We are studying the mechanism by which sphingolipids regulate immunity and inflammation. Our focus has been on sphingosine-1-phosphate (S1P), a bioactive lipid enriched in the vascular and lymphatic systems, and the S1P receptors, found on immune cells and the endothelium. Essential roles for S1P and its receptors have been found for immune system development and homeostasis as well as for the regulation of immune responses and inflammation. We are studying the individual roles of the S1P receptors and the sphingolipid metabolic pathway in inflammation and immunity.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$599,767
Indirect Cost
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State
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Kono, Mari; Tucker, Ana E; Tran, Jennifer et al. (2014) Sphingosine-1-phosphate receptor 1 reporter mice reveal receptor activation sites in vivo. J Clin Invest 124:2076-86
Olivera, Ana; Kitamura, Yoshiaki; Wright, Laurel D et al. (2013) Sphingosine-1-phosphate can promote mast cell hyper-reactivity through regulation of contactin-4 expression. J Leukoc Biol :
Dillahunt, Sandra E; Sargent, Jennifer L; Suzuki, Ryo et al. (2013) Usage of sphingosine kinase isoforms in mast cells is species and/or cell type determined. J Immunol 190:2058-67
Olivera, Ana; Allende, Maria Laura; Proia, Richard L (2013) Shaping the landscape: metabolic regulation of S1P gradients. Biochim Biophys Acta 1831:193-202
Bonder, Claudine S; Sun, Wai Y; Matthews, Tyson et al. (2009) Sphingosine kinase regulates the rate of endothelial progenitor cell differentiation. Blood 113:2108-17
Liu, Guangwei; Burns, Samir; Huang, Gonghua et al. (2009) The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR. Nat Immunol 10:769-77
Ishii, Masaru; Egen, Jackson G; Klauschen, Frederick et al. (2009) Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis. Nature 458:524-8
Rivera, Juan; Proia, Richard L; Olivera, Ana (2008) The alliance of sphingosine-1-phosphate and its receptors in immunity. Nat Rev Immunol 8:753-63