Center for Iron and Heme Disorders (CIHD)

铁和血红素疾病中心 (CIHD)

• 批准号: 10201103
• 负责人: John Dearborn Phillips
• 金额: $ 23.95万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-05 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10201103
• 关键词: Anemia; Assisted Living Facilities; Basic Science; Binding; Biochemical; Biological; Biological Assay; Biological Process; Biomedical Research; Cell Respiration; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chemicals; Clinical Research; Clustered Regularly Interspaced Short Palindromic Repeats; Communities; Cultured Cells; DNA biosynthesis; Detection; Disease; Enzymes; Equipment; Fees; Funding; Gene Mutation; Gene-Modified; Generations; Genes; Genetic; Genome engineering; Goals; Hematology; Hematopoiesis; Heme; Hemeproteins; Hemoglobin; Homeostasis; Human; Individual; Institution; Iron; Iron Overload; Liquid substance; Metabolic Pathway; Metabolism; Metals; Molecular; Mutation; National Institute of Diabetes and Digestive and Kidney Diseases; Non-Malignant; Phenotype; Pilot Projects; Play; Porphyrias; Porphyrins; Proteins; Reagent; Research Activity; Research Design; Research Personnel; Research Project Grants; Resources; Role; Services; Technology; Training; Transition Elements; Universities; Utah; Zebrafish; design; gene discovery; genome editing; heme biosynthesis; human disease; medical schools; member; metabolomics; metal metabolism disorder; next generation; novel strategies; operation; oxygen transport; programs; stem; transcription activator-like effector nucleases

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.

项目摘要： 拟议的犹他州大学医学院（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方面： 铁和血红素代谢和非恶性血液学。铁在许多生物学中起着重要作用。 这些过程包括血红素合成、氧运输、细胞呼吸和DNA合成。失调 无论是铁的缺乏还是过量，都会导致疾病。血红素是 血红素是血红蛋白和其他血红素蛋白的重要组成部分，但血红素也在许多代谢途径中起调节作用。 血红素生物合成的障碍是导致一组重要的人类疾病的原因，即 卟啉症拟议中的犹他州铁和血红素疾病中心（CIHD）将支持22 他们的研究项目集中在铁，卟啉和血红素在真核生物中的作用。 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，并已调整为 CIHD的需求。其中包括：突变生成和检测核心，它提供了尖端的 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 优化以产生具有基因发现和遗传和化学工程基因组的斑马鱼 代谢组学核心，提供代谢组学表型分析和分子鉴定;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。这些核心所提供的服务将使研究者能够：1） 确定基因在造血或铁超载中的作用; 2）确定基因修饰的影响， 在培养的细胞或生物流体中的代谢突变;和3）在生物化学水平上鉴定以下的影响： 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。的 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）和浓缩方案是 专为非恶性血液学领域的受训者和年轻研究人员以及高级研究人员设计。 希望进入这个领域的研究人员。委员会的22名成员分别来自香港中文大学及 犹他州和其他机构，一半的成员属于犹他州以外的机构。的目标 CIHD将成为研究铁和血红素的国家资源，并激励下一代 研究者关注铁、血红素和非恶性血液学。