Despite recent advances in diagnosis and therapy, respiratory disease remains a major cause of morbidity and mortality in neonates and children. The specific etiologies for lung disease in this population are frequently unknown. The Clinical Core will serve as a resource for the individual program components by collecting and analyzing clinical samples pertaining to a variety of neonatal and adult pulmonary diseases, in which abnormalities of lung development and growth, surfactant function and metabolism, and/or remodeling after injury are suspected. The overall goal of these studies will be to characterize and identify mechanisms that cause idiopathic lung disease and developmental abnormalities. Dr. Lawrence Nogee, Johns Hopkins University School of Medicine, will perform genetic analyses for mutations in lung-specific genes, such as the surfactant proteins, the GM-CSF Bc receptor, and TTF-1. Analysis for protein expression in frozen lung tissue, BALF, or tracheal aspirates will be performed by Dr. Jeffrey Whitsett; phospholipid analysis and surfactant function by Dr. Machiko Ikegami; and immunohistochemistry by Dr. Susan Wert, in conjunction with the Morphology Core. Analytical results will be entered into a computerized database for future reference and data analysis. As the Clinical Core identifies novel mutations in lung-specific genes, they will be tested for their capacity to cause lung disease, to disrupt surfactant function and/or metabolism, or to induce pulmonary malformations. Testing of selected mutations in vitro or in transgenic mouse models will be done in the context of each of the individual program components. These studies should enhance our understanding, of pulmonary development and pediatric lung disease, leading to the development of new treatment strategies for respiratory disorders.
