Kevin R. Lynch
Professor of Pharmacology and Biochemistry & Molecular Genetics
Ph.D., University of Rhode Island
Molecular Pharmacology of Lysophospholipid Mediators

 

Our research program seeks to increase understanding of the biology and pathobiology of the lysophospholipid mediator, sphingosine 1-phosphate (S1P). We use primarily chemical biology approaches and secondarily mutant mouse models in our research. We are particularly focused on developing drug-like molecules to rigorously test the hypothesis that interdiction of S1P signaling at the level of synthesis is a viable therapeutic strategy. Other areas of interest include the mechanism of uptake of sphingoid bases by cells, the routes of S1P metabolism and the function of putative mitochondrial lipid kinase.


Selected References

Bajwa A, Huang L, Ye H, Dondeti K, Song S, Rosin DL, Lynch KR, Lobo PI, Li L,Okusa MD. (2012) "Dendritic cell sphingosine 1-phosphate receptor-3 regulates Th1-Th2 polarity in kidney ischemia-reperfusion injury." J Immunol. Sep 189:2584-96. doi: 10.4049/jimmunol.1200999. Epub 2012Aug 1. [PubMed]

Kharel Y, Raje M, Gao M, Gellett AM, Tomsig JL, Lynch KR, Santos WL. (2012) "Sphingosine kinase type 2 inhibition elevates circulating sphingosine 1-phosphate." Biochem J. Oct 447:149-57. doi: 10.1042/BJ20120609. [PubMed]

Gellett AM, Kharel Y, Sunkara M, Morris AJ, Lynch KR. (2012) "Biosynthesis of alkyl lysophosphatidic acid by diacylglycerol kinases." Biochem Biophys Res Commun. Jun 422:758-63. doi:10.1016/j.bbrc.2012.05.077. Epub 2012 May 22. [PubMed]

Knott K, Kharel Y, Raje MR, Lynch KR, Santos WL. (2012) "Effect of alkyl chain length on sphingosine kinase 2 selectivity." Bioorg Med Chem Lett. Nov 22(22):6817-20. doi:10.1016/j.bmcl.2012.01.050. Epub 2012 Jan 26. [PubMed]

Raje MR, Knott K, Kharel Y, Bissel P, Lynch KR, Santos WL. (2012) "Design, synthesis and biological activity of sphingosine kinase 2 selective inhibitors." Bioorg Med Chem. Jan 20:183-94. doi: 10.1016/j.bmc.2011.11.011. Epub2011 Nov 15. [PubMed]

Kharel Y, Mathews TP, Gellett AM, Tomsig JL, Kennedy PC, Moyer ML, Macdonald TL, Lynch KR. (2011) "Sphingosine kinase type 1 inhibition reveals rapid turnover of circulating sphingosine 1-phosphate." Biochem J. Dec 440:345-53. doi: 10.1042/BJ20110817. [PubMed]

Kennedy PC, Zhu R, Huang T, Tomsig JL, Mathews TP, David M, Peyruchaud O,Macdonald TL, Lynch KR. (2011) "Characterization of a sphingosine 1-phosphate receptor antagonist prodrug." J Pharmacol Exp Ther. 338:879-89. doi: 10.1124/jpet.111.181552. Epub 2011 Jun 1. [PubMed]

Kennedy AJ, Mathews TP, Kharel Y, Field SD, Moyer ML, East JE, Houck JD, LynchKR, Macdonald TL. (2011) "Development of amidine-based sphingosine kinase 1 nanomolar inhibitors and reduction of sphingosine 1-phosphate in human leukemia cells." J Med Chem. May 54(10):3524-48. doi: 10.1021/jm2001053. Epub 2011 May 2. [PubMed]

Kharel Y, Mathews TP, Kennedy AJ, Houck JD, Macdonald TL, Lynch KR. (2011) "A rapid assay for assessment of sphingosine kinase inhibitors and substrates." Anal Biochem. Apr 411:230-5. doi: 10.1016/j.ab.2011.01.003. Epub 2011 Jan 7. [PubMed]

Bajwa A, Jo SK, Ye H, Huang L, Dondeti KR, Rosin DL, Haase VH, Macdonald TL,Lynch KR, Okusa MD. (2010) "Activation of sphingosine-1-phosphate 1 receptor in the proximal tubule protects against ischemia-reperfusion injury." J Am Soc Nephrol. 21:955-65. doi: 10.1681/ASN.2009060662. Epub 2010Mar 25. [PubMed]