SC COBRE: LIPIDOMICS CORE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 具体目标 具体目标不变。 研究和结果 该中心已全面投入运作，并向项目调查人员提供以下支助： 1.合成脂质、其类似物和脂质代谢抑制剂，目前重点关注鞘脂。 合成鞘脂和调节鞘脂代谢的化合物（例如神经酰胺酶和鞘氨醇激酶抑制剂）、特异性细胞器靶向神经酰胺类似物（线粒体和溶酶体）和侧特异性放射性鞘脂已交付用于细胞、体外和体内研究，可供COBRE研究者使用 2.生物材料中鞘脂成分的定性定量分析。 基于高效液相色谱-串联质谱（LC-MS/MS）技术的分析结果来自几位HCC研究者的不同细胞系、组织、血清和培养基。目前，我们提供鞘氨醇碱、鞘氨醇碱磷酸盐、神经酰胺、磷酸神经酰胺鞘磷脂、己糖神经酰胺、葡萄糖神经酰胺、半乳糖神经酰胺、乳糖神经酰胺和二酰基甘油（DAG）组分的同时定性和定量分析。此外，还可通过LC-MS/MS分析对生物材料中外源添加的药物进行定量。 3.协助COBRE研究人员设计和实施旨在研究生物活性脂质及其代谢、分析和功能的实验方法。 应要求提供了全力支持。 4.改进和开发脂质分析的新技术，开发新的合成分子工具，以研究生物活性脂质和新的潜在抗癌药物的作用。 采用超临界色谱-质谱联用技术（SFS-MS/MS）分离异构己糖神经酰胺：葡萄糖神经酰胺和半乳糖神经酰胺，并对其分子组成进行定量分析。 合成了酸性神经酰胺酶和鞘氨醇激酶的新的亲溶酶体抑制剂，可供COBRE研究人员使用。 意义 该设施建立的LC-MS/MS方法允许在基本代谢组学分析的同时分析生物活性鞘脂。这将有助于研究人员了解鞘脂的生物合成和周转如何调节细胞行为，以及一种鞘脂的扰动如何增强或干扰另一种鞘脂的作用。该设施开发的鞘脂代谢途径抑制剂可作为有效的抗癌剂。 该设施提供了独特的脂质分析和独特的合成工具，这些工具在所有项目中都得到了高度利用。 计划 我们将按照最初的计划继续提供服务。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Specific Aims The specific aims are unchanged. Studies and Results The core is in full operation and is providing the following support to project investigators: 1. Synthetic lipids, their analogs, and inhibitors of lipid metabolism with a current emphasis on sphingolipids. Synthetic sphingolipids and compounds that modulate sphingolipid metabolism (e.g. inhibitors of ceramidases and sphingosine kinases), specific organelle- targeting ceramide analogs (mitochondria and lysosomes) and side-specific radioactive sphingolipids have been delivered for use in cellular, in vitro and in vivo studies are available for COBRE investigators 2. Qualitative and quantitative analysis of sphingolipid composition from biological materials. Analytical results based on High Performance Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) technique were generated from different cell lines, tissues, serum and media, for several HCC investigators. Currently, we provide simultaneous qualitative and quantitative analysis of sphingoid bases, sphingoid base phosphates, ceramide, ceramide phosphate sphingomyelin, hexosylceramides, glucosyl ceramides, galactosylceramides lactosylceramides and diacyl-glycerol (DAG's) components. Additionally, a quantitation of exogenously added drugs to the biological materials is also available by the LC-MS/MS analysis. 3. Assistance for COBRE investigators in the design and conduct of experimental approaches aimed at the study of bioactive lipids, their metabolism, analysis and function. Full support was provided upon requests. 4. Improvement and development of the new techniques for lipid analysis and development of new synthetic molecular tools to study the role of bioactive lipids and new potential anticancer agents. Separation of isomeric hexosylceramides: glucosyl-ceramide and galactosyl-ceramide and quantitative analysis of their molecular components has been developed using a new analytical approach combining supercritical chromatography separation and mass spectrometry detection (SFS-MS/MS). New lysosomotropic inhibitors of acid ceramidase and sphingosine kinase were synthesized and are available for the COBRE investigators. Significance LC-MS/MS approach established by this facility allows a simultaneous analysis of bioactive sphingolipids at a basic metabolomic profiling. This will help researchers to understand how sphingolipid biosynthesis and turnover regulate cell behavior and how perturbations in sphingolipids of one type may enhance or interfere with the action of another. Inhibitors of sphingolipid metabolic pathways developed by this facility act as potent anticancer agents. This facility provides a unique analysis of lipids and unique synthetic tools that are being highly utilized in all projects. Plans We plan to continue our service as originally proposed.