Novel lipid signaling pathways
The essential ω-3 and ω-6 fatty acids metabolize by lipoxygenase, cytochrome P450, and cyclooxygenase families to form oxidized lipids called oxylipins. Oxylipins act as signaling molecules that have far ranging physiological effects and the enzymes responsible for their production are the targets of many pharmaceuticals. There is cross-talk between these metabolic pathways, resulting in the formation of novel lipids with relatively unknown biological activity. We use a combination of mass spectrometry and culture models to characterize these novel pathways and elucidate their biological activity, filling knowledge gaps in how these lipid mediators affect our health, and study the consequence of their modification by environmental pollutants.
Recently completed project: Angiogenesis is enhanced by a lipid signaling molecule derived from ω-6 fatty acids
Molecular mechanisms of environmental contaminant exposure
We aim to understand the impact emerging contaminants have on the lipid metabolome and subsequent influence on fundamental cellular processes. Our current focus is on the polyfluoroalkyl substances, given their global presence in humans, wildlife, and the environment. Classes of these substances metabolize to form electrophilic intermediates capable of binding to proteins, changing fundamental cell processes regulated by proteins, genes, and lipids. By pairing biochemical analysis to measure changes of proteins or transcriptional RNA, with LC-MS/MS to probe changes in lipid signaling pathways, we can more completely understand the effect contaminants have on physicological processes. We evaluate basic (cell stress) and higher order (angiogenesis) physiological processes, establishing the need to consider lipid metabolomics with respect to contaminant exposure, crucial for protecting human and environmental health.
Recently completed project: Fluorinated substances metabolize to bioactive products that covalently modify proteins