Lung Development and Regeneration
Epithelial cells in the lung form a highly organized tubular network exposed to air, pollutants and pathogens to facilitate breathing. To elucidate the genetic blueprint of airway cell differentiation and morphogenesis we use the powerful genetic tools available in Drosophila airways combined with live imaging and single cell transcriptomics in the mouse lung. A major aim is to identify the cellular heterogeneity and plasticity in the lung epithelium during homeostasis and upon injury or infection. Mechanistic studies in flies, showed that the selection of differentiated and multipotent stem cells in the airway tree relies on a sensitive balance of Wingless, Hedgehog and RTK signaling. Our single cell mRNA sequencing of lung epithelial cells and in situ sequencing experiments in mice revealed a large variety of airway cells and their candidate cell fate regulators. We now use mouse genetics, live imaging of mouse lung slices and cultures of human bronchial cells to probe the regulatory circuits that select and maintain distinct populations of stem- and differentiated cells.
Lung diseases, including cancer are among the leading causes of death worldwide with still unmet treatment challenges. Using high-resolution, single cell analysis technologies we hope to understand the cellular and molecular programs leading to normal lung development and to discover how these programs become misdirected to cause terminal lung diseases.