A CENTER OF MOLECULAR HEMATOLOGY

项目摘要/摘要 在波士顿NIDDK合作血液学专业核心中心(CHSCC)的这份申请中 儿童医院(BCH)，我们寻求通过提供关键的 向调查人员提供资源，将互动成员聚集在一起，这些成员将推动该领域的发展并招募 该地区的新调查人员，通过丰富各级受训人员(本科生、研究生、 医学院)，并为极具前景的青少年创新项目提供试点和可行性资助 调查人员。CHSCC的组织和活动建立在现有的NIDDK资助的 为哈佛医学院社区和研究人员服务的卓越分子血液学 在其他地方呆了15年。由于现有的中心是哈佛医学区唯一的此类设施，它 是良性血液学研究的焦点和培训下一代血液学的场所 调查人员。CHSCC在哈佛医学院附属机构中有成员，并 通过与BCH和Brigham&Women医院的T32血液学培训计划的互动而丰富 (BWH)和哈佛T32输血医学培训计划，以及与哈佛干细胞研究所的合作 (HSCI)。CHSCC由三个核心组成，其中两个核心以主要动物模型为中心 血液学研究，老鼠(核心A)和斑马鱼(核心B)。专注于这两个系统，利用 各有优势，同时提供并行发展和遗传研究的协同效益。 这些核心为工程小鼠/斑马鱼的产生提供最先进的服务，维护关键 在岩心日常工作中使用的菌株，并分发给其他地方的调查人员， 并按教学中心成员导出方法。此外，这些核心积极开发或纳入新的 方法，包括最近开发的用于基因组编辑的CRISPR/Cas9技术。此外，这些 CORE在建立人类血液病模型方面很活跃，并鼓励努力翻译 从这些动物模型到人类的知识。新的第三个核心，核心C，提供了人类iPS细胞 重新编制方案，CRISPR/CAS9用于人类疾病建模，以及关于CRISPR/CAS9办法的协商 编辑鼠标和斑马鱼，以及允许表征的收费流式细胞仪核心 和分离造血细胞群体。总体而言，这三个核心为调查人员提供了状态- 血液学和疾病的最先进方法，并支持创新和与疾病相关的研究 将导致新的治疗策略。除了这些核心，CHSCC还有一个管理核心， 管理与核心的通信，向调查人员通告CHSCC的功能，以及 监督浓缩项目和试点及可行性项目。浓缩计划包括许多 中心成员和实习生在成员和活跃分子的实验室接受教育的机会 大学本科生暑期计划。试点和可行性计划此前曾支持创新、 初级调查人员有希望的项目，希望这些资金将允许获得初步数据 申请NIH R01或类似奖项。作为CHSCC，现有的NIDDK资助的中心 卓越可以扩大到促进和支持良性血液学研究，超出 中心本身。我们相信，BCH的CHSCC将成为全国血液学研究的资源。

Project Summary/Abstract 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.