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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Alexaki, Aikaterini; Clarke, Benjamin A; Gavrilova, Oksana et al. (2017) De Novo Sphingolipid Biosynthesis Is Required for Adipocyte Survival and Metabolic Homeostasis. J Biol Chem 292:3929-3939
Nugent, Adrienne; Proia, Richard L (2017) The role of G protein-coupled receptors in lymphoid malignancies. Cell Signal 39:95-107
Xiong, Yuquan; Lee, Hyuek Jong; Mariko, Boubacar et al. (2016) Sphingosine kinases are not required for inflammatory responses in macrophages. J Biol Chem 291:11465
Taguchi, Yoshimitsu; Allende, Maria L; Mizukami, Hiroki et al. (2016) Sphingosine-1-phosphate Phosphatase 2 Regulates Pancreatic Islet ?-Cell Endoplasmic Reticulum Stress and Proliferation. J Biol Chem 291:12029-38
Proia, Richard L; Hla, Timothy (2015) Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J Clin Invest 125:1379-87
Galvani, Sylvain; Sanson, Marie; Blaho, Victoria A et al. (2015) HDL-bound sphingosine 1-phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation. Sci Signal 8:ra79
Blaho, Victoria A; Galvani, Sylvain; Engelbrecht, Eric et al. (2015) HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation. Nature 523:342-6
Kono, Mari; Proia, Richard L (2015) Imaging S1P1 activation in vivo. Exp Cell Res 333:178-82
Weth, Daniela; Benetti, Camilla; Rauch, Caroline et al. (2015) Activated platelets release sphingosine 1-phosphate and induce hypersensitivity to noxious heat stimuli in vivo. Front Neurosci 9:140
Zhang, Wenliang; Mottillo, Emilio P; Zhao, Jiawei et al. (2014) Adipocyte lipolysis-stimulated interleukin-6 production requires sphingosine kinase 1 activity. J Biol Chem 289:32178-85

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