Principal Investigator Matthew Shoulders
The unfolded protein response (UPR) is responsible for maintaining proteostasis in the endoplasmic reticulum (ER). Aside from its role as a protein folding and quality control factory, another important function of the ER is asparagine N-glycosylation, engendering diverse and important sugar modification patterns on proteins. Using our chemical genetic methods to probe proteostasis, we uncovered a previously unknown function of the UPR—regulating the molecular architecture of ectopically expressed secreted and endogenous cell-surface proteins by altering N-glycan maturation patterns. We are exploring the mechanistic origins of this observation, and its consequences for normal physiology, cancer, and innate immunity.