A CENTER OF MOLECULAR HEMATOLOGY

项目概要/摘要 在此申请NIDDK合作血液学专业核心中心（CHSCC）在波士顿 儿童医院（BCH），我们寻求支持良性血液学研究领域，提供关键的 通过将互动成员聚集在一起，推动实地工作， 新的调查人员到该地区，通过丰富各级学员（本科生，研究生， 医学院），并提供试点和可行性赠款，高度有前途的创新项目的初级 investigators. CHSCC的组织和活动建立在现有的NIDDK资助的中心， 卓越的分子血液学为哈佛医学院社区和研究人员提供服务 在其他地方15年。由于现有的中心是哈佛医学区唯一的同类设施， 是良性血液学研究的焦点，也是培训下一代血液学专家的场所。 investigators. CHSCC的成员来自哈佛医学院的附属机构， 通过与BCH和Brigham & Women's Hospital的T32血液学培训项目的互动， (BWH)哈佛T32输血医学培训项目，以及哈佛干细胞研究所 （HSCI）。CHSCC由三个核心组成，其中两个核心集中在主要的动物模型上， 血液学研究，小鼠（核心A）和斑马鱼（核心B）。专注于这两个系统， 这两种方法的优点是，同时提供并行的发育和遗传研究的协同作用的好处。 这些核心为工程小鼠/斑马鱼的产生提供了最先进的服务，保持了关键的 这些菌株用于核心的日常工作，并分发给其他地方的研究人员， 和导出方法。此外，这些核心积极开发或整合新的 包括最近开发的用于基因组编辑的CRISPR/cas9技术。另外这些 核心是积极的人类血液疾病的模型，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，CORE C，提供人类iPS细胞 重编程，CRISPR/Cas9用于人类疾病建模，以及CRISPR/Cas9方法的咨询 编辑小鼠和斑马鱼，以及允许表征的按服务收费的流式细胞术核心 和分离造血细胞群体。总的来说，这三个核心为调查人员提供了国家- 最先进的血液学和疾病方法，并支持创新和疾病相关的研究， 将带来新的治疗策略除了这些核心之外，CHSCC还有一个管理核心， 管理与核心的通信，向研究者展示CHSCC的能力， 监督浓缩和试点及可行性计划。丰富的内容包括许多 中心成员和学员在成员实验室的教育机会， 大学本科生暑期课程试点和可行性计划以前支持创新， 初级研究人员的有前途的项目，希望这些资金将允许获得初步数据 申请NIH R 01或类似的奖项。作为一个CHSCC，现有的NIDDK资助的中心的影响， 卓越可以扩大到促进和支持良性血液学研究以外的成员 中心本身。我们相信BCH的CHSCC将成为血液学研究的国家资源。

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.