Reducing lipid scrambling in sickle cell disease

Phosphatidylserine exposure in red blood cells from patients with sickle cell disease:  The interaction between Ca2+ and oxidation

Dr John Gibson and his colleagues at the University of Cambridge are investigating how to reduce complications associated with sickle cell disease (SCD). People with SCD produce unusually shaped red blood cells that don't live as long as healthy blood cells and that can become stuck in blood vessels. In healthy people, a lipid called phosphatidylserine is usually located inside cell membranes. In red blood cells from people with SCD, more phosphatidylserine is outside the cell than normal; this is called lipid scrambling. Lipid scrambling shortens the lifespan of red blood cells causing anaemia, and encourages blood clotting. Small blood vessels become blocked by clots, leading to blood vessel disease, pain and organ damage including stroke. Lipid scrambling can be caused by several pathways, but the main signal is calcium. Calcium acts together with damage caused by potentially harmful molecules called oxidants to boost scrambling. In this project, Dr Gibson will characterise the interaction between oxidant damage and calcium during lipid scrambling in sickle cells, and work out if antioxidants, calcium blockers or other drugs, some already being used in people with SCD, can reduce scrambling. Because these treatments are already either in use or in clinical trials, this project could translate into the clinic to benefit patients relatively quickly.