Grant: Project Grant

The aryl hydrocarbon receptor (AhR) is a protein found in almost all of the cells in our body. Much of what is known about the AhR centers on its ability to cause toxic effects of man-made environmental chemicals called dioxins. There is growing evidence that the AhR is required for the maintenance of health, and controls normal processes that occur in the body such including organ development and immune function. Dysregulation of AhR expression and activity is also associated with a variety of disease states, particularly those at organs such as the lungs. The lungs are particularly vulnerable to inhaled compounds such as cigarette smoke, which is still the leading cause of preventable death. Our studies are aimed at understanding how the AhR stops inflammation in the lungs after repeated exposure to cigarette smoke. Cigarette smoking is also the most important risk factor for chronic obstructive pulmonary disease (COPD), a disease that makes breathing difficult. Even non-smokers can develop COPD. Although current therapies can make breathing easier, there is no cure for COPD. However, we have already shown that the AhR is import in protecting the lungs against cigarette smoke, but we still do not understand how the AhR is working. Therefore, we will now assess signaling paradigms through which the AhR is working. We will also test the therapeutic potential of AhR against the deleterious effects of smoke by using a protein that is produced in the body. Even though quitting smoking reduces the likelihood of developing COPD, damage associated with long-term tobacco may still progress to disease. This research may lead to new approaches that would block some of the health consequences associated with inflammatory lung diseases such as COPD.