Cancer Metabolism Core

癌症代谢核心

• 批准号: 10518246
• 负责人: Pankaj Kumar Singh
• 金额: $ 9.64万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10518246
• 关键词: Address; Biological Assay; Carbon; Cell Line; Cells; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Communication; Community Networks; Complex; Coupled; Data Analyses; Data Scientist; Dependence; Drug Kinetics; Ensure; Gas Chromatography; Gas-Liquid Chromatography; Genomic Library; Genus Hippocampus; Goals; Human; Information Dissemination; Infrastructure; Intercellular Fluid; Investigation; Kinetics; Label; Leadership; Libraries; Liquid Chromatography; Malignant neoplasm of pancreas; Mass Spectrum Analysis; Measures; Mediator of activation protein; Medical center; Metabolic; Metabolic Pathway; Metabolism; Methods; Mus; Nebraska; Organoids; Oxygen Consumption; Pancreatic Ductal Adenocarcinoma; Patients; Pharmaceutical Preparations; Pharmacodynamics; Physiological; Publications; Publishing; Quality Control; Research Personnel; Resistance; Sampling; Services; Signal Transduction; Specimen; Stable Isotope Labeling; Statistical Methods; Stromal Neoplasm; Testing; Tissues; Training; Tumor Tissue; Universities; Work; base; cancer cell; chemotherapy; cost effective; data management; design; effective therapy; exosome; experimental study; extracellular; follow-up; genetic manipulation; human tissue; improved; innovation; large scale data; lipidomics; member; metabolomics; neoplastic cell; novel; novel therapeutics; online resource; patient prognosis; programs; screening; stable isotope; tandem mass spectrometry; therapy resistant; three dimensional cell culture; tumor; tumor metabolism; whole genome

METABOLISM CORE Abstract The metabolism core of the proposed the UNMC Acquired Resistance to Therapy Network (ARTNet) Center for Pancreatic Cancer (ACPC) will study innovative, hypothesis-driven mechanisms of metabolic and signaling alterations that contribute to acquired therapy resistance in pancreatic ductal adenocarcinoma (PDAC). The core services provided by the metabolism core will be well integrated into all the three projects. The core will offer cost-effective metabolomics and data analysis support with appropriate quality controls for all projects by providing a centralized infrastructure and expertise in metabolomics, physiological assays, and metabolic dependency/vulnerability screens. The metabolism core will have three specific aims. The basic capabilities offered by the Core will include steady-state polar metabolomics and lipidomics (Specific Aim 1), Stable Isotope Resolved Metabolomics (SIRM) with kinetic flux analysis (Specific Aim 2), and Seahorse extracellular flux analyzer-based assays, fluorescent assays to investigate the metabolic state of cells, and identifying metabolic vulnerabilities (Specific Aim 3). The Metabolism Core will participate in the design and conduct of steady-state polar metabolomics, lipidomics, 13C-metabolite labeled kinetic flux analysis with cell lines, organoids, and exosomes. The core will also perform steady-state polar metabolomics and lipidomics for mouse and human tumor tissue specimens in all the projects. The core will also provide hands-on training, as needed, for the ACPC, other ARTNet centers, and other investigators. The core will also provide support for measuring drug concentrations and metabolism in the tissues and drug pharmacokinetics/ pharmacodynamics studies.

代谢核心 摘要 拟议的UNMC获得性耐药治疗网络（ARTNet）中心的代谢核心， 胰腺癌（ACPC）将研究创新的，假设驱动的代谢和信号传导机制 导致胰腺导管腺癌（PDAC）获得性耐药的改变。核心 代谢核心提供的服务将很好地融入所有三个项目。核心将提供 为所有项目提供具有成本效益的代谢组学和数据分析支持，并进行适当的质量控制， 提供代谢组学、生理分析和代谢分析方面的集中基础设施和专业知识， 依赖/漏洞屏幕。新陈代谢核心将有三个具体目标。基础能力 核心提供的技术将包括稳态极性代谢组学和脂质组学（具体目标1），稳定同位素 解析代谢组学（SIRM）与动力学通量分析（特定目标2）和海马细胞外通量 基于分析仪的测定、研究细胞代谢状态的荧光测定，以及鉴定代谢产物的方法。 具体目标3（Specific Aim 3）代谢中心将参与稳态的设计和实施 极性代谢组学、脂质组学、13 C-代谢物标记的细胞系动力学通量分析、类器官和 外来体。该核心还将为小鼠和人类进行稳态极性代谢组学和脂质组学研究 所有项目的肿瘤组织标本。该核心还将根据需要为ACPC提供实践培训， 其他ARTNet中心和其他研究人员。核心还将为测量药物提供支持。 组织中的浓度和代谢以及药物药代动力学/药效学研究。