Grant: Master's Award: Canada Graduate Scholarships

Bronchopulmonary dysplasia (BPD) is a disease of impaired development in the blood vessels and airways of the lungs of infants. The disease generally affects premature infants and is a leading cause of both neonatal mortality and morbidity into adulthood for this population. Work in our lab has shown that a type of immune cell, called the natural killer (NK) cell, regulates blood vessel development in the lungs through the actions of an immunosuppressive protein called transforming growth factor-beta (TGF-ß). Genetically modified mice with NK cells that are insensitive to TGF-ß exhibit a BPD-like impairment in lung development within the first week of life. My work aims to fully characterize the cells and molecules underpinning this developmental impairment. First, we will examine gene expression in single cells within the developing mouse lung to track lung development in our genetically modified mice over the first week of life. We will identify how interactions of NK cells with specific cell types in the lung drive changes in blood vessel structure. Second, we will assess lung function and structure in adult mice to test whether the lungs of these mice can repair themselves over time. Finally, we will stress adult mice by exposing them to hypoxia (10% O2) and assess how this genetic modification impacts the restructuring of the lung blood vessels in response to this stress. By characterizing the process by which mice with TGF-ß-insensitive NK cells develop BPD, we hope to understand how these cells contribute to lung development and vascular maintenance and use this information to develop new disease biomarkers and treatments.