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Dr. Esmon:

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Cardiovascular Biology Research Program

  

Naomi L. Esmon, Ph.D.
Associate Member, Cardiovascular Biology Research Program
Adjunct Professor, Department of Pathology, University of Oklahoma Health
  Sciences Center

Research Interests
My laboratory is interested in understanding how the body controls blood coagulation. We are most interested in how the activated protein C (APC) pathway, a vital anticoagulant pathway, functions and how it can be blocked in diseases, leading to the formation of life-threatening blood clots (thromboses). In recent years, we have found that the membrane requirements of the APC anticoagulant complex differ markedly from those of the procoagulant complexes. Specifically, phosphatidylethanolamine is essential for maximum activity. Oxidation of the membrane phospholipids further enhances APC activity with little effect on the procoagulant reactions.

A significant number of patients, many with autoimmune disease, have antibodies that are associated with thrombotic complications. Other individuals with apparently similar antibodies do not thrombose. We have recent data showing that autoantibodies that specifically block the phospholipid oxidation dependent enhancement of APC activity are found much more frequently in patients with autoimmune disease who have had a thrombotic event. Interestingly, the oxidation dependence inhibition is even true for antibodies that react with the plasma protein b2-glycoprotein I. This is the first evidence that an antibody directed to a general membrane-binding protein can have a specific effect on one of the coagulation reactions. Such antibodies may explain why individuals clot only intermittently when an inflammatory stimulus, leading to membrane oxidation, is present.

It is the goal of our lab to better understand the membrane requirements of the APC pathway and determine the relationship between the differential membrane structure requirements of the procoagulant and anticoagulant reactions and the specificity of pathogenic antibodies. The role of oxidation is of particular interest, as it is a common feature in inflammatory diseases, including cardiovascular disease, lupus and many other chronic illnesses.

Prospective studies to determine the utility of these assays, combined with testing for antibodies to various other members of the APC pathway in predicting thrombotic events will be undertaken. We hope that research into the molecular mechanisms involved in the membrane specificities of the coagulation reactions and pathological antibodies will lead to better predictive and monitoring tests for those individuals in need of prophylactic treatment. Such assays in turn should aid in the development of more specific and safer therapeutic drugs for cardiovascular disease.

Joined OMRF Scientific Staff in 1976.

Mailing Address
Cardiovascular Biology Research Program, MS 45
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, Oklahoma 73104

Contact Information
Phone: (405) 271-6673
E-mail: Naomi-Esmon@omrf.org