glycobiology medicinal chemistry carbohydrate chemistry bioconjugate chemistry
BSc, State University of New York - Albany (1996)
PhD, University of Wisconsin - Madison (2002)
NIH PDF, Harvard Medical School (2006)
Research In the Lab
Cell surface receptors mediate the transfer of information between cells and their environment. As a result, receptors play vital roles in all aspects of cell biology including development, immune response, homeostasis, and pharmacology. Although many receptor systems have been intensely studied, fundamental questions about their molecular function remain unanswered. Research in our group uses chemical biology to improve our mechanistic understanding of membrane biology and develop new tools for therapeutic strategies. Specific areas of research include:
Glycolipids and glycoproteins are a critical components of the plasma membrane. In addition to biosynthetic pathways, glycan content is regulated by glycosyl hydrolases. Our group has been investigating the role of the membrane-associated neuraminidases (NEU; also called sialidases).
Using recombinant forms of NEU enzymes we have developed structure-activity relationships for inhibitors and substrates of human NEU isoenzymes (NEU1, NEU2, NEU3, NEU4). Using this approach, we have developed specific inhibitors with excellent selectivity for individual enzymes. Work is currently focused on improving these compounds for therapeutic applications.
Current projects are investigating the role of NEU enzymes in cell migration, cell adhesion, and inflammation.
Synthetic strategies for controlled modification of biomolecules in vitro or in cells is a rapidly evolving area of chemical biology. Our group is interested in the development and application of new labeling strategies that provide access to modified lipids, glycolipids, proteins, and glycoproteins. We have previously used metabolic labeling as well as chemical and chemoenzymatic synthesis for these systems.
Current projects in the group are applying chemoenzymatic and bioconjugate strategies to unusual glycoproteins.
Phosphatase enzymes are the biochemical antithesis of kinases – removing phosphate groups from proteins and other biomolecules. While kinases have become a common target for drug development, phosphatases have seen limited applications in medicinal chemistry. Our group previously developed a modular strategy for designing protein tyrosine phosphatase inhibitors using solid-phase peptide synthesis (SPPS). We have also applied similar chemical strategies to glycosyl phosphatase substrates important for diabetes.
Current projects in the group are testing the utility of alpha-bromobenzyl phosphonates in the structural biology of PTPase enzymes.