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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Center Core Grants (P30)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-G (O3))
Program Officer
Bishop, Terry Rogers
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Children's Hospital Boston
United States
Zip Code
Kumar, Lalit; Chou, Janet; Yee, Christina S K et al. (2014) Leucine-rich repeat containing 8A (LRRC8A) is essential for T lymphocyte development and function. J Exp Med 211:929-42
Alcaraz-Perez, Francisca; Garcia-Castillo, Jesus; Garcia-Moreno, Diana et al. (2014) A non-canonical function of telomerase RNA in the regulation of developmental myelopoiesis in zebrafish. Nat Commun 5:3228
Hagedorn, Elliott J; Durand, Ellen M; Fast, Eva M et al. (2014) Getting more for your marrow: boosting hematopoietic stem cell numbers with PGE2. Exp Cell Res 329:220-6
Musso, Gabriel; Tasan, Murat; Mosimann, Christian et al. (2014) Novel cardiovascular gene functions revealed via systematic phenotype prediction in zebrafish. Development 141:224-35
Sun, Jianlong; Ramos, Azucena; Chapman, Brad et al. (2014) Clonal dynamics of native haematopoiesis. Nature 514:322-7
Das, Partha Pratim; Shao, Zhen; Beyaz, Semir et al. (2014) Distinct and combinatorial functions of Jmjd2b/Kdm4b and Jmjd2c/Kdm4c in mouse embryonic stem cell identity. Mol Cell 53:32-48
Mirabello, Lisa; Macari, Elizabeth R; Jessop, Lea et al. (2014) Whole-exome sequencing and functional studies identify RPS29 as a novel gene mutated in multicase Diamond-Blackfan anemia families. Blood 124:24-32
Canver, Matthew C; Bauer, Daniel E; Dass, Abhishek et al. (2014) Characterization of genomic deletion efficiency mediated by clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 nuclease system in mammalian cells. J Biol Chem 289:21312-24
Xie, Huafeng; Xu, Jian; Hsu, Jessie H et al. (2014) Polycomb repressive complex 2 regulates normal hematopoietic stem cell function in a developmental-stage-specific manner. Cell Stem Cell 14:68-80
Shinoda, Gen; De Soysa, T Yvanka; Seligson, Marc T et al. (2013) Lin28a regulates germ cell pool size and fertility. Stem Cells 31:1001-9

Showing the most recent 10 out of 30 publications