How do genetic faults cause lymphoedema?

Functional studies on the EphB4 signalling pathway in patients with generalised lymphatic dysplasia (Miss Christina Karapouliou)

Supervised by Dr Pia Ostergaard, this PhD student is studying how genetic faults can lead to primary lymphoedema, a lifelong, often disabling condition affecting the lymphatic system. The lymphatic system is a network of vessels that carry a clear fluid called lymph from tissues through the lymph nodes, which contain immune cells to trap foreign bodies, returning the filtered fluid to the bloodstream. In people with lymphoedema, the lymphatic system cannot drain fluid properly and uncomfortable swellings develop. Often the skin overlying the swellings can become infected, which is difficult to treat. Dr Ostergaard’s research team has recently discovered faults in a gene called EPHB4, which causes a specific type of primary lymphoedema. They believe these faults affect development of the lymphatic system, but we do not yet understand how genetic faults cause the disease. In this project, the researchers will investigate these EPHB4 gene faults further in cells. The student will introduce the EPHB4 gene mutations into cells in the lab and compare them with cells with the healthy gene to study what effect the faults have on the function of the cells. Understanding more about what the EPHB4 gene does and how the gene fault leads to disease may reveal clues for new treatments for lymphoedema in the future.