Targeting remodelling of lung stem and niche cells: lessons from regeneration to disease

Most tissues possess the remarkable capacity to self-regenerate after injury. In the lung, a regenerative response involves recreation of alveolar air-filled sacs and restoration of tissue integrity. However, with age and in chronic disease, the regenerative response often switches to lead to fibrotic scarring, compromising lung function and leading to mortality. Therefore, a deeper understanding of the process of lung regeneration and why it becomes dysregulated following chronic damage is urgently needed. We will define the changes of stem cells and their neighbouring cells which are engaged in regeneration and establishment of disease following injury. This will allow us to identify candidate targets which we can validate in preclinical 3D human lung disease models that we have developed. Our proposed study will provide fundamental new insights into the ways regenerative programmes are regulated as well as the development of therapeutic interventions to treat lung diseases.