Lynch, Kevin R.
Professor and Vice Chair, Pharmacology
- BS, Microbiology, Pennsylvania State University, University Park, PA
- MS, Microbiology, University of Rhode Island, Kingston, RI
- PhD, Molecular Biology, University of Rhode Island, Kingston, RI
- Postdoc, Molecular Biology, Columbia University
Biochemistry, Biotechnology, Cardiovascular Biology, Immunology, Molecular Pharmacology, Translational Science
Chemical biology of sphingosine 1-phosphate
Our research investigates the biology of the lipid mediator, sphingosine 1-phosphate (S1P). S1P concentration gradients are known to influence immune cell positioning. Indeed, S1P type 1 receptor agonist drugs are immunosuppressive by virtue of down regulating cell surface S1P1 receptors and thereby interdicting lymphocyte egress from lymph nodes to efferent lymph. While a set of S1P1 receptor modulator drugs are used clinically for treating autoimmune diseases, the class is beset by adverse events such as first dose bradycardia.
An alternative to masking the existence of S1P gradients from lymphocytes is to reshape the S1P gradients by inhibiting the S1P transporter, Spns2. Ideally, drugs blocking the release of cellular S1P will capture the efficacy of S1P receptor modulators with lessened adverse events. To test this idea, we are discovering and characterizing small molecule Spns2 inhibitors. Our inhibitors are proving useful as chemical probes to increase understanding of S1P signaling and may provide a path to developing a S1P transport blocking drug.