Our group investigates the genetic and biological determinants of diseases that are influenced by the environment. Our previous research has focused on the lungs and the immune system, trying to understand why environmental agents cause lung disease and infections in some people but not others. We have discovered that a variant of the gene TLR4 makes some people more susceptible to adverse effects of bacteria, that epigenetic mechanisms may be important in the development of asthma, and that a variant in a mucus producing gene (MUC5B) in the lung markedly enhances the risk of developing pulmonary fibrosis. More recently, we have focused on epigenetic mechanisms that are contributing to the development of allergic airway disease, pulmonary fibrosis, and innate immune responsiveness. Human and animal models are used to pursue these studies. Our research in these areas has the potential to develop biomarkers for early identification of susceptible individuals, lead to novel concepts about the prevention and pathogenesis of these diseases, and to transform therapy in pulmonary fibrosis, microbial infections, sepsis, and asthma.