The sphingolipid metabolic pathway yields highly active lipid signaling molecules that regulate many physiologic processes during development and for homeostasis in the adult. Furthermore, the pathway is highly regulated and appears to function abnormally in certain disordered states such as in cancer and in metabolic diseases. We are utilizing genetically altered mice that are modified in their sphingolipid metabolism and signaling to uncover new functions of sphingolipids in normal biology and in disease.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2012
Total Cost
$668,672
Indirect Cost
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Taguchi, Yoshimitsu; Allende, Maria L; Mizukami, Hiroki et al. (2016) Sphingosine-1-phosphate Phosphatase 2 Regulates Pancreatic Islet β-Cell Endoplasmic Reticulum Stress and Proliferation. J Biol Chem 291:12029-38
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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
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Gupta, Sita D; Gable, Kenneth; Alexaki, Aikaterini et al. (2015) Expression of the ORMDLS, modulators of serine palmitoyltransferase, is regulated by sphingolipids in mammalian cells. J Biol Chem 290:90-8
Tabeling, Christoph; Yu, Hanpo; Wang, Liming et al. (2015) CFTR and sphingolipids mediate hypoxic pulmonary vasoconstriction. Proc Natl Acad Sci U S A 112:E1614-23
Kono, Mari; Proia, Richard L (2015) Imaging S1P1 activation in vivo. Exp Cell Res 333:178-82
Proia, Richard L; Hla, Timothy (2015) Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J Clin Invest 125:1379-87
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
Giannouli, Christina C; Chandris, Panagiotis; Proia, Richard L (2014) Visualizing S1P-directed cellular egress by intravital imaging. Biochim Biophys Acta 1841:738-44

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