The EHERCC is delighted to announce the start of a collaboration between the Bateson Centre at the University of Sheffield and Dr Rubin to explore the feasibility of creating a valid EHE model using Zebra Fish.
Epithelioid haemangioendothelioma is a rare intermediate grade vascular tumour. The driving molecular abnormality found in the majority of EHE is the TAZ-CAMTA1 fusion protein. Understanding TAZ-CAMTA1 biology is key to developing novel treatment options for EHE. However, currently there are no established in vivo models for studying the effects of this fusion protein.
The zebrafish is an attractive pre-clinical model for studying human disease: 70% of its genome is shared with humans, it is small and robust, cheaper to maintain than mice, easy to breed, and the zebrafish embryos are transparent, which means that their blood vessels can be easily visualised using a low power microscope. The Zebrafish Facility at the University of Sheffield is a large specialist zebrafish centre with extensive experience in developing genetically engineered strains .
Using well-established protocols, the project will: (i) develop a zebrafish model that selectively expresses TAZ-CAMTA1 in endothelial cells; and (ii) describe the phenotype associated with this model focusing on the vascular morphology. In future studies, this model will be used to investigate TAZ-CAMTA1 biology including the effects of pharmacological inhibition of TAZ-CAMTA1 in high throughput small molecule screens.