Grant: Operating Grant

The lung disease of idiopathic pulmonary fibrosis could be more effectively treated if the altered genes which contribute to its development were known. Idiopathic pulmonary fibrosis is a genetically complex disease which can result from known (environmental, therapeutic) exposures and involves a pathology of excessive scar formation in the lung which can result in impaired lung function and, ultimately, respiratory failure. This devastating disease has an estimated annual incidence of 1 case per 10000 members of general population and an associated mortality of 50-70% at 5 years post diagnosis. Genetic differences among people likely contribute to who develops this response and who does not. In the proposed research we will study animal models which present the same lung disease as patients suffer, to identify specific inflammatory responses and genes which predispose to the development of these effects. Such genes are more easily detected in animal models (than in the clinic) as breeding permits the needed number of animals to be created. The proposed investigations will use the latest advances and approaches of genomics research, related to the Human Genome project, to uncover specific lung response genes for later testing in a patient population. It is anticipated that the mouse studies will provide evidence for variation within specific genes leading to fibrosis, and that these genes could then be investigated in the clinic. The elucidation of genetic differences leading to fibrosis will also provide potential targets for therapeutic intervention. New targets are needed, as there are presently no approved drugs for pulmonary fibrosis.