Start: November 13, 2025 3:30 p.m.
End: November 13, 2025 4:30 p.m.
Light-activated chemical tools and reactions for studying sugar-based processes in cells and disease
Dr. Charlie Fehl
Assistant Professor, Department of Chemistry, Wayne State University
Thursday, 11/13 @ 3:30 PM
FB 253
Unlike many chemical activation methods, photochemistry can be applied in living cells to modulate biological processes with minimal disruption. We leverage light-driven uncaging to develop "PhotoSugar" probes for studying sugar metabolites, including N-acetylglucosamine (GlcNAc), N-acetylgalactosamine (GalNAc), and sialic acids, and their effects on cellular signaling. Using these probes, we found that releasing GlcNAc in cells increases O-linked GlcNAc protein modifications through the enzyme O-GlcNAc transferase (OGT). These modifications alter protein behavior, including subcellular localization between the nucleus and cytoplasm. Unexpectedly, we also discovered that some of our PhotoSugar compounds inhibit OGT itself. Through computational re-design, synthesis, and medicinal chemistry assays, we identified a new scaffold of OGT inhibitors. In parallel, we developed a novel photocatalyzed thiol–ene reaction that enables rapid access to substituted thiosugars. Together, our approaches—photocaged metabolites, enzyme inhibitors, and new synthetic methods—bridge chemistry and biology to uncover how sugar metabolites shape signaling, metabolism, and disease.