Genetic regulation of neonatal pulmonary surfactant deficiency has been suggested by studies of gender, genetic linkage, recurrent familial cases, gene knockout models in mice and by racial disparity in risk of neonatal respiratory distress syndrome. Successful fetal-neonatal pulmonary transition requires production of the pulmonary surfactant, a phospholipid-protein film that lines alveoli and maintains alveolar patency at end expiration. Our goals are to understand the genetic mechanisms that disrupt pulmonary surfactant metabolism and cause neonatal respiratory distress syndrome as well as to understand the implications of these genetic mechanisms on the development of interstitial lung disease and pulmonary fibrosis.
To discover genomic variants associated with neonatal respiratory distress syndrome and childhood interstitial lung diseases, we use candidate gene-focused (multiplexed direct genomic selection) and unbiased (exome sequencing and whole genome sequencing) next generation sequencing strategies and advanced computational quality, coverage and filtering methods. To predict function of discovered variants, we use a suite of algorithms that incorporate evolutionary conservation and known regulatory motifs. Finally, we use human cell culture model systems to test biologic function of discovered variants.