Elucidating the role of glycans in human disease requires:
Design of Chemical Tools
Cellular Biology &
Glycans are oligosaccharides (sugars linked together). Glycans are densely arrayed on the cell surface, playing many biological roles. Studying the biological roles of these glycans is the field of glycobiology.
Conventional methodologies and approaches are often insufficient in tackling roles for glycans in biology. Our laboratory takes an original approach that leans heavily on chemical biology in the study of glycobiology.
Siglecs (Sialic acid-binding immunoglobulin-type lectins) are cell surface proteins that bind sialic acid.
We uses a combination of the chemical, biochemical, and genetic strategies to probe the roles of glycans, through the Siglecs, in modulating immune responses. From these fundamental observations, strategies can be designed to modulate immune cells.
Siglec-glycan interactions is are weak. This makes it difficult to study them outside of the context of a cell-cell interactions, where the ‘velcro effect’ (avidity) is at play. The second challenge relates to the chemical complexity of glycans.
Overcoming These Challenges:
1. Developing tools to study Siglec-glycan interactions that mimic the natural avidity of Siglecs
2. Applying chemical biology approaches to distill down the chemical complexity of glycans.
Liposomes and Bacteriophage
Siglec probes containing a chemical handle allows for rapid and bio-orthogonal reactions.
These next-generation tools will help researchers uncover critical new roles played by Siglecs and carbohydrates in controlling the function of immune cells.
small molecule inhibitors
Small molecule inhibitors of glycan-processing enzymes are used to manipulate glycan structures
Our lab develops small molecule inhibitors that modulate the activity of the key enzymes that make Siglec ligands in cells called sialyltransferases.