Research
The glycocode, or combinatorial patterns of glycosylation that relay biological information, functions in essential roles that govern human health and myriad diseases (e.g., cancer, infectious diseases, autoimmune diseases). However, we lack fundamental insights into how the glycocode contributes to biological function at a molecular level. Our perspectives on the glycocode remain deficient because the non-templated complexity of glycosylation creates analytical challenges that have severely limited our ability to study glycoconjugates.
Our group aims to solve these challenges.
We leverage state-of-the-art mass spectrometry and chemical glycobiology to develop innovative technologies for investigating essential principles of glycocode regulation and dysregulation. Specifically, we are interested in understanding how altered cell surface phenotypes (i.e., glycocalyx status) manifest in cancer progression and drive metastasis. Through a combination of MS-based multi-omics, bioinformatics, and chemical biology, our goal is to use a systems-level approach to glycobiology to further our understanding of human health and disease and advance therapeutic glycoscience.
Mapping glycoconjugates in health and disease
Cell surface glycoconjugates contain remarkable heterogeneity, much of which remains to be defined. We lead efforts to map cell-surface glycosylation using innovative MS-centric approaches to characterize glycopeptides and glycans, including custom enrichment platforms, informatic strategies to improve MS data acquisition and post-acquisition analyses, and tools to integrate highly dimensional datasets.
Unique molecular surfaces of glycoproteins
Individual glycocode features combine to form holistic molecular surfaces that govern biological function. Thus, the glycocode must be captured from the top-down to resolve combinatorial patterns. We develop technologies to characterize intact glycoproteins that complement bottom-up mapping efforts, including gas-phase ion-ion chemistries, tandem MS strategies, and structural glycoproteomic approaches to determine higher order structures that govern glycoprotein interactions with other biomolecules.
Glycosylation and secretion in metastasis
Tumor cells exert influence on local and peripheral tissue environments through secreted or shed proteins, collectively known as the secretome; however, the roles of these proteins in metastasis remain poorly understood. Altered glycosylation states, a hallmark of cancer, are intimately linked with secretion, but mechanisms that tether the two remain underexplored. We combine chemical biology with MS-centric technologies to study functional links between regulatory secretome events, aberrant glycosylation, and metastatic progression.
