This application proposes to continue multidisciplinary studies of development, control and disorders of the pulmonary parenchyma. The objectives of the proposal are to examine some of the mechanisms involved in the formation and stabilization of the pulmonary parenchyma during development and post-natal life, and in states of health and disease. By stabilization we mean the integrated physiochemical and biological processes that develop and maintain alveolar architecture in an optimal state for pulmonary gas exchange. As in our past studies we emphasize investigations of alveolar epithelial development, functions of the lung surfactant system, and alveolar disease processes leading to infection and inflammation. The broad goals of the three inter-related projects proposed are: Project 1: Structure and function of surfactant proteins. To study the relationship between the structure of the surfactant proteins, specifically SP-D, and their functions in regulating the immune milieu of the alveolus. Project 2: Expression and role of CEACAM6 in the alveolus. To investigate the role of carcinoembryonic antigen-6 in alveolar innate immune defense, surfactant function, and epithelial response to acute lung injury. Project 3: Alveolar epithelial cell fates: mapping and regulation. To study alveolar epithelial cell lineages during development and regeneration and to elucidate novel regulatory molecules important to the process of alveolar epithelial differentiation. The overall purpose of these studies is to deepen our understanding of the processes underlying lung parenchymal stability and to contribute to new concepts and treatments for lung diseases associated with disorders of alveolar stability, growth, maturation, and repair after injury.

Public Health Relevance

Normal development and function of the alveolar region of the lung is critical to the exchange of oxygen and carbon dioxide, and therefore human health. Our proposal addresses fundamental questions of how the lung is protected from infection and inflammation and how the cellular lining of the lung is generated during development. The findings will contribute to a better understanding of lung injury and repair and potentially lead to new approaches to treatment and prevention.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Special Emphasis Panel (ZHL1-PPG-S (05))
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Lin, Sara
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Barrette, Anne Marie; Roberts, Jessica K; Chapin, Cheryl et al. (2016) Antiinflammatory Effects of Budesonide in Human Fetal Lung. Am J Respir Cell Mol Biol 55:623-632
Danhaive, Olivier; Chapin, Cheryl; Horneman, Hart et al. (2015) Surface film formation in vitro by infant and therapeutic surfactants: role of surfactant protein B. Pediatr Res 77:340-6
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