A Center of Molecular Developmental Hematopoiesis: The Center of Excellence in Molecular Hematology was established ~15 years ago by the Principal Investigator (S.H. Orkin) and the co-investigator (L.I. Zon). The Center was based on the premise that parallel genetic investigation of the major vertebrate model organisms, mice and zebrafish, would advance our understanding of fundamental aspects of blood cell formation, provide a platform for new insights into disease, and stimulate broader hematological research among our colleagues and trainees. Moreover, the work of the Center, we hoped, would provide fundamental results that could be translated to the treatment of clinical problems. Our experience, we believe, validates the original premise. The Center has provided a focus for research activities and greatly benefited the research community through the services provided by its Cores. Two Cores have remained constant since the Center's inception. CORE A is a Mouse Embryonic Stem (ES) Cell and Gene Targeting Core that has supported investigators through education and consultation, oocyte and blastocyst microinjections, assistance in embryo and hematological phenotyping, and de novo ES cell derivation. The menu of available services provided extends well beyond that offered by conventional mouse cores. CORE B is a zebrafish core that serves investigators both locally and internationally. CORE B maintains numerous mutant strains, as well as unique strains (such as transparent Casper fish). CORE B has been instrumental in supporting zebrafish screening efforts and also the work of junior, emerging investigators as well as researchers from other disciplines who seek to use the zebrafish as a model organism. CORE C has traditionally provided resources for rapid genetic mapping of zebrafish genes and bioinformatics analysis. With the maturity of the zebrafish genome project and general availability of informatics support in the Harvard Medical area, we have decided in the current renewal application to redirect the focus of CORE C to provide technological support to investigators in two critical areas. First, CORE C will house and further develop a newly established flow cytometry (FACS) core that provides fee-for-service analysis and isolation of cell populations. Second, CORE C will provide a new service to the community: validation of antibodies and methodologies for chromatin immunoprecipitation (ChIP) and ChlP-chip or ChIP sequencing. In parallel, CORE C will explore and then disseminate approaches to minimize sample size in an effort to facilitate genomic and epigenetic studies on limited populations, such as HSCs. Access to the services of the Center is available to virtually all investigators who approach the Center with research projects that fall within the broad umbrella of hematology research and can be enhanced by the services provided. We have a non-exclusive view of membership. Except for FACS analysis and cell preparation, all services are without charge.
Our aim i s to encourage use of the resources of the Center and to eliminate barriers to investigators, particularly to junior investigators. To date, we have been able to manage the demand for services.

Public Health Relevance

Research in the area of developmental molecular hematology is fundamental to an improved understanding of disorders affecting blood cell production and function. Such research is central to the mission of the NIDDK hematology program.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
5P30DK049216-21
Application #
8695326
Study Section
Special Emphasis Panel (ZDK1-GRB-G (O3))
Program Officer
Bishop, Terry Rogers
Project Start
1997-09-05
Project End
2015-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
21
Fiscal Year
2014
Total Cost
$1,131,819
Indirect Cost
$471,624
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Mangum, Joshua E; Hardee, Justin P; Fix, Dennis K et al. (2016) Pseudouridine synthase 1 deficient mice, a model for Mitochondrial Myopathy with Sideroblastic Anemia, exhibit muscle morphology and physiology alterations. Sci Rep 6:26202
Rowe, R Grant; Wang, Leo D; Coma, Silvia et al. (2016) Developmental regulation of myeloerythroid progenitor function by the Lin28b-let-7-Hmga2 axis. J Exp Med 213:1497-512
Luc, Sidinh; Huang, Jialiang; McEldoon, Jennifer L et al. (2016) Bcl11a Deficiency Leads to Hematopoietic Stem Cell Defects with an Aging-like Phenotype. Cell Rep 16:3181-94
Nasrallah, Rabab; Fast, Eva M; Solaimani, Parham et al. (2016) Identification of novel regulators of developmental hematopoiesis using Endoglin regulatory elements as molecular probes. Blood 128:1928-1939
Masuda, Takeshi; Wang, Xin; Maeda, Manami et al. (2016) Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin. Science 351:285-9
Reddy, Pavankumar N G; Radu, Maria; Xu, Ke et al. (2016) p21-activated kinase 2 regulates HSPC cytoskeleton, migration, and homing via CDC42 activation and interaction with β-Pix. Blood 127:1967-75
CHARGE Consortium Hematology Working Group (2016) Meta-analysis of rare and common exome chip variants identifies S1PR4 and other loci influencing blood cell traits. Nat Genet 48:867-76
Kim, Peter Geon; Canver, Matthew C; Rhee, Catherine et al. (2016) Interferon-α signaling promotes embryonic HSC maturation. Blood 128:204-16
Hoban, Megan D; Orkin, Stuart H; Bauer, Daniel E (2016) Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease. Blood 127:839-48
Bauer, Daniel E; Orkin, Stuart H (2015) Hemoglobin switching's surprise: the versatile transcription factor BCL11A is a master repressor of fetal hemoglobin. Curr Opin Genet Dev 33:62-70

Showing the most recent 10 out of 81 publications