Complementary approaches support the major research interests of my laboratory: Gene Transfer to the Lungs: My initial interest in gene therapy has resulted in a basic focus on adenovirus and adeno-associated virus receptors biology. CAR is a transmembrane protein that plays a dual role as a homotypic junctional adhesion protein and as a receptor for adenovirus. AAV5 is very promising as a vector for gene therapy. We showed that the receptors for this virus are localized to the apical surface of airway epithelia. Pathogenesis of Cystic Fibrosis: Abnormal salt absorption in CF: A major effort in my laboratory is to understand and resolve the differences between in vitro, murine, and human studies of airway epithelia ion transport. To explain why lack of an apical chloride channel results in altered salt and fluid homeostasis. Antimicrobial Properties of ASL: Xylitol, a 5-carbon sugar, can enhance bacterial killing of the airway surface liquid by enhancing the activity innate salt-sensitive antimicrobials. My laboratory has obtained an IND from the FDA to study the safety, pharmacokinetics and efficacy of aerosolized xylitol. A novel innate immunity against bacteria 'Paraoxonases': A major effort in my laboratory is to investigate the effect of paraoxonases on P. aeruginosa virulence and biofilm formation. We hypothesize that PONs, by interfering with quorum-sensing, is an important component of the innate immune system. We are testing the effect of targeted deletion of PONs on the susceptibility of mice to P. aeruginosa airway colonization, pneumonia and sepsis.