Research Interests

My lab is broadly focused on the chemistry of proteins, both the methods to synthesize and modify them and the chemistry of their folding, stability, ligand binding and catalysis. Proteins are simple in formula but complex in functionality, a characteristic that has confounded their manipulation by traditional synthetic organic approaches. I have endeavored to apply simple chemistry to these complex molecules under the guiding principle of using chemoselectivity and regioselectivity to facilitate specific chemical reactions on unprotected proteins under neutral aqueous conditions. Many of my lab’s most significant advances have come from detailed understanding of fundamental functional group reactivity in aqueous solution, drawing lessons from classical studies in physical organic chemistry and enzymology and I have applied insights from these studies to develop powerful new methods for the synthesis of complex macromolecules. The flip side of this methodology development is the utilization of solid phase peptide synthesis (SPPS), a powerful yet protecting group intensive strategy for the synthesis of the raw material polypeptide chains that we use to assemble proteins. Drawing from a rich history of SPPS optimization and refinement, I have pioneered robust solutions for the considerable challenge of C-terminal activation of peptides following chain assembly, providing the essential intermediates for protein synthesis by NCL and other fragment based assembly methods. We have utilized these synthetic methods to broadly advance protein science focusing on areas such as protein and nanoparticle engineering and viral immunogen design.