Grant: Environments, Genes and Chronic Disease - LOI

Over past decades, the adverse effects of air pollution on human health have been investigated through independent efforts of epidemiology, toxicology and controlled human exposure models. Recently, genetic information has increased our understanding. However, there is so much genetic data, and it is so complex, that it is difficult to understand how best to use it to help people in the 'real world', especially when genetics and the environment interact with each other (making things even more complicated). We are bringing together a unique team of 10 individual researchers with varied backgrounds to try and harness the full potential of this information and leverage our findings to develop strategies to improve health. Our research skills intersect uniquely upon the following assertion: understanding the relationship between genetic variability, airborne exposures, and epigenetic changes will offer and opportunity for risk modification by distinct interventions. We propose a set of studies to characterize how genes and exposure to inhalants such as air pollution and allergens interact to affect asthma. We think that this can lead to reduced harm but we lack clear evidence and plausibility that the path from genome-level data to reducing the toxicity of harmful inhalants can be realized. Our plan is to use complementary human and animal exposure models to test the effectiveness of agents that modify the relationship between gene and exposure, to provide a rich set of epigenetic data from blood and lung tissue. Then we will use computer models to illuminate discoveries not previously possible. Finally, we will ask how and when this knowledge is desirable to end-users so that it can be transferred in a meaningful way. We focus on air pollution and asthma given our clinical expertise and the worldwide prevalence of this condition, but will aim to construct a model that extends to other exposures and chronic disease conditions.