HEMO-iPS

The blood-clotting disorder hemophilia A (HA) is a rare disease caused by mutations in the F8 gene, for which there is a clear need to develop novel disease models based on the relevant cell types that physiologically express F8. Patient-specific induced pluripotent stem cells (iPSC) offer unprecedented ways to model human diseases in a way that captures the patients’ genomic complexity. Specifically, our project aims are to use and optimize the current protocols for in vitro differentiation of iPSC into 1) functional hepatocytes and 2) functional endothelial cells (EC); 3) to generate HA patient-specific iPSC lines from carefully selected patients, which will be used for 4) assessing the effectiveness of drugs that promote nonsense codon readthrough for treating HA; 5) investigating the functional significance of missense mutations on F8; and 6) optimizing genetic correction of HA patient-specific iPSC. The project consortium is composed by two hospital-affiliated research institutes (VHRI and Molinette), and two higher education Universities (UPO and Paris XI University/INSERM), and will work closely with IBEC (research institute). The consortium Partners will combine specific leading expertise in clinical and molecular biology of HA, cell reprogramming, differentiation of hepatocytes and EC, and gene therapy, as well as significant knowledge of all Partners in different aspects of HA research, in order to create bona fide human disease models using the relevant cell types differentiated from patient-specific iPSC, and strengthening the transnational research cohesion.