Red blood cells use hemoglobin protein to carry oxygen throughout the body. Hemoglobin is made up of alpha and beta globin subunits. Sickle cell disease (SCD) is a group of inherited disorders in which people make abnormal sickle hemoglobin that causes red blood cells to be sickle shaped. As a result, sickle shaped red blood cells stick to blood vessel walls and slow or stop blood flow. When this happens, oxygen cannot reach nearby tissue, and patients may experience pain or organ damage.
SCD is a major cause of death and disability worldwide and carries an exceedingly high risk of vascular complications such as stroke, kidney damage, cardiovascular changes, and skin ulcers. Dr. Ackerman’s research focuses on understanding and treating the vascular complications of SCD. His group addresses these questions with basic and clinical research.
In the laboratory, he is studying a genetic factor that changes the severity of SCD. Some people inherit genetic deletions of alpha globin that cause a milder form of anemia called alpha thalassemia. When an individual is born with SCD and alpha thalassemia, they are partially protected against major SCD vascular complications such as stroke and kidney disease. However, the mechanisms of protection are debated.
Alpha globin deletions are thought to protect against SCD vascular complications through beneficial changes in red blood cells. However, the recent discovery that alpha globin is present in endothelial cells that line blood vessels suggests that alpha globin deletions may affect blood vessels directly.
Dr. Ackerman is collaborating with the group that originally discovered alpha globin in endothelial cells to understand how alpha globin deletions affect blood flow and pressure in humans, as well as protect against vascular complications of SCD. Together, they will develop new drugs that target normal alpha globin and recreate the beneficial effects of alpha globin deletions. These drugs may have therapeutic potential in preventing SCD vascular complications.
To complement his laboratory work, Dr. Ackerman has partnered with an international center of excellence for SCD care and research located in Bamako, Mali, to conduct a clinical study to better define the prevalence, complications, and mortality of SCD in African children. It is estimated that 235,000 children are born each year with SCD in sub-Saharan Africa, and 50 to 90 percent of African children with SCD die, often undiagnosed, before age 5. Together, they will introduce newborn screening into a specific geographic area to determine how many births are affected by SCD. They will follow these children over the first five years of life. During this time, they will provide standard care and document and treat any health complications that occur. Results from this study can inform future research efforts and public health policy, as well as improve care for patients with SCD.