The proposal describes a five-year training program for the development of an independent academic career in pulmonary cell biology. The principal investigator has acquired Ph.D. training in immunology as a Medical Scientist Training Program fellow at the University of Michigan, residency training in internal medicine at the University of Pittsburgh, and fellowship training in pulmonary medicine at the University of California, San Francisco. To gain expertise in pulmonary cell biology, he has organized a program consisting of laboratory-based research, courses, lectures, and meetings. Dr. Jay Nadel will mentor the principal investigator's scientific development. Dr. Nadel is the Director of the Multidisciplinary Research Training Program in Lung Disease and has trained more than one hundred pulmonary academicians and many of the present leaders in pulmonology worldwide. An expert scientific advisory committee consisting of highly regarded physician-scientists will provide research and career guidance. The educational program will include research seminars, research colloquia, attendance at national meetings, special courses (including lab management, grant writing, and ethical scientific conduct), and formal coursework in biostatistics and advanced cell biology. Because of its excellent resources and emphasis on multidisciplinary research, the Cardiovascular Research Institute provides an exceptional environment for the development of an academic career in pulmonary epithelial cell biology. Research will focus on the mechanisms that modulate epidermal growth factor receptor (EGFR) signaling in the airway epithelium to produce divergent responses such as differentiation (mucus hypersecretion) and proliferation (adenocarcinoma). Recently, Dr. Nadel's lab discovered a novel pathway (EGFR cascade) for the production of mucins. The application focuses on two proteins that may modulate EGFR signaling: the adhesion molecule, E-cadherin, and a protein of unknown function, Clara cell secretory protein (CCSP). The specific aims include: 1) examining the impact of E-cadherin-mediated cell-cell contact on EGFR signaling in airway epithelial cells; 2) determining whether CCSP promotes EGFR-mediated differentiation of airway epithelial cells; and 3) determining whether adherens junction-associated protein tyrosine phosphatase (PTPase) activity modulates EGFR activation.