The laboratory is also attempting to develop gene transfer as a potential treatment for CF and other genetic diseases. Earlier work from Dr. Welsh and his colleagues showed that CFTR is a regulated Cl - channel located in the apical membrane of airway epithelia as well as other epithelia affected by the disease. The lab uses a variety of cellular, molecular, and physiologic techniques to investigate the structure and function of CFTR and to learn how CF-associated mutations cause dysfunction. Although much has been learned in the past few years about the cellular and molecular basis of CF, the pathogenesis of CF lung disease, the major cause of morbidity and mortality, has not been understood.
Lung disease is characterized by bacterial colonization and chronic airway infection.
The fact that patients with CF are not predisposed to infections outside the lung suggests that there must be some defect in local airway host defense mechanisms. To test this possibility the laboratory grew airway epithelia under conditions that allow them to mature into a ciliated airway epithelium. They then inoculated bacteria directly onto the air-covered surface. They found that common CF pathogens were killed when added to the apical surface of normal airway epithelia. In contrast, the bacteria multiplied on CF epithelia.