Kevin R. Lynch

About

Kevin R. Lynch is a Professor and Vice Chair of Pharmacology at the University of Virginia School of Medicine. He holds a BS in Microbiology from Pennsylvania State University, an MS in Microbiology from the University of Rhode Island, and a PhD in Molecular Biology from the University of Rhode Island. His research focuses on the biology of the lipid mediator sphingosine 1-phosphate (S1P), investigating how S1P concentration gradients influence immune cell positioning. Lynch's work explores the mechanisms of S1P signaling, including the development of small molecule inhibitors of the S1P transporter Spns2, which may offer therapeutic advantages over existing S1P receptor modulators used in autoimmune disease treatment. His research aims to reshape S1P gradients to improve drug efficacy and reduce adverse events associated with current therapies.

Research topics

• Biology
• Biochemistry
• Cell biology
• Chemistry
• Pharmacology
• Cancer research
• Pathology
• Genetics
• Medicine
• Internal medicine

Selected publications

• Sphingosine 1-phosphate signaling in perivascular cells enhances inflammation and fibrosis in the kidney

  Science Translational Medicine · 2022 · 57 citations

  Chronic kidney disease (CKD), characterized by sustained inflammation and progressive fibrosis, is highly prevalent and can eventually progress to end-stage kidney disease. However, current treatments to slow CKD progression are limited. Sphingosine 1-phosphate (S1P), a product of sphingolipid catabolism, is a pleiotropic mediator involved in many cellular functions, and drugs targeting S1P signaling have previously been studied particularly for autoimmune diseases. The primary mechanism of most…

  PublisherOA PDFDOI

• Mechanism of sphingosine 1-phosphate clearance from blood

  Biochemical Journal · 2020 · 35 citations

  Senior authorCorresponding

  The interplay of sphingosine 1-phosphate (S1P) synthetic and degradative enzymes as well as S1P exporters creates concentration gradients that are a fundamental to S1P biology. Extracellular S1P levels, such as in blood and lymph, are high relative to cellular S1P. The blood-tissue S1P gradient maintains endothelial integrity while local S1P gradients influence immune cell positioning. Indeed, the importance of S1P gradients was recognized initially when the mechanism of action of an S1P recepto…

  DOI

• Discovery of In Vivo Active Sphingosine-1-phosphate Transporter (Spns2) Inhibitors

  Journal of Medicinal Chemistry · 2022 · 32 citations

  has the potential for development and use as a probe to investigate Spns2 biology and to determine the potential of Spns2 as a drug target.

  PublisherOA PDFDOI

• Discovery of a Small Side Cavity in Sphingosine Kinase 2 that Enhances Inhibitor Potency and Selectivity

  Journal of Medicinal Chemistry · 2020 · 24 citations

  = 89 nM, 73-fold SphK2-selective) with validated in vivo activity.

  DOI

• Lipophilic tail modifications of 2-(hydroxymethyl)pyrrolidine scaffold reveal dual sphingosine kinase 1 and 2 inhibitors

  Bioorganic & Medicinal Chemistry · 2020-12-13 · 17 citations

  articleOpen access
  PublisherOA PDFDOI

Recent grants

• Controlling the flux of sphingosine-1-phosphate in vivo

  NIH · $3.5M · 2019–2024

• MD-PHAR Controlling sphingosine 1-phosphate synthesis and trafficking

  NIH · $2.1M · 2016–2021

• NIH Grant R01CA088994

  NIH · $782k · 2005

Frequent coauthors

• Timothy L. Macdonald

  California State University, Northridge

  74 shared

• Brian F. O’Dowd

  University of Toronto

  54 shared

• Jerold Chun

  Sanford Burnham Prebys Medical Discovery Institute

  52 shared

• Sarah Spiegel

  Virginia Commonwealth University

  52 shared

• Yugesh Kharel

  University of Virginia

  49 shared

• Susan R. George

  49 shared

• Webster L. Santos

  Virginia Tech

  45 shared

• Timothy Hla

  44 shared

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