Jeffrey M. Peters PhD

Research:

Our laboratory studies the role of the peroxisome proliferator-activated receptors (PPARs) in the regulation of homeostasis, toxicology and carcinogenesis. PPARs are members of the nuclear receptor superfamily and are critical modulators of environmental and dietary stimulii. For example fatty acids and metabolic derivatives of fatty acids derived primarily from dietary sources are known ligands that can activate PPARs. Moreover, environmental chemicals can also activate PPARs, such as perfluorinated chemicals and phthalate monesters that are currently a major health concern. 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, PPARβ/δ and PPARγ ligands/activators, and are clinically relevant for a number of diseases including diabetes, obesity, atherosclerosis and cancer. In addition to transcriptional regulation, PPARs can also epigenetically regulate transcription by interacting with other proteins including NF-κB. Our laboratory uses “knockout”, transgenic mouse models, and high affinity agonists and antagonists to delineate the roles of PPARs, with a particular interest in epithelial and liver cancer. Through our studies, we are elucidating the molecular mechanisms by which exogenous (dietary) and endogenous (metabolic sources) lipids specifically modulate human health. We are particularly interested in delineating how natural compounds found in dietary constituents can activate PPARs with the goal of identifying new molecules/proteins that can be targeted with existing approaches to improve the efficacy of chemoprevention and chemotherapy. Our studies will likely lead to the identification of specific macronutrients that will effectively activate PPARs so that dietary formulations of agricultural products can be developed that will improve human and animal health and prevent serious diseases.