Molecular regulation of vascular permeability
Description: Endothelial cells constitute a barrier that regulates the exchange of large molecules and cells between blood and tissues. In response to vascular endothelial growth factor (VEGF), and inflammatory cytokines, vascular permeability increases transiently, allowing extravasation of blood constituents. In diseases, the barrier may deteriorate chronically, resulting in elevated interstitial fluid pressure, poor circulation, reduced therapeutic access and disease progression. We will explore mechanisms for how vascular permeability is regulated in healthy vessels compared to tumor vessels, in particular through Src family kinases. Moreover, permeability regulation during ageing will be examined, and we will study the effects of a small molecular weight inhibitor on barrier stabilization. The goals are to delineate how the vascular barrier contributes to tissue homeostasis and how its breakdown accelerates ageing and disease. The research will be carried out by the experienced group of the applicant, using in vivo methodology on mice, and validation using human tissues. Experimental tools include RNAseq, in situ RNA hybridization, high resolution imaging and analyses on mice challenged by different disease models such as cancer and retinopathy. In particular, the aspect of ageing is a longterm project. This project will provide new basic molecular understanding of complex, dynamic control of the vascular barrier and provide tools to suppress pathological vascular leakage.
Funder: Vetenskapsrådet
Amount: SEK 4,050,000
Funding type: research
Funder scheme: Project grant
Start date: 2026-01-01
End date: 2028-12-31
Investigator: Lena Claesson-Welsh
Institution: Uppsala University
Funded outputs count: 1
Funder award ID: 2025-02853
OpenAlex ID: G6019529626