Oxidative Lipidomics Core

氧化脂质组学核心

• 批准号: 8643333
• 负责人: Valerian E Kagan
• 金额: $ 20.13万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-03 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8643333
• 关键词: Acute Lung Injury; Adult Respiratory Distress Syndrome; Bacteria; Biochemical Pathway; Biological Markers; Cardiolipins; Cell membrane; Cells; Development; Goals; Image; Individual; Infection; Knowledge; Lipid Peroxidation; Lipids; Liquid Chromatography; Lung; Mass Spectrum Analysis; Mediator of activation protein; Metabolic Pathway; Mitochondria; Modality; Molecular; Pathogenesis; Performance; Phospholipids; Protocols documentation; Research Personnel; Sampling; Signal Transduction; Structure of parenchyma of lung; Techniques; Therapeutic; Thin Layer Chromatography; Toxin; Training; Work; base; design; innovation; instrumentation; novel; novel therapeutics; oxidation; oxidized lipid; peroxidation; research study; response

Currently, there is no effective pharmacologic therapy against ARDS because of insufficient knowledge of the pathogenesis mechanisms. The overarching focus of the P01 is on mechanisms of pulmonary responses to a new pulmonary toxin and regulator, the anionic phosholipid, cardiolipin (CL) originating from bacteria or mitochondria of damaged host cells during acute lung injury. Thus elucidation of novel metabolic and biochemical pathways of different molecular species of CL, its metabolites and their interactions with other pulmonary lipids and their peroxidation products are fundamental to all four projects of the P01. The Oxidative Lipidomics Core (Core B) has been designed to allow researchers in the projects to perform detailed analysis - identification, characterization and imaging - of all major molecular species of Cls, other different classes of lipids as well as their oxidation products. This will be achieved by using sophisticated state-of-the art techniques based on different versions of mass-spectrometry (MS) combined with liquid¿ chromatography (LC) or high-performance thin-layer chromatography (HPTLC) protocols. Specific Aims of the Oxidative Lipidomics Core B are to: 1. Provide professional expertise in the design and implementation of experiments using adequate techniques for identification, characterization, and quantification of lipids, particularly Cls. Prepare and optimally analyze samples to detect individual molecular species of lipids and oxidized lipids. 2. Provide opportunities for mass-spectrometric imaging of different types of individual molecular species and oxidized lipids in lung tissues. 3. Evaluate experimental results and propose subsequent experimental direction. 4. Provide training in the use of and access to any instrumentations and techniques used within the P01 project to assess lipidomics/oxidative lipidomics biomarkers. By assisting the Projects in the analytical work, the Core will facilitate studies of the mechanisms through which CL functions as a new molecular signal in acute lung injury hence contributes to the development of new therapeutic modalities.

目前，由于对ARDS发病机制认识不足，尚无有效的药物治疗方法。 P01 的首要重点是肺部对一种新的肺毒素和调节剂的反应机制，即阴离子磷脂、心磷脂 (CL)，其源自急性肺损伤期间受损宿主细胞的细菌或线粒体。因此，阐明 CL 不同分子种类、其代谢物及其与其他肺脂质及其过氧化产物的相互作用的新代谢和生化途径是 P01 的所有四个项目的基础。氧化脂质组学核心（核心 B）的设计使项目中的研究人员能够对 Cls 的所有主要分子种类、其他不同类别的脂质及其氧化产物进行详细分析 - 识别、表征和成像。这将通过使用基于不同版本的质谱 (MS) 与液相色谱 (LC) 或高性能薄层色谱 (HPTLC) 协议相结合的复杂的最先进技术来实现。氧化脂质组学核心 B 的具体目标是： 1. 使用适当的技术对脂质（特别是 Cls）进行鉴定、表征和定量，提供设计和实施实验的专业知识。制备并优化分析样品以检测脂质和氧化脂质的各个分子种类。 2. 为肺组织中不同类型的单个分子种类和氧化脂质的质谱成像提供机会。 3.评估实验结果并提出后续实验方向。 4. 提供使用和获取 P01 项目中使用的任何仪器和技术的培训，以评估脂质组学/氧化脂质组学生物标志物。通过协助项目的分析工作，核心将促进对 CL 作为急性肺损伤中新分子信号发挥作用的机制的研究，从而有助于新治疗方式的开发。