CORE CENTERS OF EXCELLENCE IN MOLECULAR HEMATOLOGY

对多能性造血干细胞进行有效的遗传操作，可使骨髓源性细胞遗传性疾病中的突变表型得到功能纠正。我们计划的长期目标是在分子水平上理解和纠正影响多能造血干细胞来源的细胞的遗传疾病。我们认为，要实现这一目标，我们必须了解影响干细胞在体外和体内行为的基本生物学过程。拟议的中心成员来自一组资金充足的研究人员，他们在造血和干细胞生物学、逆转录病毒和AV介导的基因转移、分子遗传学、病毒学、骨髓移植和生殖学方面具有不同但互补的经验。该小组与NIH资助的跨越基础，转化和临床研究的项目高度合作和互动。在本次CCEMH提交中提出的核心都是由我们以前的分子血液学卓越中心资助的原始核心的更成熟版本（干细胞实验室、载体生产设施和小鼠核心）和这3个现有核心的扩展（细胞和分子生物学核心和基因治疗工作组/生物统计学核心）进一步支持血液学基础研究，利用干细胞和生长因子的转化血液学试验，以及将基因转移技术发展为转化试验。这两个新的核心是值得注意的，因为它们提供了严格进行人体试验的基础设施，同时定量评估转基因表达和生化终点，这是评估基因转移方案的关键组成部分。CCEMH共同代表了一个逻辑的核心组件，需要继续进行中的基本工作，并提供我们认为在未来5年内需要的支持。

The effective genetic manipulation of pluripotent, reconstituting hematopoietic stem cells should lead to function correction of the mutant phenotype in inherited disorders of bone marrow-derived cells. The long term goal of our program is to understand and correct at the molecular level, genetic diseases affecting cells derived from pluripotent hematopoietic stem cells. We believe that to attain this goal, we must understand basic biological processes that affect stem cell behavior both in vitro and in vivo. The proposed Center membership draws from a group of well-funded investigators with diverse but complementary experience in hematopoiesis and stem cells biology, retroviral- and AV-mediated gene transfer, molecular genetics, virology, bone marrow transplantation and neonatology. The group is highly collaborative and interactive with NIH-funded projects that span basic, translational and clinical research. The cores proposed in this CCEMH submission are both more mature versions of the original cores supported by our previous Centers of Excellence in Molecular Hematology grant (Stem Cell Laboratory, Vector Production Facility and Mouse Core) and extensions of these 3 existing cores (Cell and Molecular Biology Core and Gene Therapy Working Group/Biostatistics Core) to further support hematology basic research, translational hematology trials utilizing stem cells and growth factors, and the development of gene transfer technology into translational trials. These two new cores are noteworthy, as they provide the infrastructure to rigorously perform human trials, while assessing quantitatively transgene expression and biochemical endpoints, a critical component in the evaluation of gene transfer protocols. Together the CCEMH represent a logical assembly of cores needed to continue the basic work in progress and to put in place support which we believe will be needed over the next 5 years.