Understanding the biology of bleeding disorders

Investigating the role of SLFN14 in megakaryocyte and platelet biology (Miss Rachel Stapley)

Platelets are small cells that help the blood to clot after an injury and prevent excessive bleeding. Some people inherit a disorder called thrombocytopenia, where they have a low number of platelets and abnormal bleeding. Dr Morgan has discovered that some patients with thrombocytopenia have changes in a gene called SLFN14, which means they produce a defective protein molecule. However, it is not known exactly how SLFN14 mutations cause thrombocytopenia and defects in platelet function. In this fellowship, Dr Neil Morgan is investigating how SLFN14 controls normal platelet formation and function using a mouse that has had SLFN14 selectively deleted from platelets and from the platelet’s ‘mother’ cells – called megakaryocytes. They are also genetically engineering mice to mirror the exact mutations seen in thrombocytopenia patients to see how these lead to low platelet numbers and excessive bleeding. This research will provide a greater understanding of the process of normal platelet formation as well as new insights into bleeding disorders caused by defects in SLFN14 and by other molecules. This will not only aid the development of treatments to prevent blood clots, but also could prevent the excessive lowering of platelet numbers that sometimes happens in people on anti-thrombosis treatment, reducing potentially dangerous side effects.