Interests: Carbohydrates; glycobiology; Golgi; membrane proteins; chemical biology
In 2012, the National Academy of Sciences published an expert report titled, "Transforming Glycoscience: A Roadmap for the Future." The central theme of this report is that "[a] new focus on glycoscience, a field that explores the structures and functions of sugars, promises great advances in areas as diverse as medicine, energy generation, and materials science... [h]owever, glycans have received little attention from the research community due to lack of tools to probe their ofter complex structures and properties." Research in our laboratory tackles this challenge. We develop new chemical biology approaches and conduct molecular dissection of glycan function.
In early work, we developed photocrosslinking sugar analogs of sialic acid and GlcNAc that can be metabolically incorporated into cellular glycoconjugates and used to identify transient glycan-mediated interations. Using the photocrosslinking sialic acid analog, we discovered novel and functionally significant fucosylated binding partners for cholera toxin. We share our reagents and expertise with many research groups. One reagent (Ac4ManNDAz) that we developed is now commercially available.
We continue to study the glycan binding specificities of bacterial toxins, as well as the mechanisms by which these toxins enter host cells and impact host cell function. Additional current efforts focus on investigating mechanisms that regulate glycoconjugate biosynthesis, controlling features such as the length of glycan chains and the degree of fucosylation. We recently identified B3GNT7 as an important regulator of mucin glycosylation in the intestinal epithelia, sparking interest in this understudied enzyme. Our long-term goals are to determine how glycan features vary among individuals and their association with disease states.
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