We are exploring the hypothesis that biased agonists of the S1PRs will have unique signaling properties and therefore specific pharmacological properties. In addition, functional antagonists that target S1PRs to degradative pathways will likely lead to unique pharmacological properties and able to target specific disease-associated S1P functions. Using high throughput and high content screens, we are developing novel inhibitors of S1PRs with increased specificity and efficacy in vascular and inflammatory/ immune diseases.
In addition, S1P chaperones are engineered as novel biotherapeutics in the treatment of vascular, immune, inflammatory and lung diseases using pre-clinical mouse models. The figure shows the crystal structure of ApoM bound to S1P - the residues that coordinate the phosphate head group are highlighted.