This application serves as a competitive reapplication ofthe Center of Excellence in Molecular Hematology at the Children's Hospital Boston. The goal of the Center is to facilitate fundamental Studies of the blood system in the two most tractable model organisms~the mouse and zebrafish. Focus on these two systems leverages the advantages of each, while providing the benefits of synergy from parallel developmental and genetic studies. The Center is comprised of 3 cores that serve the users within the Harvard Medical area and elsewhere. CORE A provides consultation and resources for generation of engineered mice and ES cells, distribution of mutant strains and various CRE-expressing and CRE-reporter lines, and assistance in analysis of mouse phenotypes and bone marrow transplantation CORE B is a zebrafish core that supports genetics and developmental studies of hematopoiesis. CORE B maintains numerous mutant zebrafish stocks, and provides education to users. CORE C is a new core focused on technology aimed at supporting research on hematopoietic stem cells and individual blood lineages. One part of CORE C is a fee-for-service flow cytometry core that allows for characterization and isolation of hematopoietic cell populations. A complementary part of CORE C is devoted to technology development and dissemination of methodologies for genomic analyses of small numbers of cells. Specifically, CORE C will validate antibodies for ChlP-sequencing and ChlP-Chip approaches, and improve methods for application of these and other methods (such as genome-wide assessment of DNA methylation) to limited numbers of cells isolated by FACS. CORE C will fulfill an unmet need in the hematology community. In addition to the CORES, the Center will provide an Enrichment Program consisting of workshops and Internet meetings, as well as a Pilot Grant Program designed to support emerging investigators or to recruit new investigators to hematology.
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 ofthe NIDDK hematology program.
|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 Î²-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-Î± 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|
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