The focus of my research is investigation of pathobiology of cystic fibrosis (CF) in the gastrointestinal (GI) system. CF is caused by mutations in the CFTR gene. CFTR is a cAMP-regulated chloride channel expressed in many epithelial cells. In the absence of functional CFTR, exocrine secretions are poorly-hydrated and viscous mucus covers affected epithelial surfaces. In the GI system accumulation of mucus can lead to obstruction of the lumen. Accumulated mucus also provides a niche for abnormal bacterial colonization and overgrowth. GI motility has been reported to be impaired in about half of CF patients, and this may contribute to bacterial overgrowth. These effects of CF interfere with proper nutrition, are detrimental to overall health, and lower the quality of life in CF patients. Using the Cftr knockout mouse (Cftr tm1UNC) model of CF we are investigating the inter-related roles of excessive mucus, abnormal bacterial growth, and impaired motility in the pathophysiology of CF in the intestine. The long term goal is to provide new therapeutic interventions to improve intestinal function in CF. This work includes in vivo and in vitro studies; morphological and immunocytochemical techniques; and measurement of mRNA and protein levels for various inflammatory markers and signaling molecules.