Structural and functional characterization of Red Blood cells in physiological and pathologichal conditions

Sickle cell disease is a genetic disorder caused by a single point mutation in the b-globin gene, resulting in a functional and structural defect of hemoglobin. When deoxygenated, this abnormal hemoglobin (i.e., HbS) may polymerize, which turn causes a mechanical distortion of red blood cell in a crescent-like shape. Sickled red blood cells are fragile and rigid, which cause chronic hemolytic anemia and repeated vaso-occlusive crises, respectively. Chronic hemolysis also plays a key role in the development of chronic organ damages.

The aging process of red blood cells in sickle cell disease is enhanced. This process, called eryptosis, is characterized by cell shrinkage and membrane scrambling, Ca2+ influx, phosphatidylserine exposure in the outer membrane, production and release of microparticles from cell membrane, accumulation of reactive oxygen species. We plan to investigate the associations between eryptosis, red blood cell rheological profiles, hemolysis and the clinical severity of the disease in a cohort of sickle cell patients.

For the other part of the project at Erytech Pharma Company, the aim is to study the effect of encapsulation of therapeutic molecules into mouse red blood cells, and to compare with the results obtained on human red blood cells.