PhD Programme for Clinicians at the University of Cambridge: 'Developmental studies of murine and human lung development towards differentiation of human induced pluripotent stem cell to lung epithelial progenitors'. (360G-Wellcome-100677_Z_12_A)

Respiratory diseases are associated with a high and increasing global incidence of mortality and morbidity which is related to the inability to meet the demands for lung transplantation. Human induced pluripotent stem cells (hiPSCs) might enable the differentiation of patient-specific iPSCs into any relevant cell type to be used for disease modelling and drug screening and could also bring us a step closer to cell-based therapies, including personalised organogenesis. For disease modelling, generating disease-specific lung epithelial cells from hiPSCs is particularly important because murine models often do not phenocopy human lung disease. Published differentiation protocols are based on the assumption that to produce fully mature epithelial cells, progression through a progenitor stage is necessary. The inability to efficiently produce fully mature epithelial cells might be due to an inability to produce bona fide lung progenitors. I aim to ascertain optimal conditions for the generation of human lung progenitors from hiPSCs using the naïve pluripotent stem cell platform of the Smith laboratory. To achieve this, I will also characterise both early human and murine lung development. Intensive study of those should provide me with a road map to recapitulate the milestones of early development in order to efficiently drive iPSCs toward mature lung epithelial cells.