Our group investigates the biological roles of glycan-binding proteins (GBPs) involved in the virus infection and immune responses. By combining the tools/concepts of chemistry, biology, virology and immunology, we focus on understanding the interaction mechanisms between GBPs and their glycan ligands, which guide us to develop synthetic probes to target or manipulate the celluar processes.

1. Understanding the Catalytic Mechanism of Glycosyltransferases

Glycans decorate the surfaces of all living cells and comprise highly diverse structures that mediate a wealth of biology through GBPs, e.g. lectins and anti-glycan antibodies, that recognize them as ligands. In contrast to DNA, RNA and proteins, glycosylation is a non-template driven enzymatic modification process in ER and Golgi apparatus that allows for glycan attachment, trimming, chain elongation and branching as well as glycan derivatization. This project primarily focuses upon understanding the catalytic mechanism of glycosyltransferases (GT) involved in the glycosidic bond forming, which guides us to expand the subsrate scope and improve the catalytic activity via a rational design strategy.

 

Example: Sialyltransferase transfers a sialic acid residue to terminal Gal of glycoprotein or glycolipid.

2. Investigation of the Biological Roles of Glycans in the Microbe Infection

Investigations of the interactions between glycans and GBPs have greatly advanced our understanding of the molecular basis of these fundamental processes. However, due to the non-template biosynthetic process, glycans are dynamically dispalyed on cell surface, resulting in heterogenous and complex glycome. Our group aims to develop a novel glycan microarray by chemoenzymatic synthesis cover the structural diversity needed for the biological problem of interest, e.g. identification of natural ligands for viral lectins in a high-throughput screening manner. These identified ligands could be applied to intervene the interactions between glycans and lectins, providing information that simultaneously illuminates the biology mediated by them and decodes the informational content of the glycome.

 

Microscope glass slide-based glycan microarray was developed to mimic glycans dispalyed on cell surface.

3. Targeting Glyco-immune Checkpoint

Sialic acid–binding immunoglobulin-like lectins (Siglecs) are expressed on the majority of white blood cells of the immune system and function as cell signaling co-receptors helping the immune system distinguish between self and nonself. Because of their restricted cell type expression and roles as checkpoints in human diseases such as cancer, asthma, allergy, neurodegeneration, and autoimmune diseases, Siglecs have gained attention as targets for therapeutic interventions. Our group aims to employ Siglec high affinity ligands (sialic acid memetics) to block the Sia-Siglec axis for reactivating the immune cells to increase the antitumor activity or targeting tumor cells.

 

Siglec high affinity ligands decorated nanoparticles or effect cells target tumor cells via Siglec-Sia axis.