Metabolomics Core

代谢组学核心

• 批准号: 10441576
• 负责人: Costas Andreas Lyssiotis
• 金额: $ 25.62万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10441576
• 关键词: Address; Allogenic; Amino Acids; Bile Acids; Bioenergetics; Bioinformatics; Biological Assay; Biostatistics Core; Blood specimen; Butyrates; Carbohydrates; Carbon; Cells; Clinical Trials; Custom; Data; Data Analyses; Data Collection; Development; Disease; Enrollment; Ensure; Epithelial; Epithelial Cells; Feces; Gastrointestinal tract structure; Genetic Diseases; Genus Hippocampus; Glucose; Gnotobiotic; Graph; Hematopoietic Neoplasms; Hematopoietic Stem Cell Transplantation; Human; Incidence; Informatics; Label; Laboratories; Maintenance; Malignant Neoplasms; Mass Spectrum Analysis; Measures; Metabolic; Metabolic Pathway; Metabolism; Methodology; Methods; Morbidity - disease rate; Mus; Nature; Nitrogen; Nutrient; Organism; Pathway interactions; Patients; Pharmaceutical Preparations; Plasma; Population; Production; Program Research Project Grants; Property; Research Project Grants; Research Proposals; Research Support; Resources; Safety; Severities; Starch; Statistical Data Interpretation; Technology; Therapeutic; Tissues; Toxic effect; Tracer; Volatile Fatty Acids; assay development; base; bile acid metabolism; chronic infection; experience; gastrointestinal; graft vs host disease; gut microbiome; host microbiome; in vivo Model; insight; large datasets; lipidome; metabolome; metabolomics; microbial; microbial community; microbiome; microbiome analysis; nutrient metabolism; pharmacodynamic biomarker; prevent; programs; stable isotope; stool sample; uptake

PROJECT SUMMARY/ABSTRACT – CORE B Allogenic hematopoietic stem cell transplant (allo-HCT) can provide a cure for chronic infections, genetic diseases, or cancers of the blood. However, its therapeutic utility is limited by associated toxicities resulting from graft versus host disease (GVHD). Among the most prominent morbidities of GVHD is damage to the gastrointestinal tract. Recent results from our groups have revealed that the severity of GVHD is impacted by the nature and metabolic properties of the gut microbiome. Further, we found that promotion of microbial communities that facilitate the metabolism of starch into butyrate and reprogram bile acid metabolism of the host ameliorate or even prevent GVDH following BMT. The measure and quantitation of metabolism is essential to address the associated experimental aims across the research proposals. The purpose of the Metabolomics core is to support the research projects that build on these studies to detect and quantify metabolites from these pathways in stool from mice, bacterial populations, human epithelial cells, and longitudinal stool samples of patients in the associated clinical trial. Further, this core will also provide global insights into host and microbiome metabolism using stable isotope tracing technologies and untargeted metabolome-wide profiling. By centralizing the development, maintenance, and implementation of metabolomics methods, this core will provide state-of-the-art capabilities to facilitate data collection and analysis while ensuring consistency across projects.

项目总结/摘要-核心B 异基因造血干细胞移植（allo-HCT）可以治疗慢性感染、遗传性疾病和其他疾病。 疾病或血液癌症。然而，其治疗效用受到相关毒性的限制 由移植物抗宿主病（GVHD）引起。GVHD最突出的发病率之一是 对胃肠道的损害。我们小组最近的结果显示， GVHD受肠道微生物组的性质和代谢特性的影响。此外，我们发现， 促进微生物群落，促进淀粉代谢为丁酸和重编程 宿主的胆汁酸代谢改善甚至预防BMT后的GVDH。的措施和 代谢的定量对于解决跨学科的相关实验目标至关重要。 研究提案。代谢组学核心的目的是支持研究项目， 在这些研究的基础上，检测和定量小鼠粪便中这些途径的代谢物，细菌 在相关的临床试验中，患者的群体、人上皮细胞和纵向粪便样品被检测。 审判此外，该核心还将使用稳定的微生物代谢提供对宿主和微生物组代谢的全球见解。 同位素示踪技术和非靶向代谢组范围分析。通过集中开发， 维护和代谢组学方法的实施，这一核心将提供最先进的 能力，以促进数据收集和分析，同时确保跨项目的一致性。