The emerging Center in Lipidomics and Pathobiology at the Medical University of South Carolina (MUSC) builds on substantial accomplishments during the first two phases of the COBRE. These include mentoring of 19 targeted junior faculty investigators, 14 of whom have achieved independent extramural funding, 193 publications in peer-review journals by the target faculty, participation by more than 25 MUSC research faculty in COBRE activities, and development and enhancement of highly successful, innovative scientific core facilities, including a unique core in Lipidomics, and emerging focused cores in animal pathobiology (focused on lipid-based animal models) and a protein core focused on lipid enzymes and targets. The COBRE has also been very successful in recruiting minorities (2) and women (10) as target faculty. The organizing hypothesis states that the universe of bioactive lipids and related metabolites constitutes a complex network of diverse pathways regulating key physiologic functions. In turn, dysfunctions in these pathways contribute to the pathobiology of specific diseases. Counterbalancing the biological significance of lipids are unique considerations that arise from the relative difficulties of studying lipids and lipid-interacting proteins. These necessitate the development of competent shared facilities and collaborative efforts to bring various disciplines and expertise to bear on specific problems. Therefore, the strategic focus of the next phase is to achieve the development of a stand-alone Center of Lipidomics and Pathobiology at MUSC that will build on these remarkable scientific and institutional achievements and that will continue to catapult lipid research at MUSC. The overall objective is to capitalize on the exceptional strengths at MUSC in lipid biology with specific goal to: 1) define and develop specific thematic programmatic activities focusing on important pathobiology based on Center activities (e.g. cancer, neurodegeneration, metabolic disorders and infection/inflammation);2) enhance translational research;3) enhance mentoring to meet the increasing challenges of the current funding environment;4) enhance the function of the cores and position them to better serve thematic and translational goals;5) complete the development of the novel Lipidomics Portal;and 6) develop and achieve sustainability of the cores. We anticipate that these activities will result in a highly developed interdisciplinary research center with a critical mass of collaborative, independently and programmatically funded investigators in an evolving area of research of major significance to cancer biology, aging, inflammation, diabetes, neurodegeneration and infectious diseases.
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.
|Kim, Soohyun P; Frey, Julie L; Li, Zhu et al. (2017) Lack of Lrp5 Signaling in Osteoblasts Sensitizes Male Mice to Diet-Induced Disturbances in Glucose Metabolism. Endocrinology 158:3805-3816|
|Scheffel, Matthew J; Helke, Kristi; Lu, Ping et al. (2017) Adoptive Transfer of Ceramide Synthase 6 Deficient Splenocytes Reduces the Development of Colitis. Sci Rep 7:15552|
|Ghatak, Shibnath; Markwald, Roger R; Hascall, Vincent C et al. (2017) Transforming growth factor ?1 (TGF?1) regulates CD44V6 expression and activity through extracellular signal-regulated kinase (ERK)-induced EGR1 in pulmonary fibrogenic fibroblasts. J Biol Chem 292:10465-10489|
|Ghatak, Shibnath; Hascall, Vincent C; Markwald, Roger R et al. (2017) Transforming growth factor ?1 (TGF?1)-induced CD44V6-NOX4 signaling in pathogenesis of idiopathic pulmonary fibrosis. J Biol Chem 292:10490-10519|
|Bai, Aiping; Mao, Cungui; Jenkins, Russell W et al. (2017) Anticancer actions of lysosomally targeted inhibitor, LCL521, of acid ceramidase. PLoS One 12:e0177805|
|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|
|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|
|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|
|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|
|Podbielska, Maria; Szulc, Zdzis?aw 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|
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