A CENTER OF MOLECULAR HEMATOLOGY

分子血液学中心

• 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
• 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

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.

项目摘要/摘要 在此申请中，波士顿的NIDDK合作血液学专业中心（CHSCC） 儿童医院（BCH），我们寻求通过提供关键来支持良性血液学研究领域 通过将互动成员汇集在一起​​，这些成员将向调查人员提供资源，这些成员将向前进并招募该领域 通过丰富各级学员的环境（本科生，毕业生， 医学院），并通过提供高度有希望的初级创新项目的飞行员和可行性赠款 调查人员。 CHSCC的组织和活动建立在现有的NIDDK资助的中心 为哈佛医学院社区和调查人员服务的分子血液学卓越 在其他地方持续了15年。由于现有的中心是哈佛医疗区的同类唯一设施，因此 代表了良性血液学研究的焦点，也是训练下一代的部位 调查人员。 CHSCC在哈佛医学院的附属机构中有成员，并且 与BCH和BRIGHAM＆妇女医院的T32血液学培训计划相互作用丰富 （BWH）和哈佛T32输血医学培训计划以及哈佛干细胞研究所 （HSCI）。 CHSCC由三个核心组成，其中两个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）。专注于这两个系统利用 每种的优势，同时从平行的发展和遗传研究中提供协同作用。 这些核心为工程老鼠/斑马鱼的产生提供最先进的服务，保持关键 在核心日常工作中使用并分配给其他地方的调查人员的菌株 和通过教授中心成员的出口方法。此外，这些核心积极发展或纳入新的核心 方法，包括最近开发的CRISPR/CAS9技术用于基因组编辑。另外，这些 核心积极生成人类血液学疾病模型，并鼓励翻译的努力 从这些动物模型到人类的知识。新的第三核Core C提供了人类IPS单元 重新编程，CRISPR/CAS9用于人类疾病建模，并就CRISPR/CAS9的方法进行咨询 鼠标和斑马鱼的编辑以及允许表征的费用流式细胞仪核心 和造血细胞群体的分离。总体上，这三个核心为调查人员提供了国家 - 血液学和疾病的艺术方法，并支持与创新和疾病相关的研究 将导致新的治疗策略。除这些核心外，CHSCC还有一个行政核心 管理与核心的通信，将CHSCC的功能宣传给调查人员，并 监督丰富和飞行员和可行性计划。丰富计划包括许多 成员实验室中的中心成员和学员的教育机会和活跃的 大学本科夏季课程。飞行员与可行性计划以前支持创新， 初级调查人员的有前途的项目，希望这些资金允许获得初步数据 用于NIH R01申请或类似奖励。作为CHSCC，现有的NIDDK资助中心的影响 卓越可以扩展以促进和支持良性血液学研究以外的成员 中心本身。我们认为，BCH的CHSCC将构成血液学研究的国家资源。

项目成果

Nonintegrating Human Somatic Cell Reprogramming Methods.

• DOI: 10.1007/10_2017_29
• 发表时间: 2018
• 期刊: Advances in biochemical engineering/biotechnology
• 作者: T. Schlaeger

The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells.

• DOI: 10.1038/ni.3644
• 发表时间: 2017-02
• 期刊: Nature immunology
• 影响因子: 30.5
• 作者: Beyaz S;Kim JH;Pinello L;Xifaras ME;Hu Y;Huang J;Kerenyi MA;Das PP;Barnitz RA;Herault A;Dogum R;Haining WN;Yilmaz ÖH;Passegue E;Yuan GC;Orkin SH;Winau F
• 通讯作者: Winau F

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: 10.1002/cpsc.103
• 发表时间: 2020
• 期刊: Current protocols in stem cell biology
• 作者: Skorik,Christian;Mullin,NathanielK;Shi,Michael;Zhang,Yosra;Hunter,Phoebe;Tang,Yang;Hilton,Brianna;Schlaeger,ThorstenM
• 通讯作者: Schlaeger,ThorstenM

Engineering Hematopoietic Stem Cells: Lessons from Development.

• DOI: 10.1016/j.stem.2016.05.016
• 发表时间: 2016-06-02
• 期刊: Cell stem cell
• 影响因子: 23.9
• 作者: Rowe RG;Mandelbaum J;Zon LI;Daley GQ
• 通讯作者: Daley GQ

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

• DOI: 10.1002/stem.2627
• 发表时间: 2017-07
• 期刊: Stem cells (Dayton, Ohio)
• 作者: Xie Y;Koch ML;Zhang X;Hamblen MJ;Godinho FJ;Fujiwara Y;Xie H;Klusmann JH;Orkin SH;Li Z
• 通讯作者: Li Z