A CENTER OF MOLECULAR HEMATOLOGY

分子血液学中心

基本信息

批准号：
10201083
负责人：
STUART H ORKIN
金额：
$ 23.95万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-05 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10201083
关键词：
Affect Animal Model Animals Area Award Benign Blood Blood Cells Boston CRISPR/Cas technology Cells Communication Communities Consultations Data Development Disease Disease model Educational Activities Engineering Fee-for-Service Plans Fishes Flow Cytometry Fostering Funding Gene-Modified Generations Genes Genetic study Goals Grant Hematological Disease Hematology Hematopoiesis Hematopoietic Hospitals Human Institutes Institution Knowledge Laboratories Medical Methods Molecular Mus National Institute of Diabetes and Digestive and Kidney Diseases Patients Pediatric Hospitals Population Reagent Research Research Personnel Research Project Grants Resources Services Site System Teaching Method Technology Training Training Programs Translating United States National Institutes of Health Woman Work Zebrafish college developmental genetics environmental enrichment for laboratory animals experience fundamental research genome editing human disease human model human stem cells improved induced pluripotent stem cell innovation medical schools member molecular hematology new technology next generation novel strategies novel therapeutic intervention novel therapeutics programs recruit service member stem cells summer program synergism transfusion medicine translational study undergraduate student

项目摘要

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.

项目概要/摘要在这份针对波士顿 NIDDK 合作血液学专业核心中心 (CHSCC) 的申请中儿童医院 (BCH)，我们寻求通过提供关键的支持良性血液学研究领域为调查人员提供资源，通过聚集互动成员来推动该领域的发展并招募通过丰富各个级别（本科生、研究生、医学院），并为初级学生的极具前景的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 NIDDK 资助的现有中心的基础上为哈佛医学院社区和研究人员提供卓越的分子血液学服务在其他地方工作了15年。由于现有中心是哈佛医学区唯一的此类设施，因此代表良性血液学研究的焦点和下一代的培训场所调查人员。 CHSCC 的成员来自哈佛医学院的附属机构，通过与 BCH 和布莱根妇女医院的 T32 血液学培训项目的互动而丰富 (BWH) 和哈佛 T32 输血医学培训计划以及哈佛干细胞研究所（恒生综合指数）。 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，小鼠（核心 A）和斑马鱼（核心 B）。专注于这两个系统可以利用各自的优点，同时提供并行发育和遗传研究的协同效益。这些核心为工程小鼠/斑马鱼的生成提供最先进的服务，维持关键的核心日常工作中使用的菌株，并分发给其他地方的研究人员，以及教学中心成员的导出方法。此外，这些核心还积极开发或整合新的方法，包括最近开发的用于基因组编辑的 CRISPR/cas9 技术。此外，这些核心积极致力于生成人类血液疾病模型并鼓励努力转化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、用于人类疾病建模的 CRISPR/Cas9 以及 CRISPR/Cas9 方法咨询小鼠和斑马鱼的编辑，以及可进行表征的收费流式细胞术核心和造血细胞群的分离。总的来说，这三个核心为调查人员提供了状态- 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导致新的治疗策略。除了这些核心之外，CHSCC 还有一个行政核心：管理与核心的通信，向调查人员宣传 CHSCC 的功能，以及监督丰富、试点和可行性计划。强化计划包括许多为中心成员和受训者提供在成员实验室和积极的教育机会大学本科生暑期课程。试点和可行性计划此前曾支持创新、初级研究人员有前途的项目，希望这些资金能够获得初步数据 NIH R01 申请或类似奖项。作为 CHSCC，现有 NIDDK 资助的中心的影响卓越可以扩展到促进和支持良性血液学研究，超越会员范围中心本身。我们相信 BCH 的 CHSCC 将成为国家血液学研究资源。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Reduced Erg Dosage Impairs Survival of Hematopoietic Stem and Progenitor Cells.

减少 Erg 剂量会损害造血干细胞和祖细胞的存活。

DOI：
发表时间：
2017-07
期刊：
影响因子：
0
作者：
Xie, Ying;Koch, Mia Lee;Zhang, Xin;Hamblen, Melanie J;Godinho, Frank J;Fujiwara, Yuko;Xie, Huafeng;Klusmann, Jan;Orkin, Stuart H;Li, Zhe
通讯作者：
Li, Zhe

Nonintegrating Human Somatic Cell Reprogramming Methods.

DOI：
10.1007/10_2017_29
发表时间：
2024-09-13
期刊：
Advances in biochemical engineering/biotechnology
影响因子：
0
作者：
T. Schlaeger
通讯作者：
T. Schlaeger

Slow phosphorylation of a tyrosine residue in LAT optimizes T cell ligand discrimination.

LAT 中酪氨酸残基的缓慢磷酸化优化了 T 细胞配体辨别能力。

DOI：
发表时间：
2019
期刊：
影响因子：
30.5
作者：
Lo, Wan;Shah, Neel H;Rubin, Sara A;Zhang, Weiguo;Horkova, Veronika;Fallahee, Ian R;Stepanek, Ondrej;Zon, Leonard I;Kuriyan, John;Weiss, Arthur
通讯作者：
Weiss, Arthur

Xeno-Free Reprogramming of Peripheral Blood Mononuclear Erythroblasts on Laminin-521.

外周血单核成红细胞在层粘连蛋白 521 上的无异源重编程。

DOI：
发表时间：
2020
期刊：
影响因子：
0
作者：
Skorik, Christian;Mullin, Nathaniel K;Shi, Michael;Zhang, Yosra;Hunter, Phoebe;Tang, Yang;Hilton, Brianna;Schlaeger, Thorsten M
通讯作者：
Schlaeger, Thorsten M

Tie2Cre-mediated gene ablation defines the stem-cell leukemia gene (SCL/tal1)-dependent window during hematopoietic stem-cell development.

Tie2Cre 介导的基因消融定义了造血干细胞发育过程中干细胞白血病基因 (SCL/tal1) 依赖的窗口。