Center for Iron and Heme Disorders (CIHD)

项目总结： 建议的犹他大学医学院(UUSM)合作血液学专业核心 中心(CHSCC)汇集了22名研究人员，他们的研究活动集中在以下各个方面 铁和血红素代谢与非恶性血液病。铁在许多生物中扮演着重要的角色 包括血红素合成、氧运输、细胞呼吸和DNA合成的过程。监管不力 铁的动态平衡，无论是由于缺乏还是过量，都会导致疾病。亚铁血红素是 血红蛋白和其他血红素蛋白，但血红素也在许多代谢途径中起着调节作用。 血红素生物合成障碍是导致人类一组重要疾病的原因，即 卟啉症。拟议的犹他州铁和血红素紊乱中心(CIHD)将支持22个 研究项目集中在铁、卟啉和血红素在真核生物中的作用的研究人员 新陈代谢。中心成员的活动包括基础和临床研究，旨在确定 疾病机制。为了实现我们的目标，我们建议提供一个管理核心和四个 生物医学研究核心。大多数核心已经存在，并已调整到 CIHD的需求。其中包括：突变生成和检测核心，可提供尖端技术 通过CRISPR和TALEN试剂进行基因组编辑；斑马鱼核心，其中的条件已经 为基因发现和遗传和化学方面的基因工程基因组产生斑马鱼进行了优化 筛选；代谢组学核心，提供代谢组表型和分子鉴定；以及 铁和血红素核心，可以分析和定量金属，卟啉，血红素生物合成酶和 铁结合蛋白和其他蛋白质。这些核心提供的服务将使个人调查员能够：1) 确定基因在造血或铁超载中的作用；2)确定基因修饰或 突变对培养细胞或生物液代谢的影响；以及3)在生化水平上确定 从基因到蛋白质再到产物的水平上对血红素合成的突变或治疗。这个 行政核心将为CIHD活动提供预算和科学指导。核心充值费用将 用于增强和扩展核心业务。试点和可行性(P&F)和浓缩计划是 专为非恶性血液学领域的实习生和年轻研究人员以及高级研究人员设计 希望进入这一领域的调查人员。CIHD的22名成员都来自加州大学 犹他州和其他机构，一半的成员属于犹他州以外的机构。世界银行的目标是 CIHD将成为有关铁和血红素研究的全国性资源，并激励下一代 研究人员专注于铁、血红素和非恶性血液学。

Project Summary: The proposed University of Utah School of Medicine (UUSM) Cooperative Hematology Specialized Core Center (CHSCC) brings together 22 investigators whose research activities are focused on various aspects of iron and heme metabolism and non-malignant hematology. Iron plays an essential role in many biological processes including heme synthesis, oxygen transport, cellular respiration and DNA synthesis. Malregulation of iron homeostasis, either from deficiency or excess, results in disease. Heme is a key component of hemoglobin and other hemoproteins, but heme also plays a regulatory role in a number of metabolic pathways. Disorders of heme biosynthesis are responsible for an important group of human diseases, namely the porphyrias. The proposed Utah Center for Iron and Heme Disorders (CIHD) will support the activities of 22 investigators whose research projects focus on the roles of iron, porphyrins and heme in eukaryotic metabolism. The activities of center members encompass both basic and clinical studies designed to identify disease mechanisms. To accomplish our goals, we propose to provide an Administrative Core and four Biomedical Research Cores. The majority of the cores are already present and have been adjusted to the needs of the CIHD. These include: a Mutation Generation and Detection Core, which provides cutting edge genome editing through CRISPR and TALEN reagents; a Zebrafish Core, in which conditions have been optimized to generate zebrafish with engineered genomes for both gene discovery and genetic and chemical screens; a Metabolomics Core, which provides metabolomic phenotyping and molecular identification; and an Iron and Heme Core, which can assay and quantitate metals, porphyrins, heme biosynthetic enzymes and iron-binding and other proteins. The services provided by these cores will enable individual investigators to: 1) identify the role of genes in hematopoiesis or iron overload; 2) determine the effects of gene modification or mutations on metabolism in cultured cells or biological fluids; and 3) identify on a biochemical level the effect of mutations or treatments on heme synthesis on levels ranging from gene to protein to products. The Administrative Core will provide budgetary and scientific guidance to CIHD activities. Core recharge fees will be used to enhance and expand Core operations. The Pilot & Feasibility (P&F) and Enrichment Programs are designed for trainees and young investigators in the fields of nonmalignant hematology and for senior investigators who wish to enter this field. The 22 members of the CIHD are drawn from both the University of Utah and other institutions, with half of the members belonging to institutions outside of Utah. The goals of the CIHD are to be a national resource for studies involving iron and heme and to inspire the next generation of investigators focused on iron, heme and nonmalignant hematology.