Decoding epithelial differentiation in human airways towards lung disease treatments

The lung epithelium provides the first line of defense against inhaled pollutants and pathogens.

Epithelial cell diversity and its spatial organization are crucial for lung homeostasis and repair but they are still poorly characterized in the human lung.

Based on our human developmental lung cell atlas [1], the overall purpose of the proposed work is to describe and functionally dissect the transcriptional regulation of cell differentiation in the developing and mature human airway epithelium.

To exemplify how our basic findings can be translated into clinical outcomes we will develop methods for understanding and potentially treating congenital airway diseases.

Our results are expected to reveal epithelial intrinsic factors and communication patterns promoting healthy lung function and pathogen clearance.

Our specific aims are:To describe the cell type heterogeneity and topography of the human lung epithelium on the single cell level and to define normal developmental trajectories and their regulators.To functionally assess transcriptional regulatory networks in human lung cultures and generate synthetic enhancer elements targeting specifically bronchial epithelial cell types.To establish and characterize in vitro models of congenital lung disease and to attempt diversion of disease trajectories towards healthy epithelial homeostasis