Solomon Ofori-Acquah, Ph.D.
Sickle Cell Disease
Emory University
Morehouse School of Medicine
Recruited: 2024
The leading cause of premature death for people with sickle cell disease is a condition called acute chest syndrome (ACS). Solomon Ofori-Acquah made a groundbreaking discovery on what brings on this often-fatal event, and it is one of several important contributions he has made in his exploration of the disease.
About half of people with sickle cell disease will have ACS at least once, navigating high fever, intense coughing and extreme difficulty breathing. In 2009, while at Emory, Ofori-Acquah hypothesized that ACS reflected a disruption in the endothelium, a thin layer of cells that lines the inside of blood vessels to regulate the flow of fluids between vessel and tissue. He had studied the endothelium for several years, and at Emory, Ofori-Acquah had started a research enterprise on endothelial biology.
After a series of experiments, Ofori-Acquah made a connection between the endothelial barrier and heme, iron-rich molecules released when hemoglobin breaks down. After injecting a low dose of heme into the blood of mouse models, he saw that the mice went into respiratory distress almost immediately and died. The cause of death was excessive fluid in the lungs brought on by disruption of the endothelial barrier – acute chest syndrome.
Ofori-Acquah’s 2013 paper in Journal of Clinical Investigation chronicled these events. He and colleagues also reported testing a potential way to stop the effects of excessive heme – recombinant hemopexin (rhHx). Hemopexin is a protein that binds to heme and helps remove it from the bloodstream; they found that administering rhHx to sickle mice after they had been exposed to heme significantly reduced the ACS lung injury. The finding suggested that rhHx could be a promising treatment for preventing ACS in patients with SCD.
Ofori-Acquah’s paper marked the beginning of new research that strengthened the connection between excess heme in the blood and ACS. Today, these studies continue to inform development of treatments for acute chest syndrome as well as procedures to prevent it.
Following this discovery, Ofori-Acquah went on to expand his sickle cell research efforts on a global basis. After leaving Emory in 2013, he founded an international hematology center at the University of Pittsburgh; five years later, he took an additional part-time position at the University of Ghana, working with a clinical research team. These endeavors helped establish the largest patient cohort study of sickle cell disease in the world: SickleGenAfrica Network. More than 7,000 children and adults in three African countries take part in the massive study, and the effort resulted in the largest biobank of sickle cell disease specimens ever established.
Part of that study involves exploring genetic variants that reveal clues in the clinical presentation of sickle cell disease. More than 2,300 patients in the Ghana cohort have had differences in their genetic makeup mapped through a process called whole genome genotyping; of these, over 500 are having their entire DNA sequenced. The effort will yield an enormous and highly precise data set, revealing differences all the way down to single DNA units called nucleotides.
Ofori-Acquah aims to translate these findings into precision medicine approaches for children and adults with sickle cell disease.
GRA and member universities Emory University and Morehouse School of Medicine, along with Children’s Healthcare of Atlanta, recruited Ofori-Acquah in 2024 to lead the Georgia Solve Sickle Cell Initiative. Ofori-Acquah will spearhead an ambitious research effort that brings Georgia sickle cell patients into his global cohort study as well as explores new avenues for treatments and a cure.
In addition to deepening understanding of sickle cell disease, Ofori-Acquah has made advances in vascular biology, genomics and breast cancer. One significant contribution came in 2004, when his research team identified a marker for the prognosis of breast cancer. He had previously shown that this marker – a molecule (ALCAM/CD166) that adheres to leukocyte cells – controls the movement of blood cells across blood vessels. That finding proved consequential years later: It informed Ofori-Acquah’s hypothesis about heme and acute chest syndrome.
Research
- Sickle cell disease and acute chest syndrome
- Endothelial barrier function
- Mechanisms of neutralizing erythroid danger associated molecular pattern (eDAMP) molecules
- Developmental, genetic and epigenetic regulation of naturally occurring proteins that protect the body from hemolysis.
Choosing Georgia
“Returning to Georgia to lead the Solve Sickle Cell Initiative was a relatively easy decision, given the commitment made by the state to build a sustainable partnership with multiple stakeholders with a global impact.”
