Our laboratory is studying signaling within the erythroid progenitor and precursor cells during erythropoiesis, as well as in mature red blood cells. We specifically focus on signals conducted by Rac GTPases, which are members of the Rho family and Ras superfamily. They switch between the inactive GDP-bound form and the active GTP-bound form to regulate a wide spectrum of cellular functions. They have been shown to play unique and overlapping roles in hematopoietic and blood cells (Mulloyet al., Blood. 115:936–947. 2010). They control actin cytoskeleton, cell motility, vesicular transport pathways, reactive oxygen species production, as well as cell adhesion and migration, proliferation and survival.
We explore the role of Rac GTPases in erythropoiesis and mature RBCs in gene-targeted mice where Rac1 and Rac2 GTPases have been deleted from the hematopoietic cells. We also study the role of Rac GTPases in generation of reactive oxygen species (ROS) within human erythrocytes from patients with sickle-cell disease.