Research Projects

Thalassemia is one of the commonest single-gene disorders representing a major health problem in India and the world. Eastern India is severely affected by thalassemia variant Hb E-beta-thalassemia (Hb E/β-thalassemia) which accounts for approximately 50% of the severe β-thalassemia worldwide. Thalassemia is characterized by reduced or absent synthesis of β-globin chains, leading to the erythropoietin (EPO)-driven expansion of early-stage erythroid precursors, apoptosis of late-stage precursors and red blood cells, and anemia. Ineffective erythropoiesis results in parenchymal iron overload. This problem is often worsened by imperative repeated blood transfusion in thalassemia. Iron (Fe) overload is a major contributor to morbidity and mortality in thalassemic patients despite the availability of chelation therapy. Children are sensitive to defective erythropoiesis and blood transfusion starts at an early age. Erythroid regulator erythroferrone (ERFE) suppresses hepcidin (systemic Fe sensor) expression, thereby increasing Fe availability via increased intestinal absorption and recycling from splenic macrophages for developing erythroid progenitors. ERFE is a hormone produced by erythroblasts in the bone marrow in response to EPO. ERFE acts in stress-specific erythropoiesis rather than baseline erythropoiesis regulation. Recent evidence suggest that another erythroid regulator hepatokine fibrinogen-like protein 1 (FGL1, secreted by hepatocytes) suppress hepcidin expression in thalassemic mice. However, the role of FGL1 in clinical settings remains to be clarified. An early increase of ERFE followed by FGL1 in murine model suggests that these new erythroid regulators may exacerbate iron overload in thalassemic patients. Currently used serum parameters for assessment of iron toxicity especially ferritin including hepcidin are acute phase reactant and gets induced in inflammatory and chronic conditions. So, our research aims to determine blood ERFE and FGL1 levels/expression along with ferritin and or hepcidin in children with thalassemia which will help in the early prediction of Fe overload states in transfusion and non-transfusion-dependent thalassemia and also help in monitoring different degrees of Fe overload and its complications in such patients. Differential regulation of ERFE and FGL1 could serve as potential clinical biomarkers for assessing impaired erythropoiesis and Fe overload in thalassemia. Assessment of the severity of Fe overload in the children diagnosed with Hb E/β-thalassemia and β-TM will help in designing novel therapeutic targets against ERFE and or FGL1.