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Cardiovascular Biology Research Program

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A Vicious Cycle: New OMRF research sheds light on epileptic seizures

Rodger P. McEver, M.D. Member and Program Chair, Cardiovascular Biology Research Program Alvin Chang Chair in Cardiovascular Biology Adjunct Professor, Department of Biochemistry and Molecular Biology, University   of Oklahoma Health Sciences Center Co-director, MD/PhD Training Program, University of Oklahoma Health Sciences   Center

In my lab, we study how circulating blood cells attach to blood vessel surfaces at sites of tissue injury or infection.  Substances released at these sites direct the endothelial cells that line blood vessels to display "adhesion molecules."  These molecules enable circulating white blood cells, or leukocytes, to roll along the vessel surface.  The rolling cells then slow to a stop and then crawl between the endothelial cells into the tissues, where they destroy invading microbes.  This process is known as inflammation.  Similarly, circulating platelets use adhesion molecules to roll along tissues that are exposed when blood vessels are disrupted.  The platelets then stop and form clumps to slow hemorrhage and promote blood clotting.  Inflammation and blood clotting are often linked.  Indeed, leukocytes sometimes roll on and then stick to blood platelets.  Excessive inflammation and blood clotting contribute towards many diseases, including heart attacks, stroke, dysfunction of transplanted organs, deep vein thrombosis, and sickle cell crisis.

Three adhesion molecules, called selectins, direct the initial rolling of leukocytes on endothelial cells and platelets.  Our lab discovered one of the selectins, which is displayed on both endothelial cells and platelets, and also discovered its interacting partner, or ligand, on leukocytes.  Examination of the molecular details of how selectins bind to their ligands has suggested means to inhibit these interactions in disease.  We also collaborate with bioengineers to study how cellular and molecular features adjust to complex fluid dynamics to facilitate blood cell adhesion under flow.  This work involves sophisticated video microscopy to visualize cell adhesion in flow chambers that mimic the conditions in the circulation.

Finally, my lab has generated a variety of genetically engineered mice in which key adhesion or signaling molecules have been deleted or modified.  These mice provide powerful tools for investigating molecular function in models of inflammation or blood clotting in living animals.