Sphingosine 1-Phosphate in Neurovascular Biology and Disease (SphingoNet)

European Coordinator:
  • Christer BETSHOLTZ, Uppsala University, Uppsala, Sweden
North American Coordinator:
  • Timothy HLA, Boston Children's Hospital, USA

Eric CAMERER, Université Paris Descartes, Paris, France
Annika KELLER, Zürich University, Switzerland
Costantino IADECOLA, Weill Medical College of Cornell University, New York, New York, USA
Josef PFEILSCHIFTER, Goethe University, Frankfurt, Germany
Waltraud PFEILSCHIFTER, Goethe University, Frankfurt, Germany
Richard PROIA, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA
Lawrence STEINMAN, Stanford University, Stanford, California, USA

 Understanding the control and regulation of the BBB is of significant clinical importance because the BBB remains one of the major obstacles in the delivery of drugs to the central nervous system.  The transatlantic network led by Christer Betsholtz and Timothy Hla brings together experts in blood vessels, immunology and nervous system function to focus on the central role of sphingosine 1-phosphate (S1P) in the development and regulation of the neurovascular unit and blood brain barrier (BBB) in health and disease. This is a novel approach to the investigation of the neurovascular unit prompted by the discovery of a drug that influences sphingosine signaling and has been found to be effective in multiple sclerosis.  The network project will further characterize the role of S1P in ischemia.  When dysregulated, S1P signaling causes neuroinflammation and neurovascular disease. As very little is known about S1P and its receptor systems that are expressed on multiple cell types and tissues in vessels and brain, the proposed experiments will concentrate on genetic targeting of receptors and related pathways. Building on a strong body of literature implicating S1P in vascular regulation and blood brain barrier permeability, network members propose specifically to identify the cell types responsive to SIP-mediated BBB regulation in large part by the use a variety of genetically engineered mice.   If successful this group could help to launch a entirely new platform for the treatment of neurovascular disease.