C. elegans as a model for studying the regulation of FoxO transcription factors in development and aging
We use the nematode C. elegans as a model system to study evolutionarily conserved signal transduction pathways that are dysregulated in human disease, with the ultimate goal of generating hypotheses that can be tested in mouse models of disease. Our current work is focused on a conserved insulin-like growth factor (IGF) pathway that regulates development, metabolism, and longevity in C. elegans. Many components of IGF-1 signaling are mutated in human cancers, and mice harboring knockout alleles of genes in the insulin signaling pathway develop insulin-resistant diabetes. We have discovered a new conserved pathway, the EAK pathway, that acts in parallel to PI3K/Akt signaling to regulate the FoxO transcription factor DAF-16. Emerging data in mouse models of human disease indicate that FoxO transcription factors may play a role in the pathogenesis of aging-associated diseases such as cancer, Type 2 diabetes, and osteoporosis. We are currently exploring mechanisms of EAK pathway action in C. elegans and plan to extrapolate our findings to mouse models of human disease.