 119 (9) e2119995119.

Huang, H.-Y. et al. “Vaccination with SARS-CoV-2 spike protein lacking glycan shields elicits enhanced protective responses in animal models", Sci. Transl. Med. 2022. DOI: 10.1126scitranslmed.abm0899.

Shivatare, S.S. and C.-H. Wong.  “Glycoconjugates: synthesis, functional studies and therapeutic developments,” Chem. Rev. 2022, Invited contribution.

Tseng, Y.-Y. et al. “Tackling multidrug-resistant Helicobacter Pylori with moenomycin A in combination with clarithromycin or metronidazole”, Frontiers in Chemistry. 2022, Invited contribution.

Links

Chi-Huey Wong - Welch Award in Chemistry - 2021

Chi-Huey Wong - Wolf Prize Laureate in Chemistry – 2014

The Skaggs Institute for Chemical Biology

Molecules Caught in the Act-- Scientists at TSRI Solve Elusive Enzyme Mechanism

The Skaggs Institute Scientific Report

Antivirals, Anti-Cancers, and Antibiotics in One Pot