The purpose of the Lipidomics Core in the SC Lipidomics and Pathobiology COBRE is to provide intellectual and physical resources (particularly state-of-the-art mass spectrometry analysis of sphingolipids and synthetic molecular tools to study importance of lipids) to enhance our understanding of the role of bioactive lipids in different diseases with the goal to discover future drugs. Core services include: 1) Providing synthetic molecular tools to study lipid metabolism (e.g., functionalized and fluorescent ceramides, site-specific radioactive sphingolipids) and diversified synthetic lipids and analogs for cellular, in vitro, and in vivo studies (e.g., organelle-targeted sphingolipids and organelle-targeted inhibitors of sphingolipid metabolizing enzymes). 2) Providing qualitative and quantitative analysis of lipid components from different biological materials (cells, tissue, and biological fluids), employing high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology. The core currently provides quantitative analysis of more than 200 distinct lipid molecular species. 3) Providing conceptual and practical training in various aspects of lipidology. The core also assists COBRE investigators in experimental design, selection of lipids of interest, and interpretation of analytical results. The Lipidomics Core of the Center for Lipidomics and Pathobiology at the Medical University of South Carolina (MUSC) is a novel scientific resource that provides synthetic and analytical services to biomedical investigators at MUSC. Owing to the unique nature of the services, collaborative investigators at research institutions around the world, as well as some pharma/biotech concerns, also have come to rely on this outstanding core resource. The COBRE Phase III transition for this Core builds upon previous investments of the NCRR COBRE Phase I and II programs, NCRR Shared Instrumentation Grants, NCI Program Project Grant Phase I and II programs, and NCI Cancer Center Support Grant program. This unique and very successful COBRE Core has developed into an institutional, national, and international resource.

Public Health Relevance

This proposal is to support several unique core resources that significantly enhance research on novel bioactive lipids that are involved in many important diseases including cancer, neurodegeneration, diabetes and cardiovascular disease. Moreover the research has significant impact on drug discovery and innovative biomedical industry that will benefit the economy of SC.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Center Core Grants (P30)
Project #
5P30GM103339-03
Application #
8714008
Study Section
Special Emphasis Panel (ZRR1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Medical University of South Carolina
Department
Type
DUNS #
City
Charleston
State
SC
Country
United States
Zip Code
29403
Spassieva, Stefka D; Ji, Xiaojie; Liu, Ye et al. (2016) Ectopic expression of ceramide synthase 2 in neurons suppresses neurodegeneration induced by ceramide synthase 1 deficiency. Proc Natl Acad Sci U S A 113:5928-33
Dany, Mohammed; Gencer, Salih; Nganga, Rose et al. (2016) Targeting FLT3-ITD signaling mediates ceramide-dependent mitophagy and attenuates drug resistance in AML. Blood 128:1944-1958
Yu, H; Sun, C; Argraves, K M (2016) Periodontal inflammation and alveolar bone loss induced by Aggregatibacter actinomycetemcomitans is attenuated in sphingosine kinase 1-deficient mice. J Periodontal Res 51:38-49
Podbielska, Maria; Szulc, Zdzisław M; Kurowska, Ewa et al. (2016) Cytokine-induced release of ceramide-enriched exosomes as a mediator of cell death signaling in an oligodendroglioma cell line. J Lipid Res 57:2028-2039
Novgorodov, Sergei A; Riley, Christopher L; Keffler, Jarryd A et al. (2016) SIRT3 Deacetylates Ceramide Synthases: IMPLICATIONS FOR MITOCHONDRIAL DYSFUNCTION AND BRAIN INJURY. J Biol Chem 291:1957-73
Yu, Hong; Herbert, Bethany A; Valerio, Michael et al. (2015) FTY720 inhibited proinflammatory cytokine release and osteoclastogenesis induced by Aggregatibacter actinomycetemcomitans. Lipids Health Dis 14:66
Venant, Heather; Rahmaniyan, Mehrdad; Jones, E Ellen et al. (2015) The Sphingosine Kinase 2 Inhibitor ABC294640 Reduces the Growth of Prostate Cancer Cells and Results in Accumulation of Dihydroceramides In Vitro and In Vivo. Mol Cancer Ther 14:2744-52
Geng, Tuoyu; Sutter, Alton; Harland, Michael D et al. (2015) SphK1 mediates hepatic inflammation in a mouse model of NASH induced by high saturated fat feeding and initiates proinflammatory signaling in hepatocytes. J Lipid Res 56:2359-71
Novgorodov, Sergei A; Riley, Christopher L; Yu, Jin et al. (2014) Essential roles of neutral ceramidase and sphingosine in mitochondrial dysfunction due to traumatic brain injury. J Biol Chem 289:13142-54
Snider, Ashley J (2013) Sphingosine kinase and sphingosine-1-phosphate: regulators in autoimmune and inflammatory disease. Int J Clin Rheumtol 8: