Defining the role of pro-resolving mediators in reprogramming stem cell function in sickle cell disease

Sickle cell disease (SCD) is England's most common inherited condition, affecting around 15,000 people and heavily concentrated in East London boroughs such as Tower Hamlets, Newham and Hackney, where a large share of residents are of African or Caribbean origin. London accounts for roughly 75% of England's SCD hospital admissions, and it remains a major cause of pain, illness and early death, cutting average life expectancy to just 40–60 years.

A change in the haemoglobin gene makes red blood cells stiff and “sickle-shaped.” These cells block blood vessels, break apart easily and trigger constant inflammation. Over time this inflammation damages the bone marrow, where blood is made, weakening the stem cells that keep blood healthy. As a result, people with SCD struggle to make enough healthy cells, a problem for curative treatments like gene therapy that depend on strong, functional stem cells.

Our research asks whether resolving this inflammation can protect the blood-forming stem cells SCD erodes. Specialised pro-resolving mediators (SPMs), molecules made from omega-3 fatty acids that act as the body's natural “switch” to turn off inflammation, are central. Our early findings show people with SCD have dysregulated SPM levels in their bone marrow, and that restoring them may improve stem-cell function. The project will define how individual SPMs act on sickle-cell stem cells to calm the inflamed marrow, strengthen these stem cells and make curative therapies safer and more accessible for the East London communities most affected by SCD.