click here for more information.
Phone: (212) 570-3463
Our laboratory focus is erythropoiesis and its related regulatory parameters in human and animal models. Iron, heme, and globin synthesis are tightly coordinated for hemoglobin production to prevent the precipitation of excess components. Dysregulated iron metabolism results either in anemia or hemochromatosis. Ineffective erythropoiesis leads to diseases such as beta-thalassemia and myelodysplastic syndrome. Our projects are designed to study the biophysical, structural, genetic features of erythroid cells and functions of peptide such as hepcidin that regulate body iron flows to understand the crosstalk between iron regulation and erythroid cell growth and maturation.
Beta-thalassemia is a disease caused by a mutation in the beta-globin gene which results in ineffective erythropoiesis and anemia. In the past, we have demonstrated that hemoglobin in beta-thalassemic mice increased with exogenous iron administration despite the massive systemic iron overload and resulted from the expansion of extramedullary erythropoiesis in the liver. We hypothesize that ineffective erythropoiesis may be associated with insufficient iron transporter protein ? transferrin ? to accommodate the considerable expanded erythropoiesis observed in beta-thalassemia. Giving beta-thalassemic mice additional transferrin showed normalized labile plasma iron concentrations, increased hepcidin expression, normalized red blood cell survival and increased hemoglobin production; this treatment concomitantly decreased reticulocytosis, erythropoietin abundance and splenomegaly. This study suggests that transferrin could be beneficial in patients with beta-thalassemia. The current standard treatment for these patients is transfusion followed by iron chelation therapy. It is our goal to provide preclinical evidence for the use of transferrin to safely and effectively ameliorate symptoms in beta-thalassemia. We continue to analyze the mechanisms underlying this intriguing observation.
Hepcidin regulation by erythropoietic activity has been proposed on the basis of the observation that a secreted substance that functions as an ?erythroid regulator? likely results in hepcidin suppression in beta-thalassemia. The nature of the erythroid regulator of hepcidin is incompletely understood, and the role of hepcidin in response to and recovery from blood transfusion remain to be determined. We are looking closely at the timeline and mechanism of erythropoiesis-induced suppression of hepcidin after double red cell donation in normal donors. Determining the trough of hepcidin suppression after phlebotomy may help delineate the stage of erythroid differentiation involved in hepcidin suppression to enable us to efficiently identify iron deficient donors before they become anemic, permit the identification of those who could benefit from iron replacement, and predict future hemoglobin deferral from blood donation.