Expression Profiling in Canine Models of Human Disease

DESCRIPTION (provided by applicant): Large-scale measurement of gene expression has the potential to provide a wealth of information regarding the mechanisms of adaptive and maladaptive responses to disease. However, the ability to study temporal changes in gene expression under carefully controlled conditions during disease progression is severely limited when working with human subjects. We have assembled a group of collaborating investigators who have extensive experience in the study of the pathobiology of a number of diseases of the heart, lungs, kidneys and vasculature in humans and animal models. Most importantly, all share a long-standing interest in the use of canine models of human disease to study the natural history of disease and the effects of therapeutic interventions using serial tissue sampling; as a consequence there is a wealth of biological material that will serve as targets for expression profiling experiments. In an effort to better understand the molecular mechanisms of adaptive and maladaptive responses to cardiovascular, pulmonary, vascular and renal disorders we propose to profile global changes in gene expression in canine models of human disease. The aims of this proposal are: 1. Generate and validate canine cDNA arrays for expression profiling; 2. Provide computational and informatics support for the research activities of the proposed array facility including the implementation and maintenance of databases supporting tissue-specific and regional analyses of gene expression data and the development of algorithms for data analyses that support the scientific aims of the proposal; 3. To profile gene expression in the dog including the characterization of regional variations in gene expression in the normal canine heart and spatiotemporal changes that occur during the development of models of cardiovascular, pulmonary and renal disease. The data and reagents generated in performance of the aims of this proposal will constitute an important and generally available resource to investigators not only at our institution but worldwide. We will make canine-specific sequence information easily accessible to investigators over the World Wide Web. As expression profile data is generated, it will be incorporated into a web-based database of canine gene expression profiles.