Jeremiah P. Freeman Organic Syntheses Lectureship
"Rewriting Protein Modifications"
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 frontiers in the design of therapeutic modalities that mimic nature to treat human disease. We combine chemical probe development and protein engineering with chemical proteomics to address key challenges in reading and rewriting post-translational modifications. Our efforts have focused on the nutrient sensor O-linked N-acetyl glucosamine (O-GlcNAc) and the C-terminal cyclic imide marker for protein degradation through the E3 ligase substrate adapter cereblon. Here, I will share how the investigation of cereblon ligands used in the clinic have enabled an understanding of the physiological function of cereblon and the discovery of new regulatory processes in our cells.