Our research is focused on the synthesis of complex glycoproteins, natural products, and oligosaccharides of importance in immunology and oncology. We focus on projects where synthetic chemistry can make defined and powerful contributions toward solving challenging problems in translational science and medicine. By making difficult chemistry accessible through new strategies and synthetic methods, we can accelerate biological interrogation and medicinal chemistry efforts. This is especially relevant in the context of molecules or material unreachable through isolation or expression-based methods. It is our long-term goal to identify lead structures that will have a major impact as pharmacological tools and potential therapeutics.
Often referred to as 'biologics’, glycoproteins are now an established class of therapeutic macromolecules utilized in medicine. Our laboratory is actively involved in the synthesis of single isoform, glycosylated peptides. Representative projects include the design of ovarian cancer-related epitopes utilized for antibody generation against aggressive tumors, the synthesis of hybrid diabodies capable of macrophage reprogramming in both cancer and autoimmune diseases, and preparing disease-specific targeted FOXO transcription factors as new types of therapeutics. As an extension of our interest in the synthesis and chemical biology of glycoproteins, we are focusing on developing new catalytic amide bond-forming reactions as part of this program.
Oligosaccharides mediate complex signaling events in the body, and demonstrate manifold biological activities. We are investigating the synthesis of unusual carbohydrate constructs with potential to invigorate stalled immune responses in individuals with chronic infections and cancer. We are specifically focusing on the activation of dendritic cells, natural killer (NK) cells, and T cells though auxiliary stimulation mechanisms, independent of major receptor-induced activation.
Small Molecule Chemistry
By developing concise platforms to biologically active, structurally-complex natural products, we can enable more rapid investigation into their pharmacology and potential therapeutic development. Our laboratory is pursuing the synthesis of both immunomodulatory and anti-cancer molecules possessing novel mechanisms of action, with an emphasis on pancreatic and lung cancers. Importantly, our approaches to these natural products will be able to produce edited analogues for identifying structure-activity relationships and be capable of incorporating radiolabeled probes for imaging and diagnostic purposes.