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Pediatrics / O'Reilly Lab / Projects

 

Research Projects

Effect of Neonatal Hyperoxia on Lung Development

Graphic of lung It is unclear why survivors of preterm birth often exhibit airway hyperresponsiveness and alveolar simplification. We are using molecular and cellular approaches in mice to understand how an aberrant oxygen environment at birth alters proper airway and alveolar epithelial development. We are also defining cumulative doses of oxygen in preterm infants that correlate with long-term changes in lung function and respiratory health.

Effect of Neonatal Hyperoxia on Host Defense

Graphic of virusPreterm birth increases the severity of respiratory viral infections in children through poorly understood mechanisms. By exposing mice to hyperoxia and infecting them with influenza A virus or respiratory syncytial virus, we are learning how early life oxygen perturbs how the lung and circulating immune cells respond to infection.

Effect of Neonatal Hyperoxia on Cardiovascular Disease

Graphic of heartThere is growing concern that people born preterm have an elevated risk for developing cardiovascular disease as young adults. We discovered an unexpected oxygen-dependent loss of pulmonary vein cardiomyocytes while searching for genes whose expression changed in lungs of adult mice exposed to neonatal hyperoxia. Since these muscle cells help pump oxygen-rich blood out of the lung, we are currently investigating how they are depleted by oxygen and how their loss contributes to cardiovascular disease.

Immune Dysfunction in Ataxia Telangiectasia Mutated Lung Disease

Graphic of DNAReactive oxygen species produced during hyperoxia damage DNA, resulting in the activation of the ataxia telangiectasia mutated (ATM) kinase that promotes survival of oxidized cells. Individuals with mutations in ATM are sensitive to oxidative stress, but frequently succumb to recurrent respiratory infections through poorly understood mechanisms. Although overt lung disease is not seen in mice lacking ATM, we discovered that they fail to develop sterilizing immunity to influenza A virus or to properly regenerate the infected airway epithelium. Current studies are designed to understand how ATM is required for development of immune memory and airway epithelial regeneration following influenza A virus infections.