IDENTIFYING SMALL MOLECULES AS CHEMICAL DRIVERS OF HEALTH AND DISEASE

ROUTES OF HUMAN EXPOSURE TO ENVIRONMENTAL CONTAMINANTS

 

An aspect of our research explores whether we are exposed to organic pollutants from their presence in the indoor environment, with focus on emerging per- and polyfluoroalkyl substances (PFAS). We use targeted LC-MS/MS and GC-MS methods to measure levels of these compounds and their transformation products. Current research projects in this area measure PFAS in household dust, a common sink and source of exposure for many kinds of environmental contaminants, as well as those in our diet and personal care products.

BIOLOGICAL FATE AND TRANSFORMATION

 

Once exposed to contaminants, the body has mechanisms in place to eliminate them. Our research in this area identifies enzymes responsible for PFAS metabolism, with focus on cytochrome P450s (CYP). We also examine the contribution of extrahepatic enzymes to PFAS transformation, as well as CYP that are localized on specific intracellular membranes. In most cases, CYP transform contaminants to compounds that are eliminated from the body, but metabolism can also lead to more toxic and/or persistent products. We use in vivo techniques with the nematode C. elegans, and in vitro techniques with subcellular microsome and cytosol fractions, as well as recombinant enzymes, to examine metabolism of this varied class of chemicals.

EFFECTS ON LIPID SIGNALING AND MODULATORS OF CONTAMINANT ACTION 

 

Oxidized lipids are chemical messengers in cells that regulate the body’s normal function. Some pollutants interfere with or disrupt the normal body functions controlled by oxidized lipids, such as inflammation and cell homeostasis. This can contribute to toxic effects and onset of chronic diseases including cancer. We use C. elegans and cell culture to explore the mechanisms by which contaminants interfere with these processes, leading to disease. We couple these models with LC-MS/MS methods to analyze several oxidized lipid classes, as well as biochemical methods for protein measurements. We also address the interaction between different kinds of environmental stressors that may alter relationships between exposure and effect.