Core Center for Stem Cell and Transplantation Biology

 描述(由申请人提供)：本申请建议从P30血液学卓越核心中心(DK056465-16)过渡到NIDDK赞助的U54合作血液学专业核心中心(CHSCC)。这一过渡将促进国家一级的合作、培训和资源共享。CHSCC的目标是推进干细胞和移植生物学的研究，从而加速新疗法的开发。这需要能够预见和满足不断发展的研究基础的资源。我们过去的经验表明，如果能够接触到关键的细胞、技术和专业知识，就可以在这一研究领域招募新的调查人员 以合理的价格。为了满足这些需求，我们提议提供一个行政核心和五个生物医学研究核心。这些措施包括：细胞采购和处理，以提供大量纯化的正常造血干、祖细胞和基质细胞，这些细胞来自成人血液和骨髓以及脐带血和诱导的多能干细胞(IPSC)；载体生产，提供Lenti、Retro、泡沫和腺相关病毒载体，用于基因转导、标记和编辑；专门的小鼠服务，包括体内异种移植试验和生成定制的转基因模型；犬大动物模型，用于临床前研究，包括协议的制定和IACUC的批准；以及分子文库开发和筛选，提供对CRISPR基因组编辑和shRNA文库的访问。这些中心提供的服务将使个人研究人员能够：1)分离和鉴定干细胞/祖细胞，2)从基因上标记、编辑或以其他方式改变它们的基因表达，3)在体外和体内准确检测和定量它们的后代，以及4)在分子、细胞和整个动物水平上确定这些操作对造血的影响。行政核心提供对所有CHSCC活动的预算和科学监督，并管理一个收费系统以产生计划收入。计划收入用于加强和扩大核心业务，以及支持为CHSCC网络中的受训人员和年轻研究人员设计的试点和可行性(P&F)和充实计划。最后，管理核心将与Sage Bionetworks合作，创建一个可公开搜索的数据档案，将调查人员与通过CHSCC计划生成的注释数据、技术和协议联系起来。该CHSCC的30名成员研究基地每年收到2900多万与非恶性血液病相关的研究的直接费用，其中380万直接来自NIDDK。

 DESCRIPTION (provided by applicant): This application proposes a transition from a P30 Core Center of Excellence in Hematology (DK056465-16) to an NIDDK-sponsored U54 Cooperative Hematology Specialized Core Center (CHSCC). This transition will facilitate collaborations, training, and resource sharing on a national level. The goal of this CHSCC is to advance research in stem cell and transplantation biology and thereby accelerate the development of new therapies. This requires resources that anticipate and meet the needs of an ever evolving research base. Our past experience has shown that new investigators can be recruited into this area of research if critical cells, technologies, and expertise can be accessed at reasonable cost. To address these needs we are proposing to provide an Administrative Core and five biomedical research cores. These include Cell Procurement and Processing, to provide large quantities of purified normal hematopoietic stem, progenitor, and stromal populations harvested from adult blood and marrow as well as cord blood and induced pluripotent stem cells (iPSC); Vector Production to provide lenti, retro, foamy and adeno-associated virus vectors for gene transduction, marking, and editing; Specialized Mouse Services including in vivo xenogeneic transplantation assays and the generation of custom transgenic models; the Canine Large Animal Model for preclinical studies including protocol development and IACUC approval; and Molecular Library Development and Screening, that provides access to CRISPR genome editing and shRNA libraries. The services provided by these cores will enable individual investigators to: 1) isolate and characterize stem/progenitor cells, 2) genetically mark, edit or otherwise alter their gene expression, 3) accurately detect and quantitate their progeny in vitro and in vivo, and 4) determine the effects of these manipulations on hematopoiesis at the molecular, cellular, and whole animal levels. The Administrative Core provides budgetary and scientific oversight of all CHSCC activities, and manages a charge back system to generate program income. Program income is used to enhance and expand Core operations as well as support the Pilot & Feasibility (P&F) and Enrichment programs designed for trainees and young investigators in the CHSCC network. Finally, the Administrative Core will work with Sage Bionetworks to create a publicly searchable data archive linking investigators to annotated data, techniques, and protocols generated through the CHSCC programs. The 30 member research base of this CHSCC receives more than 29 million/year direct costs in non-malignant Hematology-related research, 3.8 million comes directly from the NIDDK.