Dr. Rutkowski seeks to understand how the endoplasmic reticulum (ER) regulates lipid metabolism in hepatocytes in the setting of chronic stress. His group demonstrated that perturbations of the ER disrupt lipid metabolism by the liver, and that this leads to fat accumulation (steatosis). His group is determining how activation of the unfolded protein response (UPR) during fasting/feeding cycles contributes to normal homeostatic regulation of lipid metabolism, and how the inhibition of fatty acid beta-oxidation by the UPR protects ER functions. Hepatic steatosis is a complication in CF patients and ferrets, and may contribute to altered glucose metabolism in CFRD.