Switching Gear: Hemoglobin switching throughout erythropoiesis

Red blood cells are the most abundant cells in our bodies and supply our tissues with oxygen. In order to transport oxygen these cells are packed with hemoglobin molecules. Defects to the genes encoding these molecules can result in premature breakdown of red blood cells, which results in too few red bloods also called anemia. People with severe forms of anemia can even become dependent on recurring blood transfusions. This thesis aims to find alternative treatments for anemias by detailed investigation of the process through which red blood cells are formed and the regulation of the different hemoglobin genes in this process. It describes the optimization of a cell culture medium that helps to grow large amounts of red cells for transfusion purposes and it describes a possible role for environmental signals in the control of hemoglobin gene expression. Additionally, outlines how specific variants of KLF1, a regulatory protein, alter hemoglobin expression in both human and mice. Combined these observations provide building blocks for development of future treatments for anemia.