Investigation into the impact of mast cell activation on the vasculature during chronic lung diseases

Chronic lung diseases such as asthma and COPD are a major health problem in the UK with an estimated 1/5 people impacted by one form of lung disease and this number is predicted to increase in the next decade. One underestimated impact of respiratory disease is the effect of chronic inflammation on the crucial network of blood vessels in the lungs. During my previous projects and fellowship, I discovered that mast cells (MCs), a type of immune cell, play a vital role during vascular inflammation and can modulate function of pericytes, the structural components of the vascular wall. The importance of this interaction in the lungs, where MCs and pericytes are abundant, remains to be investigated. My proposed project, combining mouse models, human samples, spatial transcriptomics, and 3D analysis of blood vessels will shed new light on this important question. I will investigate how the hyperactivation of MCs leads to pericyte loss, and how this impacts lung vascular function. Furthermore, this transdisciplinary proposal will identify MC-derived factors such as proteases as potential therapeutic targets. In summary, my project will develop strategies to prevent pericyte dysfunction and further prevent respiratory and vascular disorders during chronic lung diseases.