Schwab Lab Home
The signaling lipid sphingosine-1-phosphate (S1P) plays critical roles in mammalian biology. The concentration of S1P is high in blood, and plasma S1P stabilizes junctions between vascular endothelial cells. The concentration of S1P is low in lymphoid tissues compared to blood and lymph, and S1P compartmentalization is required to maintain proper lymphocyte circulation. Although S1P in lymphoid organs is low in homeostasis, S1P may increase upon inflammation, and increases in tissue S1P have been reported to promote angiogenesis and to enhance pro-inflammatory responses of innate and adaptive immune cells. Drugs targeting S1P signaling and S1P metabolism are in clinical trials as immune suppressants. By blocking exit from lymphoid organs, these drugs prevent activated T cells from reaching transplanted organs or organs that are subject to autoimmune attack. These drugs may also have direct anti-inflammatory effects. Despite S1P’s vital functions, little is understood about how its distribution is controlled. Our lab is developing tools to map S1P in homeostasis and disease, exploring what regulates S1P concentration in tissues, and testing how S1P shapes inflammation. We are also investigating broader questions about both S1P-dependent and S1P-independent lymphocyte trafficking.