Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL032262-13
Application #
2216992
Study Section
Heart, Lung, and Blood Research Review Committee B (HLBB)
Project Start
1983-01-01
Project End
1996-06-30
Budget Start
1994-08-05
Budget End
1995-06-30
Support Year
13
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

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
Uenishi, Gene I; Jung, Ho Sun; Kumar, Akhilesh et al. (2018) NOTCH signaling specifies arterial-type definitive hemogenic endothelium from human pluripotent stem cells. Nat Commun 9:1828
Yu, Shan-He; Zhu, Kang-Yong; Zhang, Fan et al. (2018) The histone demethylase Jmjd3 regulates zebrafish myeloid development by promoting spi1 expression. Biochim Biophys Acta Gene Regul Mech 1861:106-116
Parada-Kusz, Margarita; Penaranda, Cristina; Hagedorn, Elliott J et al. (2018) Generation of mouse-zebrafish hematopoietic tissue chimeric embryos for hematopoiesis and host-pathogen interaction studies. Dis Model Mech 11:
Rost, Megan S; Shestopalov, Ilya; Liu, Yang et al. (2018) Nfe2 is dispensable for early but required for adult thrombocyte formation and function in zebrafish. Blood Adv 2:3418-3427
Lahvic, Jamie L; Ammerman, Michelle; Li, Pulin et al. (2018) Specific oxylipins enhance vertebrate hematopoiesis via the receptor GPR132. Proc Natl Acad Sci U S A 115:9252-9257
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

Showing the most recent 10 out of 215 publications