Hematopoietic stem and progenitor cell regulation for enhanced clinical efficacy

造血干细胞和祖细胞调节以增强临床疗效

• 批准号: 10201069
• 负责人: HAL E. BROXMEYER
• 金额: $ 23.95万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10201069
• 关键词: Advanced Development; Affect; Area; Basic Science; Biological Process; Biomedical Research; Bone Marrow Diseases; Cell Cycle Regulation; Cell Transplantation; Cells; Cellular biology; Clinic; Clinical; Clinical Investigator; Clinical Trials; Core Facility; Development; Disease; Elements; Ensure; Environment; Epigenetic Process; Exposure to; Extramural Activities; Flow Cytometry; Fostering; Funding; Funding Agency; Funding Mechanisms; Gene Transfer; Goals; Growth; Growth and Development function; Health Benefit; Hematology; Hematopoiesis; Hematopoietic; Hematopoietic System; Hematopoietic stem cells; Hereditary Disease; Homing; Human; In Vitro; Incubators; Indiana; Informal Social Control; Infrastructure; Institutes; Investigation; Ionizing radiation; Laboratories; Microscopy; Mission; Modality; Molecular; Molecular and Cellular Biology; Mus; Non-Malignant; Optics; Productivity; Publications; Publishing; Regulation; Research; Research Activity; Research Personnel; Resources; STEM research; Scientist; Secure; Seminal; Services; Signal Transduction; Stem cell transplant; Technology; Training; Translations; Transplantation; United States National Institutes of Health; Universities; Work; angiogenesis; base; career; cell behavior; clinical efficacy; cost; environmental enrichment for laboratory animals; experience; fetal; functional status; gene therapy; genetic approach; hematopoietic cell transplantation; hematopoietic engraftment; improved; in vivo; interdisciplinary approach; medical schools; member; migration; operation; progenitor; programs; public health relevance; self-renewal; stem; stem cells; success; translational study

 DESCRIPTION (provided by applicant): The proposed Indiana University School of Medicine (IUSM) Cooperative Hematology Specialized Core Center (CHSCC) brings together 28 investigators whose research activities are focused on various aspects of nonmalignant hematology and whose work is highly dependent on one or more of the four biomedical research cores proposed in this application. The central theme of our CHSCC is the regulation of human and murine hematopoiesis at the level of hematopoietic stem (HSC) and progenitor (HPC) cells. The goal of the investigations of members of this center is to leverage different components of the hematopoietic system to improve the advancement of the clinical utility and efficacy of HSC/HPC-based therapies. We believe that in order to attain these goals, we must understand basic biological processes that affect hematopoietic stem cell behavior both in vitro and in vivo in a basic science laboratory and to eventually establish clinical trials that transfor these findings into translational efforts. The proposed CHSCC membership in this application draws from a group of well-funded investigators with a diverse but complementary experience in experimental and clinical stem cell transplantation, signaling in and regulation of HSC and HPC, developmental emergence of fetal hematopoiesis, gene transfer, interactions between HSC and the hematopoietic niche, mobilization, homing and engraftment of HSC, modulation of function of freshly isolated and ex vivo manipulated HSC, and functional status of HSC after exposure to ionizing radiation. The cores proposed in this CHSCC submission evolved from existing shared facilities and have been adapted to the current needs of this program. These include: Experimental Mouse Resources, Optical Microscopy, Angiogenesis, and Flow Cytometry cores. All cores will support the basic and translational studies that underlie the mission of the CHSCC and will facilitate development of new discoveries into human trials. The program also includes a Pilot and Feasibility Project to be funded in part through Institutional funds in order to enhanc the training of young investigators and enhance their ability to successfully compete for extramural (e.g. NIH) funding. Furthermore, to ensure continued scientific growth and progress, the proposed center has a well-developed enrichment program to advance the development of both young and established CHSCC members. Together, the CHSCC represents an important assembly of critical cores needed to promote and enhance the basic and clinical work in progress and to provide support that we believe is needed over the next five years.

 描述（由申请人提供）：拟议的印第安纳大学医学院 (IUSM) 合作血液学专业核心中心 (CHSCC) 汇集了 28 名研究人员，他们的研究活动集中在非恶性血液学的各个方面，其工作高度依赖于本申请中提出的四个生物医学研究核心中的一个或多个。我们 CHSCC 的中心主题是在造血干 (HSC) 和祖 (HPC) 细胞水平上调节人类和小鼠造血作用。该中心成员的研究目标是利用造血系统的不同组成部分来提高基于 HSC/HPC 的疗法的临床实用性和疗效。我们相信，为了实现这些目标，我们必须了解在基础科学实验室中影响造血干细胞体外和体内行为的基本生物过程，并最终建立将这些发现转化为转化努力的临床试验。本申请中拟议的 CHSCC 成员资格来自一组资金充足的研究人员，他们在实验和临床干细胞移植、HSC 和 HPC 的信号转导和调节、胎儿造血的发育出现、基因转移、HSC 与造血生态位之间的相互作用、HSC 的动员、归巢和植入、新鲜分离的和 HPC 的功能调节等方面拥有多样化但互补的经验。 离体操作 HSC，以及暴露于电离辐射后 HSC 的功能状态。本 CHSCC 提交文件中提出的核心是从现有的共享设施演变而来，并已适应该计划的当前需求。其中包括：实验小鼠资源、光学显微镜、血管生成和流式细胞术核心。所有核心都将支持基础研究和转化研究，这些研究是 CHSCC 使命的基础，并将促进新发现进入人体试验的发展。该计划还包括一个试点和可行性项目，部分由机构资金资助，以加强对年轻研究人员的培训，并提高他们成功竞争外部（例如 NIH）资金的能力。此外，为了确保持续的科学成长和进步，拟议的中心拥有完善的充实计划，以促进年轻和成熟的 CHSCC 会员的发展。 CHSCC 共同代表了促进和加强正在进行的基础和临床工作并提供我们认为未来五年所需的支持所需的关键核心的重要集合。