Hematopoietic stem and progenitor cell regulation for enhanced clinical efficacy

 描述（由申请人提供）：拟议的印第安纳州大学医学院（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提出的四个生物医学研究核心中的一个或多个。我们的CHSCC的中心主题是在造血干细胞（HSC）和祖细胞（HPC）水平上调节人和鼠的造血。该中心成员的研究目标是利用造血系统的不同组成部分，以提高基于HSC/HPC的治疗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。本申请中提议的CHSCC成员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的信号传导和调节、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、归巢和植入方面具有多样但互补的经验，调节新鲜分离和离体操作的HSC的功能，以及暴露于电离辐射后HSC的功能状态。本CHSCC提交文件中提出的堆芯是从现有的共享设施发展而来的，并已适应本计划的当前需求。这些包括：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CHSCC使命的基础和转化研究，并将促进新发现的人体试验开发。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，提高他们成功竞争校外（如NIH）资金的能力。此外，为了确保持续的科学增长和进步，拟议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。总之，CHSCC代表了促进和加强正在进行的基础和临床工作所需的关键核心的重要组合，并提供我们认为在未来五年内需要的支持。

 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.