An shRNA Screen for the Discovery of Suppressors of Fetal Hemoglobin

β-thalassemia and SCD are among the most common monogenic disorders with more than 300.000 patients born each year worldwide. To date, there is no satisfactory cure for these diseases as the existing therapeutic approaches are either too expensive or not completely effective. Reactivation of the fetal γ-globin can ameliorate the symptoms of these diseases as γ-globin can effectively replace the mutated or deficient β-globin. Thus targeting relevant transcription factors to prevent or reverse the γ to β-globin switch could be a powerful strategy for the treatment of β-thalassemia and SCD. Despite recent progress in the field, the exact mechanisms of hemoglobin switching from fetal to adult are not fully understood, but most likely involve developmental stage-specific changes in transcription factors and/or chromatin remodeling complexes. The aim of this thesis is to identify additional factors involved in this process and unravel the signal transduction mechanisms that activate the γ-globin suppression.