Project 454464

Interstitial lung diseases (ILDs) are serious conditions that result in scarring of the lungs, breathing difficulties, and often a severely shortened lifespan. Recent evidence suggests that air pollution may contribute to the development and progression of ILD, but we do not understand how pollutants exert these effects. This project will investigate how a patient's genetics influence their responses to air pollution, how pollution alters which genes are turned on or off in the lungs, how the small airways of the lungs are impacted, and how these changes impact disease progression. We will start by evaluating how specific genes known to be associated with ILD impact how an individual will respond to air pollution exposure. Next, we will look at molecular patterns on DNA that regulate which genes are turned on or off (i.e. epigenetics) and the amount of a gene that is being used to make protein products (i.e. their gene expression levels) that are found in the blood and lungs of patients with ILD. Through this process, we aim to identify molecular signatures that can tell us about a patient's pollution exposures and their risk of ILD progression. Lastly, we will perform micro-scale imaging of lung tissues donated from patients with ILD to better understand how the small airways and alveoli of the lungs change in response to pollution exposure and as the disease progresses. This research will provide us with a more thorough understanding of the impact of air pollution on the lungs on a molecular and structural level, allowing us to learn how to minimize future damage and progressive scarring. In studying which genes are turned on and off in the lungs in response to environmental exposures, we may also identify new pathways for the development of medications to minimize or reverse lung scarring. This research will inform environmental health policies aimed at protecting vulnerable populations, including patients with ILD and other chronic lung diseases.