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Immunobiology and Cancer Research Program

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Linda Thompson, Ph.D. Member, Immunobiology and Cancer Research Program Putnam City Schools Distinguished Chair in Cancer Research Adjunct Professor, Departments of Microbiology and Immunology, University of   Oklahoma Health Sciences Center

Research Interests
Research in my laboratory concerns the role of ecto-5′-nucleotidase (CD73), a purine metabolizing enzyme, in generating adenosine for adenosine receptor signaling. Ecto-5′-nucleotidase is a glycosyl phosphatidylinositol (GPI)-anchored enzyme that catalyzes the dephosphorylation of extracellular AMP to adenosine. Adenosine receptors are seven transmembrane spanning G-protein coupled receptors that regulate many important aspects of physiology. We are using CD73-deficient mice, created in our lab, to learn more about the ability of CD73 to generate adenosine for adenosine receptor signaling. CD73-/- mice appear healthy and reproduce normally but show exaggerated responses to a variety of inflammatory stimuli. For example, they exhibit a vascular leak syndrome characterized by neutrophil accumulation in tissues, especially the lung, when exposed to hypoxia. They also show elevated cytokine responses in experimental models of colitis, sepsis, and pulmonary inflammation and fibrosis. CD73-deficient mice exhibit increased lymphocyte migration to the draining lymph nodes after exposure to an inflammatory stimulus. Surprisingly, CD73-deficient mice are resistant to the development of experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. The development of EAE depends upon the ability of pathogentic T cells to enter the central nervous system. These findings suggest that CD73-generated adenosine plays an important role in regulating leukocyte migration across endothelial and epithelial barriers in a variety of physiological or pathological settings. Future studies will investigate the mechanism by which adenosine either inhibits or promotes leukocyte trafficking under specific experimental circumstances. We are also investigating the importance of the GPI anchor of CD73 in its ability to provide adenosine for adenosine receptor signaling using newly-created transgenic mice expressing CD73 with a conventional transmembrane anchor.

We are also participants in a multi-investigator project to understand why some lupus patients fail to make adequate responses to immunization with the influenza vaccine. In collaboration with Drs. Judith James, Sherry Crowe, Michelle Joachims, Gillian Air (at OUHSC), Patrick Wilson (at University of Chicago), Mark Coggeshall, and Joel Guthridge, we are studying various aspects of the immune response to influenza vaccination in lupus patients and healthy matched control subjects. The role of my lab is to investigate the cellular immune response. Our study is part of a larger NIH Biodefense program to improve vaccine responses in immunocompromised individuals including the very young, the elderly, patients receiving chemotherapy, organ transplant recipients, and patients with autoimmune diseases.

Joined OMRF Scientific Staff in 1989.

Mailing Address
Immunobiology and Cancer Research Program, MS 29
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, Oklahoma 73104

Contact Information
Phone: (405) 271-7235
Fax: (405) 271-7128
E-mail: Linda-Thompson@omrf.org