My laboratory uses the mouse as an experimental genetic model to investigate factors that contribute to inter-individual differences in health and disease. Our current research activities include the identification and functional characterization of alleles contributing to cancer susceptibility, the function of the Erbb gene family in development and disease, and the role of genetic variation in response to environmental stimuli. To support these investigations, we also are developing new genetic tools to support mammalian systems genetic approaches to phenotypes with complex genetic and environmental etiologies. Cancer genetics: We are focusing on colorectal and breast cancer to identify environmental factors and genetic polymorphisms contributing to differential susceptibility to the development and progression of cancer. We are also developing approaches to exploit these factors to prevent or delay cancer as well as to identify new therapies. Epidermal growth factor receptor (Egfr): We are using mouse models with genetically engineered or spontaneous mutations to elucidate the biological role of Egfr and other member of the Erbb gene family in vivo. These studies have lead to new insights into the role of these genes in neuronal survival and behavior, obesity, cancer and cardiovascular disease. We are currently performing mechanistic studies to identify how the Erbb genes contribute to normal and abnormal phenotypes. Genetics of environmental response: Just as individuals differ in their genetic constitution and disease susceptibility, they also differ in their responses to exogenous stimuli. We are using mouse models to investigate responses to environmental factors like the enteric flora of the gastrointestinal tract and diet and toxicants like dioxin and trichloroethane. The goal of these studies is to identify how individual responses to environmental factors leads to differential disease susceptibilities. Systems genetics resources: We are leading a large international effort to develop and exploit a new mouse genetic resources that will support the integration of genetics into systems biological analyses at the whole animal level. These efforts are based upon the Collaborative Cross, which is a unique recombinant inbred population of mice that have randomly assorted the genetic polymorphisms present in the eight founder inbred strains.