Understanding Mechanisms of Terminal Erythroid Maturation
This FOA encourages applications that propose hypothesis-driven research to study development of erythroid precursors into mature red blood cells. The aim of this program is to support research efforts to improve our understanding of the molecular mechanisms regulating late stages of erythroid maturation. These studies are needed to identify novel therapeutic targets for use in erythropoietin-resistant anemias characterized by defects in late-stage erythroid maturation. Application Due Date February 1, 2012
Research Scope: This FOA is designed to stimulate and support research efforts to define molecular mechanisms regulating the late stages of erythropoiesis. A further objective is to identify new targets that would improve the therapeutic options for erythropoietin-resistant anemias.
Areas of interest and appropriate topics include but are not limited to those listed below:
- Mechanistic roles of adhesive interactionsand cytokines in the regulation of erythropoiesis in erythroblastic islands.
- The role of central macrophages in ironhomeostasis during erythroid differentiation.
- Mechanisms of the enucleation process and of protein sorting during enucleation.
- The role of motor proteins in the movementof organelles and vacuoles before and during enucleation.
- Mechanisms controlling reticulocyte maturation.
- Reticulocyte maturation as a model forautophagy in other systems.
- Cellular and molecular processes involvedin the clearance of each of the organelles present in late-stageerythroblasts and reticulocytes.
- Regulation of stress erythropoiesis.
- Alterations in erythroblastic islandformation, enucleation, and reticulocyte maturation inerythropoietin-resistant anemias characterized by defects in erythroid maturation.
- Erythropoietin signaling during late stage differentiation and mechanisms of erythropoietin resistance.
- Iron homeostasis in late-stageerythropoiesis: How is (or are) heme synthesis, erythropoietin response, cellular metabolism, and iron availability coordinated within developing
- Model anemia disorders usingpatient-derived induced Pluripotent Stem (iPS) cell lines.