Mutations in VE-PTP: Identification of a Novel Cause of Venous Malformations in 3D-Matrices
Mutations in the vascular endothelial protein tyrosine phosphatase (VE-PTP), one of the most important interaction partners of angiopoietin receptor Tie-2, were recently discovered in eight patients suffering from venous malformations. The aim of this project is to validate the prelimi- nary results of two candidate mutations, acquired from COS7 cell experiments – an impaired ability to dephosphorylate Tie-2. Confirming these results in VE-PTP re-transfected primary endothelial cells will depict the first milestone and provide essential evidence to allow a subsequent set of main experiments: A microfluidics-based experiment in three-dimensional hydrogels is planned to reveal potential abnormal vessel formation as it occurs in VM patients.
The described project is targeted at utilizing patient derived mutations and a set of in vitro experiments designed for mimicking true physiological in vivo conditions, thus, reducing the number of further animal experiments. Only in case of positive results, the experiment conducted by Boscolo et al. will be repeated to validate the data in an in vivo system in future experiments.