Dr Jennifer Dickens

The early pathogenic events in pulmonary fibrosis are poorly understood. Repeated injury to the alveolar epithelium alters the behaviour of alveolar type 2 (AT2) cells, rendering them unable to repopulate denuded epithelium and altering their phenotype and secretomes. This triggers a cascade of downstream pathogenic events that results in lung parenchyma remodelling and progressive fibrosis. Modelling these early pathogenic events is complex, both because of the challenges of alveolar epithelial culture in vitro and because disease is usually already well established at presentation.

Monogenic inherited forms of pulmonary fibrosis can be caused by defects in surfactant biology or in telomere maintenance; studying how these pathogenic variants causes disease gives us an opportunity to understand the cellular dysfunction caused by a known trigger.

Our work focuses on understanding the mechanisms by which these pathogenic protein variants cause AT2 dysfunction and how we may be able to target dysfunctional pathways therapeutically. Using alveolar organoid and complex co-culture models, we wish to unpick how surfactant-related proteins are handled by AT2 in health and in disease and how they mediate their pathogenic effects, both in AT2 cells and in the wider context of the alveolar niche. We will then use these findings to undertake high throughput drug screens. We are also interested in the concept of accelerated AT2 cell ageing; how senescence evolves, and how senescent cells influence the alveolar niche to drive the evolution of pulmonary fibrosis.