Developmental Origins of Cardiopulmonary Disease

The O'Reilly lab consists of an interactive group of senior scientists and physicians, graduate students, technicians, and summer undergraduate scholars interested in understanding how an abnormal oxygen environment at birth affects cardiopulmonary health later in life.

It is widely accepted that gene-environment interactions during critical stages of fetal and postnatal development can profoundly shape health later in life. One of the most profound environmental factors that the developing lung will ever experience is oxygen as it transitions at birth from a fetal to air environment. While the term lung is developmentally prepared for oxygen, the preterm lung is exposed too soon and often to excess amounts used to maintain appropriate oxygen saturations. This early exposure to excess oxygen can disrupt lung development and the host response to respiratory viral infections. It may also cause pulmonary hypertension and heart failure in young adults. Hence, there is an urgent need to understand how an abnormal oxygen environment at birth disrupts postnatal development of the lung and heart.

Using human datasets and the mouse as a model system, we are studying how high levels of oxygen at birth alter growth and differentiation of epithelial progenitor cells required for proper lung development and regeneration. We then investigate how these progenitor cells and oxygen-induced DNA damage signaling influences how the lung responds to respiratory viral infections. Recognizing the growing concern that young adults born preterm are at risk for developing cardiovascular disease, we also study how oxygen at birth promotes pulmonary hypertension and causes heart failure later in life. Our research has produced important and novel insights into disease processes that we hope will lead to new biomarkers needed to predict risk and guide development of novel therapies designed to improve health of people who were born preterm.