Chemistry and Biochemistry
Nanotechnologies for analysis of glycan function during development. Glycomaterials for stem cell-based tissue regeneration.
The field of glycobiology is gaining in importance as new discoveries continue to reveal the fundamental contributions of glycans (also called carbohydrates, saccharides, or, simply, sugars) in biology. Cell-surface and extracellular matrix glycoconjugates govern myriad biological processes intimately linked to healthy development as well as the onset and progression of many diseases. Glycans are typically organized on polypeptide scaffolds in patterns that encode protein-binding motifs. The patterns span tens to hundreds of nanometers and it is the nanoscale encoding of information by glycans (and their exclusion from the direct purview of the Genome) that makes them elusive to interrogation by traditional genetic and biochemical methods. Our group combines synthetic chemistry approaches with concepts of nanoscience to generate glycomaterials that match the dimensions and sophistication of native glycoconjugates and can be used to intercept, analyze, and dynamically perturb signaling pathways controlled by these biomolecules.
The two classes of glycoconjugates under investigation in our lab are proteoglycans and mucins. Proteoglycans are known regulators of growth factor signaling during development. We are interested in creating functional surrogates of proteoglycans and using them to guide embryonic stem cell differentiation into specific tissue lineages with an eye toward regenerative medicine applications. Mucins are linear heavily glycosylated proteins forming a protective mucous layer on epithelial surfaces lining many of our organs. Outside of their protective function, mucins mediate cellular signaling and communication by engaging surface receptors via their glycan ligands. Our lab uses a novel screening platform comprising microarrayed libraries of structurally well-defined synthetic mucin mimetics to systematically profile the role of specific glycan structures and their nanoscale presentation in the context of maintenance of proper mucous barrier function and in modulating pathogen adhesion to epithelial surfaces.