Our laboratory works primarily on a protein called endoglin that we discovered orginally on chidhood pre-B leukemic cells. Endoglin is however expressed primarily on vascular endothelium.
Patients have frequent and severe nosebleeds due to telangiectases.
We showed through endoglin mutation analysis and expression studies of patient material, that endothelial cells of HHT patients express a single copy of the gene as mutant proteins are retained and degraded intracellularly. This implies a haploinsufficiency model for this disorder. We have now generated an animal model of HHT by engineering mice expressing a single copy of the gene. However not all strains of mice develop disease manifestations suggesting that additional genes are needed for the generation of the complex phenotype characterized by AVMs. It acts on just about every subset of immune cells and is a very potent immunosuppressive agent.