Hematopoietic stem and progenitor cell regulation for enhanced clinical efficacy

中心项目总体总结 拟议中的印第安纳州大学医学院（IUSM）血液学卓越合作中心 （CCEH）汇集了25名研究人员，他们的研究活动集中在 非恶性血液学，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。我们的CCEH的中心主题是人类和 在造血干细胞（HSC）和祖细胞（HPC）水平的鼠造血。的目标 对该中心成员的调查是利用造血系统的不同组成部分， 改善基于HSC/HPC的疗法的临床实用性和功效的进展。我们相信在 为了达到这些目标，我们必须了解影响造血干细胞的基本生物学过程， 在基础科学实验室中进行体外和体内的行为，并最终建立临床试验， 将这些发现转化为成果。在这项申请中，建议的CCEH成员资格 来自一群非常富有成效，资金充足，以团队为导向的调查人员， 造血经验。这些经验包括实验和临床干细胞移植， HSC和HPC中的信号传导和调节，HSC与造血生态位之间的相互作用， HSC的动员、归巢和植入，新鲜分离的细胞在不同O2下的功能调节 水平和HSC的功能状态暴露于电离辐射后。本CCEH中提出的核心 提交内容是从先前资助期间建立的现有共享设施或核心演变而来的 期间，并专门定制，以满足CCEH成员和一般的当前研究需求 全国范围内的研究机构。这些包括：实验小鼠资源，流式细胞术和组织细胞术， 和缺氧核心所有核心将支持基础和转化研究，这些研究是我们的使命的基础。 CCEH和整个非恶性血液学研究社区。这些核心将促进 将新发现用于人体试验。此外，为了确保科学的持续发展， 为了取得进展，拟议中的中心有一个完善的浓缩计划，以促进两者的发展 青年和建立CCEH成员内外IUSM。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，并提供支持和 丰富的环境，以促进年轻和新的研究人员在非恶性肿瘤的成长和发展 血液学正如所提议的那样，CCEH代表了关键核心、基础设施和 研究人员需要促进和加强非恶性肿瘤的基础和临床工作， 血液学，并提供我们认为在未来五年内需要的支持。

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.