A major focus of the laboratory involves studies of erythropoiesis in real-time as stem cells undergo erythroid commitment and differentiation. It is hypothesized that these studies will be useful for translational research aimed at malaria, hemoglobinopathies, anemia, leukemia, and iron pathologies. These studies have developed over several years with a primary focus upon the use of flow cytometry to identify, characterize and isolate the developmentally-staged cells. Flow cytometry has become sufficiently robust in recent years to provide analyses beyond the simple identification of the cells to include transcription, organelle development, and membrane specialization. Once purified, molecular biology applications have been developed for transcriptome analyses and quantitative analyses in single cells. Further, these approaches have been modified to include analyses of erythrocytes sampled directly patient volunteers. Based upon interests in hemoglobin regulation, a genomics project was undertaken to determine differences between the fetal and adult reticulocyte transcriptome. Once candidate genes are identified that may possess increased clinical relevance, the analyses are focused upon gene discovery and characterization.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2010
Total Cost
$342,301
Indirect Cost
City
State
Country
Zip Code
de Vasconcellos, Jaira F; Lee, Y Terry; Byrnes, Colleen et al. (2016) HMGA2 Moderately Increases Fetal Hemoglobin Expression in Human Adult Erythroblasts. PLoS One 11:e0166928
Byrnes, Colleen; Lee, Y Terry; Meier, Emily R et al. (2016) Iron dose-dependent differentiation and enucleation of human erythroblasts in serum-free medium. J Tissue Eng Regen Med 10:E84-9
Lee, Y Terry; de Vasconcellos, Jaira F; Byrnes, Colleen et al. (2015) Erythroid-Specific Expression of LIN28A Is Sufficient for Robust Gamma-Globin Gene and Protein Expression in Adult Erythroblasts. PLoS One 10:e0144977
Glushakova, Svetlana; Balaban, Amanda; McQueen, Philip G et al. (2014) Hemoglobinopathic erythrocytes affect the intraerythrocytic multiplication of Plasmodium falciparum in vitro. J Infect Dis 210:1100-9
Meier, Emily Riehm; Wright, Elizabeth C; Miller, Jeffery L (2014) Reticulocytosis and anemia are associated with an increased risk of death and stroke in the newborn cohort of the Cooperative Study of Sickle Cell Disease. Am J Hematol 89:904-6
Lee, Y Terry; Kim, Ki Soon; Byrnes, Colleen et al. (2013) A synthetic model of human beta-thalassemia erythropoiesis using CD34+ cells from healthy adult donors. PLoS One 8:e68307
Miller, Jeffery L (2013) Iron deficiency anemia: a common and curable disease. Cold Spring Harb Perspect Med 3:
Meier, Emily Riehm; Byrnes, Colleen; Lee, Y Terry et al. (2013) Increased Reticulocytosis during Infancy Is Associated with Increased Hospitalizations in Sickle Cell Anemia Patients during the First Three Years of Life. PLoS One 8:e70794
Lee, Y Terry; de Vasconcellos, Jaira F; Yuan, Joan et al. (2013) LIN28B-mediated expression of fetal hemoglobin and production of fetal-like erythrocytes from adult human erythroblasts ex vivo. Blood 122:1034-41
Zafrani, Lara; Gerotziafas, Grigoris; Byrnes, Colleen et al. (2012) Calpastatin controls polymicrobial sepsis by limiting procoagulant microparticle release. Am J Respir Crit Care Med 185:744-55

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