Jak2 V617F myeloproliferative neoplasms.
The JAK2 V617F mutation is present in 90% and 50% of patients with Polycythaemia Rubra Vera and Essential Thrombocythaemia respectively. The clinical hallmark of these conditions is an increased red cell/platelet count and increased risk of cardiovascular events. Using knock-in mouse models of heterozygous and homozygous Jak2V617F disease produced by Prof Anthony Green’s group, we analyse how the mutant JAK2 leads to increase platelet production and alters platelet function through a range of in vivo and cell biology assays.
Nbeal-/- Gray Platelet Syndrome
The lack of NBEAL2 protein leads to Gray Platelet Syndrome in humans. We are using an Nbeal2-/- mouse model generated by the Sanger Institute to study granule formation and megakaryocyte maturation in the context of this disease. Other mouse models of megakaryocyte/platelet disorders are currently under investigations stemming from the Sanger Institute Mouse Genetics Project or from targeting genes identified in studies of pedigrees with inherited platelet disorders (https://bridgestudy.medschl.cam.ac.uk/).
Preclinical studies of in vitro derived blood cells
Immunodeficient mice constitute an ideal organism to study human cell function in vivo. Studies of blood cells derived in the laboratory in these mice provide invaluable data of safety and efficacy prior to administration to humans.
Key people: Dr Jose Guerrero (post-doc), Cavan Bennett (research assistant), Dr Thomas Moreau (post-doc), Dr. Cedric Ghevaert.
Collaborators: Dr Dave Adams (WTSI), Prof Anthony Green (Department of Haematology), Professor Willem Ouwehand (Department of Haematology), Dr Marloes Tijssen (Department of Haematology).