Center for Iron & Heme Disorders at the University of Utah

项目概要： 拟议的犹他大学血液学卓越合作中心 (CCEH) 汇集了 38 研究活动集中于铁和血红素代谢以及非铁代谢的各个方面的研究人员 恶性血液学。铁在许多生物过程中发挥着重要作用，包括血红素合成、 氧气运输、细胞呼吸和 DNA 合成。铁稳态失调，要么来自 不足或过多，都会导致疾病。血红素是血红蛋白和其他血红蛋白的关键成分，但是 血红素还在许多代谢途径中发挥调节作用。血红素生物合成障碍是 造成一组重要的人类疾病，即卟啉症。犹他州钢铁中心 血红素疾病 (CIHD) 将支持由 38 名研究人员组成的研究基地的活动，他们的研究 项目重点关注铁、卟啉和血红素在真核代谢中的作用。中心活动 成员包括旨在确定疾病机制的基础和临床研究。为了完成 我们的目标是，我们提出一个行政核心和四个生物医学研究核心。大多数核心 已经存在并已进行调整以满足 CIHD 的需求。其中包括：铁和血红素 Core，可以测定和定量金属、卟啉、血红素生物合成酶以及铁结合和 其他蛋白质；代谢组学核心，提供代谢组表型分析和分子鉴定；一个 突变生成和检测核心，通过 CRISPR 和 TALEN试剂；以及本次更新中的一个新核心，即蛋白质-代谢物相互作用组学核心，它提供了 蛋白质组学服务，但增加了识别与蛋白质相互作用的代谢物的独特技术 并可能以新的方式对蛋白质进行翻译后修饰。这些核心提供的服务将使 个别研究人员：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体液代谢的影响； 3) 识别于 生化水平 影响各个水平的铁和血红素稳态的突变或条件的影响。 行政核心将为 CIHD 活动提供预算和科学指导。核心充值费用 将用于加强和扩大核心业务。强化计划是为学员和 非恶性血液学领域的年轻研究人员以及希望进入该领域的高级研究人员 场。该研究基地来自犹他大学和其他机构，其中一半 属于犹他州以外机构的成员。我们将研究基地从 22 个增加到 38 个 每年增加约 4 名研究人员。 CIHD 的目标是成为国家研究资源 涉及铁和血红素，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 Cooperative Centers of Excellence in Hematology (CCEH) brings together 38 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 Utah Center for Iron and Heme Disorders (CIHD) will support the activities of a Research Base of 38 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 an Administrative Core and four Biomedical Research Cores. The majority of the cores are already present and have been adjusted to meet the needs of the CIHD. These include: an Iron and Heme Core, which can assay and quantitate metals, porphyrins, heme biosynthetic enzymes and iron-binding and other proteins; a Metabolomics Core, which provides metabolomic phenotyping and molecular identification; a Mutation Generation and Detection Core, which provides cutting edge genome editing through CRISPR and TALEN reagents; and a new core in this renewal, the Protein-Metabolite Interactomics Core that provides proteomics services but adds the unique technology of identification of metabolites that interact with a protein and may post-translationally modify the protein in novel ways. 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 at the biochemical level the effect of mutations or conditions that affect iron and heme homeostasis on all levels. The Administrative Core will provide budgetary and scientific guidance to CIHD activities. Core recharge fees will be used to enhance and expand core operations. An Enrichment Program is designed for trainees and young investigators in the fields of nonmalignant hematology and for senior investigators who wish to enter this field. The Research Base is drawn from both the University of Utah and other institutions, with half of the members belonging to institutions outside of Utah. We have increased the Research base from 22 to 38 with the addition of ~4 investigators each year. 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.