Hematopoietic stem and progenitor cell regulation for enhanced clinical efficacy

 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，他们的工作高度依赖于本申请中建议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细胞(HSC)和祖细胞(HPC)水平上调节人类和小鼠的造血。该中心成员的研究目标是利用造血系统的不同成分来提高基于HSC/HPC的治疗的临床实用性和有效性。我们认为，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体外和体内造血干细胞行为的基本生物学过程，并最终建立将这些发现转化为转化努力的临床试验。建议中的CHSCC成员来自一组资金雄厚的研究人员，他们在实验和临床干细胞移植、HSC和HPC的信号传递和调控、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、新鲜分离的和体外操作的HSC的功能调节以及HSC暴露于电离辐射后的功能状态等方面具有不同但互为补充的经验。在这份CHSCC提交的文件中建议的核心是从现有的共享设施演变而来的，并已适应本计划的当前需求。这些资源包括：实验小鼠资源、光学显微镜、血管生成和流式细胞术核心。所有核心将支持作为CHSCC使命的基础和翻译研究，并将促进将新发现发展为人体试验。该计划还包括一个试点和可行性项目，部分由机构基金提供资金，以加强对年轻调查人员的培训，并增强他们成功竞争外部资金(如NIH)的能力。此外，为了确保持续的科学发展和进步，拟建的中心有一个完善的丰富计划，以促进年轻和成熟的CHSCC成员的发展。总而言之，CHSCC是一个重要的核心集合，需要促进和加强正在进行的基础和临床工作，并提供我们认为在未来五年需要的支持。

 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.