Research & Interests
Our lab is interested in the mechanisms through which the physical properties and regulatory actions of specific lipids impact the cell biology and physiology of animals. The implications of this research extend from understanding how specific fatty acids affect cell signaling to dissecting the fat regulatory pathways involved in obesity and related diseases. We use the nematode model Caenorhabditis elegans and a combination of genetic, genomic and biochemical approaches to understand the regulation, function and biosynthesis of unsaturated fatty acids.
Genetic pathways of fat storage
Animals deficient in stearoyl-CoA desaturase have reduced fat content. We are currently using C. elegans mutants to examine how fatty acid desaturase pathways interact with other metabolic pathways that regulate fat storage. We have identified transcriptional regulators of stearoyl-CoA desaturase, including several nuclear hormone receptors and SREBP (sterol repeat element binding protein). These important regulators of lipid homeostasis are involved in the end-product feed-back regulation of transcription of lipid metabolism genes in mammals. Studies of these proteins in C. elegans contribute to the understanding, and possibly the future manipulation, of fat regulatory pathways involved in obesity and related diseases.
Functions of polyunsaturated fatty acids
Unsaturated fatty acids play vital roles as structural components of membranes and as signaling molecules. We have isolated C. elegans mutants with altered capacity to synthesis unsaturated fatty acids. These mutants provide new tools to understand the roles unsaturated fatty acids in membrane biology and cell function. We discovered that dietary supplementation with an omega-6 long-chain polyunsaturated fatty acid, DGLA (20:3n-6), causes defects in the development and maintenance of germ cells. Nematodes feeding on DGLA, but not other long-chain polyunsaturated fatty acids become sterile, partly due to excess apoptosis of germ cells. Our molecular, genetic, and biochemical studies of this process promise to shed light on the roles of polyunsaturated fatty acids in reproductive processes.