This Program Project examines the developmental biology of human erythropoiesis. In Project I, we investigate methods of progenitor purification and the regulation of fetal hemoglobin synthesis in erythroblasts derived from progenitors. In Project V, we continue our study of the function of antibodies to specific regions of erythropoietin in an attempt to define the regions of the hormone that induce the replication and terminal differentiation of progenitor cells and define its receptor. In Project II, we begin a major new undertaking, the transfer of genes into hematopoietic progenitor cells, focusing on dihydrofolate reductase and adenosine deaminase as prototypes. In Project IV, we analyze the appearance of erythroid specific proteins on developing murine and human erythroid cells, with particular reference to the onset of expression of fibronectin receptors. In Project III, we study the pathophysiology of membrane disturbances in the thalassemia syndromes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL032262-09
Application #
3098281
Study Section
Heart, Lung, and Blood Research Review Committee B (HLBB)
Project Start
1983-01-01
Project End
1991-06-30
Budget Start
1990-08-01
Budget End
1991-06-30
Support Year
9
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Blaser, Bradley W; Zon, Leonard I (2018) Making HSCs in vitro: don't forget the hemogenic endothelium. Blood 132:1372-1378
Kafina, Martin D; Paw, Barry H (2018) Using the Zebrafish as an Approach to Examine the Mechanisms of Vertebrate Erythropoiesis. Methods Mol Biol 1698:11-36
Clement, Kendell; Farouni, Rick; Bauer, Daniel E et al. (2018) AmpUMI: design and analysis of unique molecular identifiers for deep amplicon sequencing. Bioinformatics 34:i202-i210
Liu, Frances D; Tam, Kimberley; Pishesha, Novalia et al. (2018) Improving hematopoietic recovery through modeling and modulation of the mesenchymal stromal cell secretome. Stem Cell Res Ther 9:268
Huang, Nai-Jia; Lin, Ying-Cing; Lin, Chung-Yueh et al. (2018) Enhanced phosphocholine metabolism is essential for terminal erythropoiesis. Blood 131:2955-2966
Schoonenberg, Vivien A C; Cole, Mitchel A; Yao, Qiuming et al. (2018) CRISPRO: identification of functional protein coding sequences based on genome editing dense mutagenesis. Genome Biol 19:169
Lessard, Samuel; Beaudoin, Mélissa; Orkin, Stuart H et al. (2018) 14q32 and let-7 microRNAs regulate transcriptional networks in fetal and adult human erythroblasts. Hum Mol Genet 27:1411-1420
Esrick, Erica B; Bauer, Daniel E (2018) Genetic therapies for sickle cell disease. Semin Hematol 55:76-86
Yien, Yvette Y; Shi, Jiahai; Chen, Caiyong et al. (2018) FAM210B is an erythropoietin target and regulates erythroid heme synthesis by controlling mitochondrial iron import and ferrochelatase activity. J Biol Chem 293:19797-19811
Wattrus, Samuel J; Zon, Leonard I (2018) Stem cell safe harbor: the hematopoietic stem cell niche in zebrafish. Blood Adv 2:3063-3069

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