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Publications

Arthritis and Immunology Research Program

Dr. Harley In The News

Governor declares April Sjögren’s syndrome awareness month in Oklahoma

Harley named to the Association of American Physicians

OMRF research finds new cystic fibrosis gene

John B. Harley, M.D., Ph.D. Member and Program Chair, Arthritis and Immunology Research   Program George Lynn Cross Research Professor, University of Oklahoma Health Sciences   Center Professor of Medicine, Department of Medicine, University of Oklahoma Health    Sciences Center Adjunct Professor, Departments of Microbiology and Pathology, University of   Oklahoma Health Sciences Center Staff Physician, U.S. Department of Veterans Affairs Medical Center, Oklahoma   City

Research Interests
Systemic lupus erythematosus is an autoimmune disease primarily afflicting younger women. When left untreated, it can cause kidney failure, destruction of the blood cells, memory and thinking problems, strokes, heart attacks, arthritis and other serious health problems. For almost three decades we have studied the immune response and genetics of this disease.

Recognizing the strong genetic tendency of lupus, we have collected biological samples and data from more than 1,000 families having a member with the disease. In addition, we have collected this information from approximately 500 families having two or more afflicted members. We have identified 13 new genes associated with lupus. These genes introduce us to how the body responds in a way that generates lupus. The genes reinforce the importance of immunoglobulin receptors, the complement system and interferon. By explaining how these genes work to cause lupus will provide many opportunities to develop new diagnostics and therapeutics. We will be working to establish these genetic associations and to describe molecular mechanisms of disease that involve these genes.

We are also working to identify environmental factors in lupus. Our data suggest that for anti-Sm initiated lupus, autoimmunity arises through a molecular mimicry mechanism from the heterologous humoral immune response directed against Epstein-Barr virus nuclear antigen-a (EBNA-1). Recently, an analogous mechanism has been described for anti-Ro. Together, patients with anti-Sm and anti-Ro comprise over one-third of human lupus cases.

We have firmly established an association of Epstein-Barr virus infection with lupus, using multiple methods to test different groups that vary primarily in age. Results compiled from these experiments suggest that lupus begins after Epstein-Barr infection and progresses successively through EBNA-1 heterologous immunity, molecular mimicry with self-antigens, and benign autoimmunity, culminating in pathologic autoimmunity and disease. All of our environmental data are consistent with this model, with some of these results providing powerful statistical evidence that strongly supports its validity. Our future work will concentrate on testing and refining the details of immune function in this model and integrating these ideas with the newly discovered genes that help cause lupus.

Joined OMRF Scientific Staff in 1982.

Mailing Address
Arthritis and Immunology Research Program, MS 24
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, Oklahoma 73104

Contact Information
Phone: (405) 271-6673
Fax: (405) 271-3980
E-mail: John-Harley@omrf.org