Following the TRAIL to pulmonary arterial hypertension

Defining cellular and molecular interactions in the OPG/TRAIL pathway in pulmonary arterial hypertension

In this Senior Fellowship, Dr Lawrie, based at the University of Sheffield, will investigate the role of two proteins TRAIL and OPG in pulmonary arterial hypertension (PAH), a rare but devastating condition where high blood pressure in the arteries of the lungs leads to low oxygen levels and heart failure. The disease is driven by unchecked vascular cell growth within the bloods vessels of the lungs, which causes narrowing of the vessels. Despite modern drugs there is still no cure other than a lung transplant. The precise cell and molecular mechanisms leading to PAH and driving the disease remain poorly understood. Dr Lawrie and his team were the first to describe a role for two proteins in PAH called TRAIL and OPG. He has shown that these proteins are increased in PAH and that they cause vascular cells to overgrow. He has also shown that anti-TRAIL and anti-OPG treatments reverse experimental PAH. Dr Lawrie will study how TRAIL and OPG interact to cause blood vessel overgrowth in PAH. This information could lead to development of novel therapies targeting these proteins.