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Dr. Thompson:

Dr. Thompson 101
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Dr. Thompson's CV in brief

Publications

Immunobiology and Cancer Research Program

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
esearch in my laboratory concerns lymphocyte development and the function of two purine metabolizing enzymes, ecto-5’-nucleotidase (CD73) and adenosine deaminase (ADA). Ecto-5’-nucleotidase is a glycosyl phosphatidylinositol (GPI)-anchored enzyme that catalyzes the dephosphorylation of extracellular AMP to adenosine and, therefore, can regulate adenosine receptor signaling. We are using CD73-deficient mice, created in our lab, to learn more about the function of this enzyme. 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. These findings suggest that CD73-generated adenosine plays an important role in regulating leukocyte migration across endothelial barriers in a variety of physiological or pathological circumstances. Future studies will investigate 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.

ADA mutations cause severe combined immunodeficiency in humans. We used murine fetal thymic organ cultures to show that ADA-deficient fetal thymuses exhibit a block in thymocyte differentiation due to the accumulation of dATP. Our results are consistent with the hypothesis that dATP, derived from the ADA substrate deoxyadenosine, induces cytochrome c release from mitochondria followed by the initiation of the apoptotic cascade. Future experiments will focus on the consequences of ADA deficiency on the development of human thymocytes.

The mechanism by which T cells commit to either the ab or gd lineage is a fundamental question in T-cell biology. We are using a combination of molecular and cell culture approaches to define the role of the T-cell receptor (TCR) in this process. Our results using human thymocytes suggest that gd development is the default pathway and that ab lineage cells are derived from those thymocytes that are unable to rearrange their g and/or d loci productively. Compared to murine T cell development, human thymocytes lose gd potential and commit to the ab lineage gradually throughout several phenotypic stages. Knowledge of the pathways of thymocyte differentiation is important for understanding the pathogenesis of immunodeficiency diseases, autoimmunity and T lymphoid malignancies.

Finally, we are involved in a multi-investigator project to understand why some lupus patients fail to make adequate responses to immunization with the influenza vaccine.

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