Department of Physiology,
University of South Alabama
College of Medicine
Mobile, AL 36688
B.S., North Carolina State University
M.S., University of Kentucky
Ph.D., University of North Carolina
Control of the volume of surface liquid which covers the pulmonary epithelium is critical for normal mucociliary clearance and for efficient gas exchange. The role that active transepithelial ion transport plays as a driving force for liquid movement across the pulmonary airways is currently under study. We measure the bioelectric properties of isolated bronchi and bronchioles as correlates of active ion transport activity. We then use selective transport inhibitors and stimulators to determine which transport pathways are present and how these processes are regulated. In persons afflicted with cystic fibrosis (CF), a molecular defect in an epithelial chloride channel is present that leads to a myriad of pathological problems, the most critical of which involves secretion of thickened, dehydrated mucus into the airways. A major focus of our research is to determine how such defects in chloride ion transport are mechanistically related to the development of the symptoms observed in cystic fibrosis patients. Our findings suggest that fluid secretion from the submucosal glands of the trachea and bronchial airways is disrupted in CF, leading to the production of a highly concentrated mucus that is poorly cleared from the airways by cough or by mucociliary transport. We use techniques for measuring liquid secretion, mucociliary transport, and ciliary beat frequency to determine the importance of interactions between periciliary fluid, mucus, and cilia at the airway surface for maintaining normal ciliary clearance. We also model important aspects of CF lung disease in porcine isolated lungs by perfusing the vasculature with selective inhibitors of anion secretion. We are now expanding our studies by exploring new ways to model CF lung disease including use of in vitro (siRNA) and in vivo (screening non-humam animal populations for mutant CFTR) approaches. We believe that our findings are of great importance for understanding the underlying cause of CF lung disease and for development of effective treatments.
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