Abstract

Specific Aims: The zebrafish genome is being sequenced by the Sanger Center, and Drs. Zon and Zhou are participating in the consortium to achieve a high quality assembly of the zebrafish genome sequence by 2006. We propose to comparatively evaluate gene expression patterns, profiles, and function during hematopoiesis in several vertebrate systems, improving our understanding of blood diseases such as anemias and leukemias. 1. Establish and compare gene expression patterns in vertebrate models by using in situ hybridization and microarray assays. 2. Apply bioinformatics tools to find gene regulation networks in animal disease models and human patient samples. 3. Map mutant genes and develop a reverse genetic strategy for zebrafish.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
5P30DK049216-16
Application #
7923142
Study Section
Special Emphasis Panel (ZDK1)
Project Start
Project End
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
16
Fiscal Year
2009
Total Cost
$121,187
Indirect Cost

  Institution

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

  Publications

Vo, Linda T; Kinney, Melissa A; Liu, Xin et al. (2018) Regulation of embryonic haematopoietic multipotency by EZH1. Nature 553:506-510
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
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
Blaser, Bradley W; Zon, Leonard I (2018) Making HSCs in vitro: don't forget the hemogenic endothelium. Blood 132:1372-1378
Cesana, Marcella; Guo, Michael H; Cacchiarelli, Davide et al. (2018) A CLK3-HMGA2 Alternative Splicing Axis Impacts Human Hematopoietic Stem Cell Molecular Identity throughout Development. Cell Stem Cell 22:575-588.e7
Canver, Matthew C; Lessard, Samuel; Pinello, Luca et al. (2017) Variant-aware saturating mutagenesis using multiple Cas9 nucleases identifies regulatory elements at trait-associated loci. Nat Genet 49:625-634
Blaser, Bradley W; Moore, Jessica L; Hagedorn, Elliott J et al. (2017) CXCR1 remodels the vascular niche to promote hematopoietic stem and progenitor cell engraftment. J Exp Med 214:1011-1027
Perlin, Julie R; Robertson, Anne L; Zon, Leonard I (2017) Efforts to enhance blood stem cell engraftment: Recent insights from zebrafish hematopoiesis. J Exp Med 214:2817-2827
Doulatov, Sergei; Vo, Linda T; Macari, Elizabeth R et al. (2017) Drug discovery for Diamond-Blackfan anemia using reprogrammed hematopoietic progenitors. Sci Transl Med 9:
Lessard, Samuel; Francioli, Laurent; Alfoldi, Jessica et al. (2017) Human genetic variation alters CRISPR-Cas9 on- and off-targeting specificity at therapeutically implicated loci. Proc Natl Acad Sci U S A 114:E11257-E11266

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