The relationship between genetic susceptibility and environmental exposure in the development of disease has been hypothesized for many years. It has also been hypothesized that inherited differences in DNA sequence contribute to phenotypic variation, influencing an individual's risk of disease and response to the environment. The investigators propose to design novel techniques to investigate the role of single nucleotide polymorphisms (SNPs) in the association of asbestos exposure and the development of asbestos-related diseases. The hypothesis is that by bringing together an interdisciplinary team and outside experts, new epidemiological techniques can be created to more efficiently and reliably develop a novel study design. The mechanism to achieve this goal is to create opportunities for multidisciplinary interaction, as well as interaction with the study community. The scientific hypothesis is that SNPs in the genes involved in the asbestos-response pathway may be responsible for conferring sensitive or resistant phenotypes to asbestos-induced disease development in humans. To test the hypotheses, and to achieve the goals of the proposal, the investigators will: (1) educate the team members in each other's disciplines, (2) develop new molecular epidemiology techniques to investigate the connection between environmental exposure and susceptibility to exposure-induced diseases, (3) develop mechanisms for communication between study populations and investigators, (4) use pilot projects to develop preliminary data, and (5) prepare and submit a RO1 grant proposal using the novel methods developed by the team as validated by the preliminary data obtained from the pilot projects. Through these mechanisms, the investigators will establish the tools that will enable them to perform innovative investigations of the individual risks of disease development after asbestos exposure. The goal of this proposal is to prepare a RO1 application to address this question, having in place a strong team that has developed the best investigative methods possible. In the process, they will determine the polymorphisms important for susceptibility and/or resistance in genes involved in the asbestos-response pathway, for the ultimate purpose of improving the understanding of the mechanisms of these lung diseases.
| Marchand, Lucas S; St-Hilaire, Sophie; Putnam, Elizabeth A et al. (2012) Mesothelial cell and anti-nuclear autoantibodies associated with pleural abnormalities in an asbestos exposed population of Libby MT. Toxicol Lett 208:168-73 |
| Pershouse, Mark A; Smartt, Aubrey M; Schwanke, Corbin et al. (2009) Differences in gene expression profiles from asbestos-treated SPARC-null and wild-type mouse lungs. Genomics 94:101-9 |
| Pfau, Jean C; Sentissi, Jami J; Weller, Greg et al. (2005) Assessment of autoimmune responses associated with asbestos exposure in Libby, Montana, USA. Environ Health Perspect 113:25-30 |
