Projects
Genetic Contributions to Newborn RDS
We are investigating the association of genetic variation in several genes where mutations cause lethal surfactant deficiency (SFTPB, SFTPC, and ABCA3), as well as other genes involved in pulmonary surfactant synthesis, transport, and catabolism, the unfolded protein response, and fluid homeostasis, to RDS.
Genetic Epidemiology of Surfactant Dysfunction Mutations
For subjects who are referred to us for unexplained or otherwise unusual symptoms of respiratory distress, we initially screen for common mutations in SFTPB and ABCA3. Additionally, we resequence these and/or SFTPC to find new mutations that may predict or correlate with the subject’s clinical phenotype.
Measurement of Surfactant Phospholipid and Protein Turnover Using Stable Isotopes
To determine if surfactant metabolism is disrupted in premature newborns with evolving chronic lung disease, we utilize naturally occurring, stable, non-radioactive isotope labeled metabolic precursors of phospholipid synthesis to compare in vivo surfactant metabolism in infants with lethal and non-lethal RDS. The protocol concurrently tracks three aspects of surfactant metabolism: surfactant pool size, surfactant production, and surfactant catabolism. The application of labeled metabolic precursors of surfactant phospholipid synthesis provides a unique and powerful approach to evaluate disruption of surfactant metabolism and will lead to specific and clinically useful interventions to restore pulmonary function.
Role of Epidermal Growth Factor in the Development of Necrotizing Enterocolitis
Along with several other labs, we are involved in the use of a multi-faceted approach including gene sequencing, stable isotope infusions, and analysis of stool specimens to develop genetic, metabolic, and inflammatory signatures in premature infants at risk for NEC.