Professor Chi-Huey WONG's Laboratory

Group Focus

Research in Professor Wong's lab. encompasses a broad spectrum of bioorganic and synthetic chemistry, aiming to understand carbohydrates in biology and develop new therapeutic strategies and devices. Development of novel molecular structures to investigate how they interact with cells and learn more about the mechanism and function of those molecules and disease progression. Programmable one-pot reactions are being developed for the synthesis of complex oligosaccharides and glycoarrays and complement new chemo-enzymatic strategies for the synthesis of glycoproteins, vaccines and other biologically active molecules to tackle major problems in biology and medicine, especially those associated with cancer and infectious diseases.

About Professor Chi-Huey WONG



Postdoctoral Fellow, Department of Chemistry, Harvard University
Ph.D. in Chemistry, Department of Chemistry, MIT
M.S. in Biochemical Sciences, National Taiwan University
B.S. in Biochemical Sciences, National Taiwan University

Academic Appointments

Scripps Family Chair Professor of Chemistry, The Scripps Research Institute, USA; Joint appointment as Distinguished Research Fellow, Genomics Research Center, Academia Sinica, Taiwan
Distinguished Research Fellow, Genomics Research Center, Academia Sinica, Taiwan; Joint appointment as Professor of Chemistry, The Scripps Research Institute, USA
President, Academia Sinica, Taipei, Taiwan
Director and Distinguished Research Fellow, Genomics Research Center, Academia Sinica, Taipei, Taiwan
Member, the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA
Head, Frontier Research Program on Glycotechnology, RIKEN, Japan
Professor and Ernest W. Hahn Chair in Chemistry, The Scripps Research Institute, La Jolla, California, USA
Assistant Professor (1983–1986), Associate Professor (1986–1987), and Professor (1987–1989) of Chemistry, Texas A&M University, USA


Elected Member of ITRI (Industrial Technology Research Institute) Laureates
The Royal Society of Chemistry Robert Robinson Award, UK
The Wolf Prize in Chemistry
Elected Fellow of the U.S. National Academy of Inventors
The Nikkei Asia Prize for Science, Technology and Innovation, Japan
The American Chemical Society Arthur C. Cope Award
Elected Associate Member of the European Molecular Biology Organization (EMBO)
National Science Council Science Professional Gold Medal, Taiwan
The F. A. Cotton Medal for Excellence in Chemical Research, USA
Elected Member of the World Academy of Sciences
Humboldt Research Award for Senior Scientists, Germany
The Georges Smets Chair Award for Organic or Polymer Chemistry, Louvain-la-Neuve, Belgium
Elected Fellow of the American Association for the Advancement of Science
The American Chemical Society Award for Creative Work in Synthetic Organic Chemistry
Elected Member of the US National Academy of Sciences
NIH Merit Award, USA
The Presidential Green Chemistry Challenge Award, USA
The International Enzyme Engineering Award
The American Chemical Society San Diego Section Outstanding Scientist Award
The American Chemical Society Claude S. Hudson Award in Carbohydrate Chemistry
The American Chemical Society Harrison Howe Award in Chemistry
The Taiwanese American Foundation Prize in Science and Engineering
Elected Member of The American Academy of Arts and Sciences
The ACS Division of Carbohydrate Chemistry Melville L. Wolfrom Award
Elected Member of Academia Sinica, Taiwan
The Roy Whistler Award of International Carbohydrate Organization
American Chemical Society Arthur C. Cope Scholar Award
Presidential Young Investigator Award in Chemistry, USA
Searle Scholar Award in Biomedical Sciences, USA

Research Interests

Click [Google Scholar] to see our all publications.

Glycan Synthesis

The access to the structure-defined glycan samples in a pure (homogeneous) form is instrumental to the study of glycosylation and the development of therapeutic agents targeting the malfunctioning (e.g., cancerous) glycosylation processes, as well as glycosylation patterns associated with bacterial and viral infections. Currently, chemical and enzymatic syntheses are the only effective methods for producing homogenous glycans. To simplify glycan synthesis, we developed a programmable one-pot method for chemical synthesis of oligosaccharides and enzymatic synthesis with the regeneration of co-factors. We use the synthetic glycans in biological assays, glycan microarrays and for the development of therapeutic vaccines, and glycoengineering of proteins.

  • Cheng, C. W.; Zhou, Y.; Pan, W. H.; Dey, S.; Wu, C. Y.; Hsu, W. L.; Wong, C. H. "Hierarchical and programmable one-pot synthesis of oligosaccharides" Nat. Commun. 2018, 9, 5202. [Auto-CHO Software][GitHub]
  • Dey, S.; Lo, H. J.; Wong, C. H. "An Efficient Modular One-Pot Synthesis of Heparin-Based Anticoagulant Idraparinux" J. Am. Chem. Soc. 2019, 141, 10309-10314.
  • Huang, L.-Y.; Huang, S.-H.; Chang, Y.-C.; Cheng, W.-C.; Cheng, T.-J.; Wong, C.-H. "Enzymatic synthesis of lipid II and analogues" Angew. Chem. Int. Ed. Engl. 2014, 53, 8060-8065.
  • Shivatare, S. S.; Chang, S.-H.; Tsai, T.-I.; Tseng, S.-Y.; Shivatare, V.-S.; Lin, Y.-S.; Cheng, Y.-Y.; Ren, C.-T.; Lee, C.-C.; Pawar, S.; Tsai, C.-S.; Shih, H.-W.; Zeng, Y.-F.; Liang, C.-H.; Kwong, P.-D.; Burton, D.-R.; Wu, C.-Y.; Wong, C.-H. "Modular synthesis of N-glycans and arrays for the hetero-ligand binding analysis of HIV antibodies" Nat. Chem. 2016, 8, 338-346.

Homogenous Glycoproteins

Despite recent advances in genetic engineering of glycosylation pathways, the recombinant glycoproteins are generally obtained as mixtures of glycoforms making them unsuitable for functional studies. The Wong group was the first to realize enzymatic glycan remodeling to produce homogeneous glycoproteins demonstrating functional and structural differences between different glycoforms. The monoclonal antibody, immunoglobulin G, is one of the prominent glycoproteins, whose effector functions are regulated by N-glycosylation of Fc domain. In our group, we study the glycosylation of therapeutic monoclonal antibodies to improve their potency and pharmacokinetic parameters.

  • Witte, K.; Sears, P.; Martin, R.; Wong, C.-H. "Enzymatic glycoprotein synthesis:  preparation of ribonuclease glycoforms via enzymatic glycopeptide condensation and glycosylation" J. Am. Chem. Soc. 1997, 119, 2114-2118.
  • Culyba, E. K.; Price, J. L.; Hanson, S. R.; Dhar, A.; Wong, C.-H.; Gruebele, M.; Powers, E. T.; Kelly, J. W. "Protein native state stabilization by placing aromatic side chains in N-glycosylated reverse turns" Science 2011, 331, 571-575.
  • Lin, C.-W.; Tsai, M.-H.; Li, S.-T.; Tsai, T.-I.; Chu, K.-C.; Liu, Y.-C.; Lai, M.-Y.; Wu, C.-Y.; Tseng, Y.-C.; Shivatare, S.-S.; Wang, C.-H.; Chao, P.; Wang, S.-Y.; Shih, H.-W.; Zeng, Y.-F.; You, T.-H.; Liao, J.-Y.; Tu, Y.-C.; Lin, Y.-S.; Chuang, H.-Y.; Chen, C.-L.; Tsai, C.-S.; Huang, C.-C.; Lin, N.-H.; Ma, C.; Wu, C.-Y.; Wong, C.-H. "A common glycan structure on immunoglobulin G for enhancement of effector functions." Proc. Natl. Acad. Sci. U. S. A. 2015, 112, 10611-10616.
  • Lo, H. J.; Krasnova, L.; Dey, S.; Cheng, T.; Liu, H.; Tsai, T. I.; Wu, K. B.; Wu, C. Y.; Wong, C. H. "Synthesis of Sialidase-Resistant Oligosaccharide and Antibody Glycoform Containing alpha2,6-Linked 3F(ax)-Neu5Ac" J. Am. Chem. Soc. 2019, 141, 6484-6488.

Glycosylation Probes

The glycosylation probes are monosaccharides modified with a functional group (e.g., azide or alkyne), which could be labeled with a reporter tag using bioorthogonal chemistry. Metabolic incorporation of glycosylation probes allows monitoring of glycosylation processes in the cell and in vivo. By comparing the differences in labeling between healthy cells and cells affected by the pathology, we can identify the pathology-specific glycan biomarkers and develop new diagnostic tools, as well as discover new targets for the development of therapeutic agents. In our group, we are focusing on the alkyne-bearing probes with improved sensitivity and selectivity, as well as new bioorthogonal labeling reagents suitable for real-time imaging.

  • Sawa, M.; Hsu, T. L.; Itoh, T.; Sugiyama, M.; Hanson, S. R.; Vogt, P. K.; Wong, C. H. "Glycoproteomic probes for fluorescent imaging of fucosylated glycans in vivo" Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 12371-12376.
  • Kizuka, Y.; Funayama, S.; Shogomori, H.; Nakano, M.; Nakajima, K.; Oka, R.; Kitazume, S.; Yamaguchi, Y.; Sano, M.; Korekane, H.; Hsu, T. L.; Lee, H. Y.; Wong, C. H.; Taniguchi, N. "High-Sensitivity and Low-Toxicity Fucose Probe for Glycan Imaging and Biomarker Discovery" Cell Chem. Biol. 2016, 23, 782-792.
  • Tsai, C.-S.; Yen, H.-Y.; Lin, M.-I.; Tsai, T.-I.; Wang, S.-Y.; Huang, W.-I.; Hsu, T.-L.; Cheng, Y.-S. E.; Fang, J.-M.; Wong, C.-H. "Cell-permeable probe for identification and imaging of sialidases" Proc. Natl. Acad. Sci. U. S. A. 2013, 110, 2466-2471.
  • 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.

Glyco-enzyme Inhibitors

he inhibitors of glycan-processing enzymes could be used as probes to study glycosylation processes with the ultimate goal to develop new therapeutics. The enzymatic targets pursued in our group are comprised of influenza neuraminidase, bacterial transglycosylase, and mammalian b3GalT5. In our approach, we use both the substrate-based design of inhibitors and structure optimization of HTS hits.

  • Kizuka, Y.; Nakano, M.; Yamaguchi, Y.; Nakajima, K.; Oka, R.; Sato, K.; Ren, C. T.; Hsu, T. L.; Wong, C. H.; Taniguchi, N. "An Alkynyl-Fucose Halts Hepatoma Cell Migration and Invasion by Inhibiting GDP-Fucose-Synthesizing Enzyme FX, TSTA3" Cell Chem. Biol. 2017, 24, 1467-1478.
  • Wang, P. C.; Fang, J. M.; Tsai, K. C.; Wang, S. Y.; Huang, W. I.; Tseng, Y. C.; Cheng, Y. S.; Cheng, T. J.; Wong, C. H. "Peramivir Phosphonate Derivatives as Influenza Neuraminidase Inhibitors" J. Med. Chem. 2016, 59, 5297-5310.
  • 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.
  • Mitchell, M. L.; Tian, F.; Lee, L. V.; Wong, C. H. "Synthesis and evaluation of transition-state analogue inhibitors of alpha-1,3-fucosyltransferase" Angew. Chem. Int. Ed. Engl. 2002, 41, 3041-3044.

Glycan Arrays

Glycan microarrays are useful tools, in which the glycan arrangement mimics that of the cell surface taking into account the multivalent glycan-protein interactions. The Wong group pioneered the use of glycan microarray for the profiling of glycan-protein interactions and quantification of these interactions for biochemical studies and diagnostics. To improve the sensitivity of detection, we designed an aluminum oxide-coated glass slides for immobilization of glycan samples through phosphonate chemistry. In our laboratory, glycan arrays were used to identify cancer-specific glycan markers and discover an unusual hybrid-type N-glycan with high binding avidity to anti-HIV broadly neutralizing antibodies. The newly identified cancer-specific glycan biomarkers and glycan binders of anti-HIV antibodies are being investigated as haptens of the carbohydrate-based therapeutic vaccines.

  • Fazio, F.; Bryan, M. C.; Blixt, O.; Paulson, J. C.; Wong, C. H. "Synthesis of sugar arrays in microtiter plate" J. Am. Chem. Soc. 2002, 124, 14397-14402.
  • Wang, C. C.; Huang, Y. L.; Ren, C. T.; Lin, C. W.; Hung, J. T.; Yu, J. C.; Yu, A. L.; Wu, C. Y.; Wong, C. H. "Glycan microarray of Globo H and related structures for quantitative analysis of breast cancer" Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 11661-11666.
  • Chang, S. H.; Han, J. L.; Tseng, S. Y.; Lee, H. Y.; Lin, C. W.; Lin, Y. C.; Jeng, W. Y.; Wang, A. H.; Wu, C. Y.; Wong, C. H. "Glycan array on aluminum oxide-coated glass slides through phosphonate chemistry" J. Am. Chem. Soc. 2010, 132, 13371-13380.
  • Shivatare, V. S.; Shivatare, S. S.; Lee, C.-D.; Liang, C.-H.; Liao, K.-S.; Cheng, Y.-Y.; Saidachary, G.; Wu, C.-Y.; Lin, N.-H.; Kwong, P. D.; Burton, D. R.; Wu, C.-Y.; Wong, C.-H. "Unprecedented role of hybrid N-glycans as ligands for HIV-1 broadly neutralizing antibodies" J. Am. Chem. Soc. 2018, 140, 5202-5210.


Cancer progression is associated with the altered composition of glycolipids. In one of our studies, we established that globo-series glycans (Globo-H, SSEA-3, and SSEA-4) are found on the surface of 15 different types of cancers, including the breast cancer and breast cancer stem cells. Since these glycans are specific to cancerous cells and can stimulate an immune response, they are being investigated as haptens for therapeutic vaccines against cancer. Some of the disadvantages of carbohydrate-based vaccines include reduced immunogenicity and inability to generate a long-lasting response. Overcoming these challenges, we improved the formulation of Globo-H vaccine with diphtheria toxoid cross-reactive material 197 as an immunogenic carrier protein, and α-Gal ceramide C34 as an adjuvant to activate the IgM to IgG switch. In addition to vaccines for the treatment of cancer, our group is developing universal influenza vaccines and exploring different anti-HIV vaccine formulations based on the unique, virus-specific (i.e., gp-120-specific) N-glycan haptens.

  • 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.
  • Huang, Y.-L.; Hung, J.-T.; Cheung, S.-K.; Lee, H.-Y.; Chu, K.-C.; Li, S.-T.; Lin, Y.-C.; Ren, C.-T.; Cheng, T.-J.; Hsu, T.-L.; Yu, A.-L.; Wu, C.-Y.; Wong, C.-H. "Carbohydrate-based vaccines with a glycolipid adjuvant for breast cancer" Proc. Natl. Acad. Sci. U. S. A. 2013, 110, 2517-2522.
  • Tseng, Y. C.; Wu, C. Y.; Liu, M. L.; Chen, T. H.; Chiang, W. L.; Yu, Y. H.; Jan, J. T.; Lin, K. I.; Wong, C. H.; Ma, C. "Egg-based influenza split virus vaccine with monoglycosylation induces cross-strain protection against influenza virus infections" Proc. Natl. Acad. Sci. U. S. A. 2019, 116, 4200-4205.
  • Liao, H.-Y. ; Krasnova, L.; Wong, C.-H, "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. 117, 17757-63. 2020.

Group Members

    Postdoctoral Fellows

  • Chung-Yi WU
  • Hsin-Yu LIAO
  • Yen-Yu TSENG
  • Chi-Ying LIN
  • Yi-Wei LOU
  • Cheng-Wei CHENG
  • Yu-Ya KAO
  • Chen-Yo FAN


  • Sylvia LIN

    Research Assistants

  • Ting-Yen LAI
  • Wan-Yu CHEN
  • Chih-Chuan KUNG

    Ph.D. Students

  • Szu-Wen WANG
  • Cai-Rong JIANG
  • Nai-Yu CHEN
  • Shan-He CHEN
  • Cheng-Hsiung CHEN

    Graduate Students

  • Kuang-Cheng LEE
  • Yu-Jen WANG
  • Jia-Yan CHEN

    Undergraduate Student

  • Ashley Jia-Yi HUANG


Professor Chi-Huey WONG

Distinguished Research Fellow, Genomics Research Center, Academia Sinica
128 Academia Road, Section 2, Nankang, Taipei, Taiwan [Google Map]
Tel: +886-2-2789-9929
Fax: +886-2-2789-9927
E-mail: or

Ms. Sylvia LIN


Professor Chi-Huey WONG's Laboratory, Genomics Research Center, Academia Sinica, Taiwan