The scientific goals and central themes of the Mouse Models and Cancer Stem Cells Program are to investigate different aspects of stem cell function, including self renewal, reprogramming, and dedifferentiation and differentiation, using mouse, Drosophila, Xenopus, and zebrafish as models, with the goal of learning more about embryonic, tissue and cancer stem cells. Linked to this are major efforts to use induced pluripotent stem cell (iPSC) technology to study mechanisms of genomic reprogramming, including changes in DNA methylation patterns, to learn how cancer stem cells might arise through genomic reprogramming, and to develop "disease-in-a dish" models of human diseases. Developmental signaling pathways that are often reactivated and used to drive cancer cell phenotypes are being studied, including the Wnt/p-catenin pathway, the ERBB2, RET, and TAM receptor tyrosine kinases, and TGF-p pathways. The development and use of mouse models to study cancer biology and the role of inflammation in carcinogenesis are also important goals, and also to utilize lentivirus vectors for cancer therapy and for development of new cancer models. The program includes twelve members from eight different Laboratories (Departments), see the following page for a list of personnel. The NCI and other peer-reviewed cancer related support (direct costs) for the last budget year was $10,760,318. The substantial NIH and other federal support for this program is outlined in the table of externally funded research projects. The total number of cancer-relevant publications by members of this program in the last grant period (2008- 2012) was 237. Of the total publications, 7% were intraprogrammatic and 12% were interprogrammatic.

RELEVANCE (See instructions): The study of human cancer requires the development of animal models that recapitulate human disease. This program will focus on development of mouse models and stem cell approaches to studying cancer.