Hematopoietic stem and progenitor cell regulation for enhanced clinical efficacy

整体中心项目总结 印第安纳大学医学院(IUSM)血液学合作卓越中心 (CCEH)汇集了25名研究人员，他们的研究活动集中在 非恶性血液病，其工作高度依赖于三种生物医学中的一种或多种 本申请中提出的研究核心。我们CCEH的中心主题是对人类和 小鼠在造血干细胞(HSC)和祖细胞(HPC)水平上的造血。的目标是 该中心成员的调查是利用造血系统的不同成分来 提高以HSC/HPC为基础的治疗方法的临床实用性和疗效。我们相信，在 为了实现这些目标，我们必须了解影响造血干细胞的基本生物学过程。 在基础科学实验室的体外和体内行为，并最终建立临床试验， 将这些发现转化为翻译工作。此应用程序中建议的CCEH成员资格 来自一群工作效率非常高、资金充足、以团队为导向的调查人员，他们拥有多样化但互补性强的 有过造血方面的经验。这些经验包括实验性和临床干细胞移植， HSC和HPC的信号转导和调节，HSC和造血生态位之间的相互作用， 不同氧条件下HSC的动员、归巢和植入及对新鲜分离细胞功能的调节 电离辐射后HSC的水平和功能状态。CCEH中建议的核心 提交材料是从先前供资期间建立的现有共享设施或核心演变而来的 并专门为满足CCEH成员和一般研究人员的当前研究需要而量身定制 全国范围内的研究社区。其中包括：实验小鼠资源、流式细胞术和组织细胞术， 和低氧核心。所有核心将支持基础和翻译研究，这些研究是我们的使命的基础 CCEH和非恶性血液学研究社区。这些核心将促进 将新发现发展成人体试验。此外，为了确保持续的科学发展和 进展，拟议的中心有一个完善的浓缩计划，以促进这两个项目的发展 在IUSM内外的年轻和成熟的CCEH成员。我们的目标是建立、维护和 成功运营这三个最先进的生物医学核心设施，并提供支持性和 丰富环境促进青年新人在非恶性肿瘤领域的成长与发展 血液学。正如提议的那样，CCEH代表着关键核心、基础设施和 研究人员需要促进和加强正在进行的非恶性肿瘤的基础和临床工作 并提供我们认为未来五年需要的支持。

OVERALL CENTER PROJECT SUMMARY The proposed Indiana University School of Medicine (IUSM) Cooperative Center of Excellence in Hematology (CCEH) brings together 25 investigators whose research activities are focused on various aspects of nonmalignant hematology and whose work is highly dependent on one or more of the three biomedical research cores proposed in this application. The central theme of our CCEH 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 transform these findings into translational efforts. The proposed CCEH membership in this application draws from a group of very productive, well-funded and team-oriented investigators with a diverse but complementary experience in hematopoiesis. These experiences include experimental and clinical stem cell transplantation, signaling in and regulation of HSC and HPC, interactions between HSC and the hematopoietic niche, mobilization, homing and engraftment of HSC, modulation of function of freshly isolated cells under different O2 levels, and functional status of HSC after exposure to ionizing radiation. The cores proposed in this CCEH submission evolved from existing shared facilities or cores previously established during the prior funding period and were tailored specifically to meet the current research needs of CCEH members and the general research community nationwide. These include: Experimental Mouse Resources, Flow and Tissue Cytometry, and Hypoxia cores. All cores will support the basic and translational studies that underlie the mission of our CCEH and the community of nonmalignant hematology research at large. These cores will facilitate the development of new discoveries into human trials. 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 CCEH members inside and outside IUSM. Our goal is to establish, maintain, and successfully operate these three state-of-the-art biomedical core facilities and to provide a supportive and enriching environment to foster the growth and development of young and new investigators in nonmalignant hematology. As proposed, the CCEH represents an important assembly of critical cores, infrastructure, and investigators needed to promote and enhance the basic and clinical work in progress in nonmalignant hematology and to provide support that we believe is needed over the next five years.