The interface of signalling and flow in regulation of vascular architecture and function in genetic disease

We study central signalling components and shear forces in the rearrangement of the heterogenous endothelial cell population into arteries, capillaries, and veins with a focus on genes causing vascular malformation in familial and sporadic human genetic disease.The overall aim is to develop, identify, and deliver drugs with high precision to manipulate blood vessel expansion, regression, and malformation to treat vascular-related diseases such as cancer, stroke, diabetes, heart failure and vascular anomalies.Analysis of our unique ScRNAseq data from malforming retinal vessels in mosaic genetic mouse models of human disease, exposes novel vessel-subtype specific genes of interest that will be validated in patient material and explored for therapeutic manipulation in mouse and fish models.

We dissect the relative impact of downstream components PI3K and AKT, under the influence of flow, on arteriovenous malformation.

We apply and develop advanced Cre-Lox/AAV genetic mouse models of human vascular disease in combination with in vivo 2P confocal live microscopy, microfluidics, in vivo phage display (AstraZeneca), scRNAseq and classical biochemistry.Project is driven by my lab with national and international collaboration over 5-years.The combinations of state-of-the-art technologies and unique data with direct relevance to human genetic disease, will drive therapies in modulation of vascular function and patterning for patients suffering from above mentioned diseases.