In this application for an NIDDK Cooperative Hematology Specialized Core Center (CHSCC) at Boston Children's Hospital (BCH), we seek to support the field of benign hematology research by providing crucial resources to investigators, by bringing together interactive members who will move the field forward and recruit new investigators to the area, by enriching the environment for trainees at all levels (undergraduate, graduate, medical school) and by offering Pilot & Feasibility grants for highly promising innovative projects of junior investigators. The organization and activities of the CHSCC build on an existing NIDDK-funded Center of Excellence in Molecular Hematology that has served the Harvard Medical School community and investigators elsewhere for 15 years. As the existing Center is the sole facility of its kind in the Harvard Medical Area, it represents a focal point for research in benign hematology and a site for training the next generation of investigators. The CHSCC has members at the affiliated institutions of the Harvard Medical School, and is enriched by interactions with T32 hematology training programs at BCH and Brigham & Women's Hospital (BWH) and a Harvard T32 training program in transfusion medicine, and with the Harvard Stem Cell Institute (HSCI). The CHSCC is comprised of three cores, two of which center on the major animal models for hematology research, the mouse (Core A) and zebrafish (Core B). Focus on these two systems leverages the advantages of each, while providing the benefits of synergy from parallel developmental and genetic studies. These cores provide state-of-the-art services for the generation of engineered mice/zebrafish, maintain critical strains that are used in the day-to-day work of the Cores and that are distributed to investigators elsewhere, and export methods by teaching Center members. In addition, these Cores actively develop or incorporate new approaches, including the recently developed CRISPR/cas9 technology for genome editing. In addition, these Cores are active in generating models of human hematologic disorders and encouraging efforts to translate knowledge from these animal models to human. A new third core, CORE C, provides human iPS cell reprogramming, CRISPR/Cas9 for human disease modeling, and consultation on approaches to CRISPR/Cas9 editing of mouse and zebrafish, as well as fee-for-service flow cytometry core that allows for characterization and isolation of hematopoietic cell populations. In aggregate, the three Cores provide investigators with state- of-the-art approaches to hematology and disease, and support innovative and disease-relevant research that will lead to new therapeutic strategies. In addition to these cores, the CHSCC has an Administrative Core that manages communications with the cores, advertises the capabilities of the CHSCC to investigators, and oversees the Enrichment and Pilot & Feasibility Programs. The Enrichment Program includes many educational opportunities for Center members and trainees in the laboratories of members and an active college undergraduate summer program. The Pilot & Feasibility Program has previously supported innovative, promising projects of junior investigators with the hope that these funds will permit obtaining preliminary data for an NIH R01 application or a similar award. As a CHSCC, the impact of the existing NIDDK-funded Center of Excellence can be expanded to promote and support benign hematology research beyond the members of the Center per se. We believe that the CHSCC at BCH will constitute a national resource for hematology research.
The Cooperative Hematology Specialized Core Center (CHSCC) at Boston Children's Hospital (BCH) brings together researchers in the Harvard Medical School and its affiliated institutions to study how our blood cells are formed, how they are altered in major diseases affecting blood cells, and how new therapies can be developed to benefit patients. To reach these goals, we utilize two animal models, mice and zebrafish, that have been extremely useful in studies of normal blood cells and human disease, and also employ iPS cell reprogramming to create human disease models ?in the dish? with recent CRISPR/Cas9 gene editing. In addition, the CHSCC focuses on training new investigators, distributing important reagents and animals to other laboratories, and on distributing new knowledge to the entire community of blood researchers. We believe that the CHSCC at BCH constitutes a national resource for hematology research.
| 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 |
| Rodriguez-Fraticelli, Alejo E; Wolock, Samuel L; Weinreb, Caleb S et al. (2018) Clonal analysis of lineage fate in native haematopoiesis. Nature 553:212-216 |
| Kapp, Friedrich G; Perlin, Julie R; Hagedorn, Elliott J et al. (2018) Protection from UV light is an evolutionarily conserved feature of the haematopoietic niche. Nature 558:445-448 |
| Kulkeaw, Kasem; Inoue, Tomoko; Ishitani, Tohru et al. (2018) Purification of zebrafish erythrocytes as a means of identifying a novel regulator of haematopoiesis. Br J Haematol 180:420-431 |
| Schlaeger, Thorsten M (2018) Nonintegrating Human Somatic Cell Reprogramming Methods. Adv Biochem Eng Biotechnol 163:1-21 |
| Wattrus, Samuel J; Zon, Leonard I (2018) Stem cell safe harbor: the hematopoietic stem cell niche in zebrafish. Blood Adv 2:3063-3069 |
| Vo, Linda T; Kinney, Melissa A; Liu, Xin et al. (2018) Regulation of embryonic haematopoietic multipotency by EZH1. Nature 553:506-510 |
| 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 |
| 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 |
| Henninger, Jonathan; Santoso, Buyung; Hans, Stefan et al. (2017) Corrigendum: Clonal fate mapping quantifies the number of haematopoietic stem cells that arise during development. Nat Cell Biol 19:142 |
Showing the most recent 10 out of 47 publications
