Dr. Wang’s laboratory is working at the interface of chemistry and biology with a focus on understanding the functional roles of oligosaccharides and glycoproteins in biological system. Protein glycosylation, the covalent attachment of sugars, is one of the most ubiquitous posttranslational modifications of proteins in eukaryotic cells. More than two third of total proteins in human body are glycosylated. The oligosaccharide components have been implicated to play pivotal roles in a number of important biological recognition processes, such as cell adhesion, cell differentiation, development, tumor progression, host-pathogen interaction, and immune response. Abnormal glycosylations are frequently associated with diseases, which can serve as novel biomarkers for diagnosis or as targets for drug and vaccine design. Nevertheless, due to their functional diversity and structural complexity, we are only beginning to unveil the mysteries of this important class of bio-molecules. Dr. Wang’s laboratory combines synthetic chemistry, structural biology and immunology to decipher the functions of oligosaccharides and glycoproteins. The knowledge gained from the fundamental studies is applied for drug discovery and vaccine design.
Current research in the laboratory is focused on three areas:
Schwarz, F., Huang, W., Li, C., Schulz, B. L., Lizak, C., Palumbo, A., Numao, S., Neri, D., Aebi, M., Wang, L. X. “A combined method for producing homogeneous glycoproteins with eukaryotic N-glycosylation”, Nature Chemical Biology, 6, 264-266 (2010).
Umekawa, M., Li, C., Higashiyama, T., Huang, W., Ashida, H., Yamamoto, K., Wang, L. X., “Efficient glycosynthase mutant derived from Mucor hiemalis endo-beta-N-acetylglucosaminidase capable of transferring oligosaccharide from both sugar oxazoline and natural N-glycan”, Journal of Biological Chemistry, 281, 511-521 (2010).
Yang, Q., Li, C., Wei, Y., Huang, W., Wang, L. X., “Expression, glycoform characterization, and antibody-binding of HIV-1 V3 glycopeptide domain fused with human IgG1-Fc”, Bioconjugate Chemistry., 21, 875-883 (2010).
Huang, W., Yang, Q., Umekawa, M., Yamamoto, K., Wang, L.X., “Arthrobacter endo-beta-N-acetylglucosaminidase shows transglycosylation activity on complex type N-glycan oxazolines. One-pot conversion of ribonuclease B to sialylated ribonuclease C”. ChemBioChem, 11, 1350-1355 (2010).
Huang, W., Wang, D., Yamada, M., Wang, L. X., “Chemoenzymatic synthesis and lectin array characterization of a class of N-glycan clusters”, Journal of the American Chemical Society, 131, 17963-17971 (2009).
Huang, W., Li, C., Li, B., Umekawa, M., Yamamoto, K., Zhang, X., Wang, L. X., “Novel glycosynthases enable a highly efficient chemo-enzymatic synthesis of N-glycoproteins carrying intact natural N-glycans”, Journal of the American Chemical Society, 131, 2214-2223 (2009).
Wei, Y., Li, C., Huang, W., Li, B., Strome, S. E., Wang, L. X., “Glyco-engineering of human IgG1-Fc through combined yeast expression and in vitro chemoenzymatic glycosylation”, Biochemistry, 47, 10294-10304 (2008).
Ochiai, H., Huang, W., Wei, Y., Wang, L. X., “Expeditious chemoenzymatic synthesis of homogeneous N-glycoproteins carrying defined oligosaccharide ligands”. Journal of the American Chemical Society, 130, 13790-13803 (2008).