Grant: Operating Grant

Congenital Diaphragmatic Hernia (CDH) is a developmental disorder occurring in approximately 1 in 2500 live births (similar to the occurrence rate of Cystic Fibrosis). The primary characterization of CDH is that the diaphragm muscle fails to form properly during pregnancy. Normally, the diaphragm develops to form a continuous sheet that completely separates the space where the lungs develop. However, in the instance of CDH, a significant proportion of the diaphragm is absent. Consequently, the developing abdominal organs can invade the chest cavity, occupying space normally reserved to accommodate the growing lungs. As a result, newborns with CDH suffer from a combination of very small lungs and serious heart problems (approximately 50% die soon after birth and survivors often have life-long health concerns). Our laboratory uses a variety of animal models that very much mimic CDH in infants. Using these models, we will continue with our discoveries of why there is a hole in the diaphragm muscle, what stage of pregnancy the defect first occurs, what genes may be involved and the potential role of an abnormality of Vitamin A regulation in the embryo. We have made significant progress during past several years and have some novel targeted studies designed to advance our understanding of this serious birth defect.