Genetics Seminar Series: Uncovering principles of stem cell-mediated repair and regeneration in the lung

My research aims to understand the molecular and cellular basis of tissue injury and regeneration in the mammalian lung. In my recent work, I have established longitudinal timelapse imaging of intact lung tissue in vivo and ex vivo to show that a large fraction of alveolar stem (AT2) cells become highly motile upon injury. To our surprise, we uncover direct evidence that AT2 stem cells migrate between alveoli – ie., between individual functional units of the lung. We use unbiased morphokinetic profiling to map the behavioral evolution of AT2 cells and uncover the emergence of distinct motile phenotypes, revealing an unappreciated level of behavioral heterogeneity during migration of stem cells. Inhibition of AT2 cell motility leads to impaired regeneration of AT1 and AT2 cells in vivo following two different modes of lung injury. This work reveals stem cell motility and migration between functional units as an important mechanism of tissue regeneration. New approaches to further interrogate dynamic stem cell behaviors in the alveolar niche together with genetic mouse models, multiomics and human tissues will help uncover new principles of regeneration and repair.