Our laboratory studies the role of the peroxisome proliferator-activated receptors (PPARs) in the regulation of homeostasis, toxicology and carcinogenesis with extensive application of null mouse models. PPARs are members of the nuclear receptor superfamily and are critical modulators of environmental and dietary stimulii. Acting as regulatory transcription factors, the PPARs modulate gene expression of target genes containing peroxisome proliferator responsive elements in response to ligand activation. Numerous genes that modulate lipid metabolism are regulated by PPARα and PPARγ ligands/activators, and are clinically relevant for a number of diseases including diabetes, obesity, atherosclerosis and cancer. Our laboratory uses “knockout” and transgenic mouse models to delineate the roles of PPARs, with a particular emphasis on epithelial cancers. Our goal is to identify new molecules/proteins that can be targeted with existing approaches to improve the efficacy of chemoprevention and chemotherapy.