Cancer Metabolism Core

癌症代谢核心

• 批准号: 10707540
• 负责人: Pankaj Kumar Singh
• 金额: $ 9.37万
• 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/10707540
• 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 Coordinating Center; Data Scientist; Dependence; Drug Kinetics; Ensure; Gas Chromatography; Genomic Library; Genus Hippocampus; Goals; Human; Information Dissemination; Infrastructure; Intercellular Fluid; Investigation; Kinetics; Label; Leadership; Libraries; Liquid Chromatography; Malignant neoplasm of pancreas; Mass Fragmentography; Mass Spectrum Analysis; Measures; Mediator; 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; cancer cell; chemotherapy; cost effective; 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 抽象的 提议的UNMC获得的对治疗网络（ARTNET）中心的代谢核心 胰腺癌（ACPC）将研究代谢和信号传导的创新，假设驱动的机制 导致胰腺导管腺癌（PDAC）中获得的治疗耐药性的改变。核心 代谢核心提供的服务将很好地整合到所有三个项目中。核心将提供 具有成本效益的代谢组学和数据分析支持，并通过适当的质量控制对所有项目进行适当的质量控制 提供代谢组学，生理测定和代谢方面的集中基础设施和专业知识 依赖性/漏洞屏幕。新陈代谢核心将具有三个具体目标。基本功能 核心提供的将包括稳态极性代谢组学和脂质组学（特定目标1），稳定的同位素 带有动力学通量分析（特定目标2）和海马细胞外通量的分解代谢组学（SIRM） 基于分析仪的测定法，荧光测定以研究细胞的代谢状态，并鉴定代谢 漏洞（特定目标3）。代谢核心将参与稳态的设计和行为 极性代谢组学，脂质组学，13C量代谢物标记了细胞系，类器官和细胞系的动力学分析 外泌体。核心还将对小鼠和人进行稳态的极性代谢组学和脂质组学 肿瘤组织在所有项目中标本。核心还将根据需要为ACPC提供动手培训 其他Artnet中心和其他调查人员。核心还将为测量药物提供支持 组织和药物药代动力学/药效学研究中的浓度和代谢。