Research

Asthma is caused by abnormal immune responses to allergens such as pollens and dust mites. However, asthma is also related to the genetic makeup of an individual, so that parents who have asthma are more likely to have children who also have asthma. The genes in our DNA encode proteins that have very diverse functions. For example, some proteins are receptors that direct cellular responses to external stimuli. Other proteins function as enzymes, which are able to modify other molecules. The aim of our research is to understand how genetic variation changes the function of proteins and enhances the risk of developing asthma. The IL-4R? receptor is found on inflammatory cells. However, asthmatics are more likely to have a form of IL-4R? that stimulates an exaggerated immune response. We have shown that changes in this receptor intensifies inflammation in the allergic lung and the way in which allergens stimulate immune cells to release factors that damage the airways. Compared to non-asthmatics, cells lining the lung in asthmatics are more susceptible to damage by toxins such as those found in air pollutants and cigarette smoke. Glutathione transferase Pi (GSTP) is an enzyme that inactivates toxic metabolites and a genetic variant of GSTP is known to enhance the risk of developing asthma. Our studies have shown that GSTP plays a critical role in inhibiting the development of allergic inflammation and abnormal respiratory function in the lung. Collectively, our studies are constructing an integrated picture of how changes in our genetic makeup enhance the likelihood of asthma. In the future, this information will enable better targeting of medications that preventor alleviate the symptoms of asthma.