Despite recent advances, inflammatory disease remains a significant global health problem causing extensive pain and comorbidity in patients. Recruitment of inflammatory leukocytes to tissues is key in establishing and propagating inflammatory disease by producing local damage, leading to an inflammatory loop. Chemokines provide the key signals enabling circulating leukocytes to leave blood vessels and enter tissues. Despite extensive research chemokines (and their receptors) have not been successfully therapeutically targeted, in this context, and new approaches are needed.

The glycocalyx is a thick, hydrated and adhesion resistant cell-matrix barrier that lines blood vessels, largely composed of proteoglycans. This structure is a critical, but understudied, regulator of leukocyte:endothelial interaction events and thus mediates leukocyte recruitment during inflammation and disease.

Currently we lack understanding of how emigration of leukocytes is molecularly orchestrated in the presence of the thick glycocalyx layer and I hypothesise a key role for chemokines in this process.

My lab is focused on using biochemistry, biophysics and in vivo biology to study chemokines, the glycocalyx and inflammatory disease.  Specifically, how chemokines enable leukocyte crossing of the adhesion-resistant endothelial glycocalyx barrier and how the glycocalyx barrier regulates leukocyte migration/endothelial permeability; processes that are critical to a wide range of diseases from inflammatory pathologies to cancer. This approach is enabled by the unique facilities on offer within the Wellcome centre for cell-matrix research and the University of Manchester.