ISOLATION AND CHARACTERIZATION OF EMBRYONIC AND FETAL GLOBIN REGULATORS

In this project we plan to identify and characterize the factors that regulate the globin genes. Even though several factors have been already identified, so far the most wanted, which are the factors that activate the production of the fetal globin genes, have not been detected despite an intensive search. It is well known that the identification of these factors will have a strong impact on the cure of beta-thalassemia, but also sickle cell disease, by allowing the manipulation of the fetal genes with pharmacological or genetics tools and their reactivation in the adult life. This will result in a clinical condition similar to that of the hereditary persistence of fetal hemoglobin, a condition in which a patient affected by beta-thalassemia bears a complete defect in the production of adult hemoglobin, but compensates with increased production of fetal hemoglobin and does not develop clinical signs of anemia. The shut down of fetal hemoglobin production during postnatal life is immediately followed in the majority of thalassemia patients by a severe anemia that requires continuous transfusions. In this project we have presented preliminary evidences suggesting that some factors, isolated in our and in other laboratories, play a role previously unrecognized in the regulation of the globin genes, included the embryonic and fetal globin genes, and may thus be useful in the genetic or pharmacological treatment of thalassemia and sickle cell disease.