My primary research interest is in the pathology of animal models, especially models of cancer and aging. I am a D.V.M, Ph.D and Diplomate of the American College of Veterinary Pathologists. I have been continuously working on comparative/veterinary pathology for 34 years. I have been doing primarily mouse pathology for 29 of those years. During that time, as a PI and as a collaborator, I have done extensive studies in general and experimental pathology, cancer pathology, pathology of aging, transgenic animal pathology, developmental biology, general rodent pathology, immunology, and genetics. I started working with mutant mouse models (Foxp3) in 1987 and GEMMs (PKD) in 1989. In my role as Phenotyping Core Director and veterinary pathologist for research animals at the University of Michigan (UM), I have had the opportunity to see a vast spectrum of cancer, aging, and related pathology. Recently, I have been primarily committed to 1) studies of genetic models of cancer at the University of Michigan, Cold Spring Harbor Laboratory (CSHL), and Memorial Sloan-Kettering Cancer Center (MSKCC) and 2) pathology of aging with the NIA NTP program and the University of Washington. Three decades of doing mouse pathology are a great advantage in the correct analysis of animal models of aging and cancer. The differences in mice and humans, strain effects, sex effects, background lesions, and spontaneous and aging lesions in the mouse can be confusing to a novice. Furthermore, mouse models sometimes have different morphologic characteristics than the same cancer in humans. However, the cancers in animal models generally share all the relevant biology, genetics, and response to manipulation, which makes them valid models. In a few cases, the morphology and complex biology cannot be completely reproduced in the mouse due to inherent differences in mice and humans and interpretation of the pathology and biology are more complex. For these reasons, the pathology must be interpreted in the context of the peculiarities of mice and the similarities and differences between humans and mice. Otherwise, the interpretation can be misguided. This requires an experienced comparative pathologist. With regards to this proposal, I am uniquely qualified by my previous experience and particularly my experience with this methodology to test for toxicity, tumor growth, and tumor response to therapy. In the previous and ongoing studies, interesting, significant, and unexpected lesions have been identified. I am very excited about the proposed studies and look forward to a productive collaboration.