SC COBRE: LIPIDOMICS CORE

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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.