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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Heart, Lung, and Blood Research Review Committee B (HLBB)
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Children's Hospital Boston
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Liu, Nan; Hargreaves, Victoria V; Zhu, Qian et al. (2018) Direct Promoter Repression by BCL11A Controls the Fetal to Adult Hemoglobin Switch. Cell 173:430-442.e17
Whitman, Jared C; Paw, Barry H; Chung, Jacky (2018) The role of ClpX in erythropoietic protoporphyria. Hematol Transfus Cell Ther 40:182-188
Mandelbaum, Joseph; Shestopalov, Ilya A; Henderson, Rachel E et al. (2018) Zebrafish blastomere screen identifies retinoic acid suppression of MYB in adenoid cystic carcinoma. J Exp Med 215:2673-2685
Kapp, Friedrich G; Perlin, Julie R; Hagedorn, Elliott J et al. (2018) Protection from UV light is an evolutionarily conserved feature of the haematopoietic niche. Nature 558:445-448
Yamauchi, Takuji; Masuda, Takeshi; Canver, Matthew C et al. (2018) Genome-wide CRISPR-Cas9 Screen Identifies Leukemia-Specific Dependence on a Pre-mRNA Metabolic Pathway Regulated by DCPS. Cancer Cell 33:386-400.e5
Gehrke, Jason M; Cervantes, Oliver; Clement, M Kendell et al. (2018) An APOBEC3A-Cas9 base editor with minimized bystander and off-target activities. Nat Biotechnol 36:977-982
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

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