Wednesday, January 17, 2024 - 4:00pm

Abstract: Nature regulates many biological processes through post-translational modifications that modify protein activity and relay signals through protein networks. Interpretation of how nature uses these modifications will provide new insights to biological regulation, and open new frontiers in the design of therapeutic modalities that mimic nature to treat human disease. We combine probe development and protein engineering with chemical proteomics to address key challenges in reading and rewriting post-translational modifications, with a focus on the nutrient sensor O-linked N-acetyl glucosamine (O-GlcNAc) and the C-terminal cyclic imide marker of protein damage. In parallel, we investigate chemical ligands that modify protein function to probe for natural regulatory events in biological systems. Here, I will describe our efforts to study the C-terminal cyclic imide, an overlooked post-translational modification, as a degron for the E3 ligase adapter cereblon (CRBN), which has opened new directions in E3 ligase biology and novel ligand discovery. I will also update on current efforts to understand where, when, and how the C-terminal cyclic imide degron occurs and its biological connection to the physiological function of CRBN.


Christina Woo


Harvard University


RH 104