Department / Division:
Medicine
/
Rheumatology and Immunology
Address:
DUMC 3544
Durham, NC 27710
Appointment Telephone:
Not accepting new patients
Office Telephone:
919-286-6835
Fax Telephone:
919-286-6891
Clinical Interests:
Rheumatoid arthritis, systemic lupus erythematosus, general rheumatology
Research Interests:
Studies in my laboratory concern the immunological properties of DNA as related to two main topics: 1) the induction of anti-DNA responses in systemic lupus erythematosus; and 2) the stimulation of innate immunity by bacterial DNA. These topics are closely linked since we have established novel disease models in which lupus-like illness can be induced in normal mice by bacterial DNA under conditions in which mammalian DNA is inactive. This model has been useful in elucidating mechanisms of DNA antigen drive in autoimmunity.
To pursue these studies, our laboratory conducts investigations in the following areas: 1) specificity of anti-DNA for epitopes on mammalian and bacterial DNA; 2) molecular analysis of murine mononclonal anti-DNA antibodies; 3) histopathological analyses of DNA-immunized mice; 4) in vitro analysis of proliferation, antibody production and cytokine expression in human and murine immune cells; and 5) analysis of DNA binding to cell surface molecules on B cells, T cells and macrophages. Results of these studies have allowed identification of at least two structural motifs that are immunoactive. We are also exploring the impact of chemical modifications of the DNA backbone.
In addition to work on the immunology of DNA, I am also involved in clinical trials related to new immunomodulatory agents in the treatment of rheumatoid arthritis as well as serological markers of disease activity.
The areas of research for which I am known nationally are anti-DNA antibodies, systemic lupus erythematosus and immunological properties of DNA. I have written textbook chapters and reviews on all these subjects.
Key Words: anti-DNA; autoimmunity; systemic lupus erythematosus; immunological properties of DNA; and antinuclear antibodies.
Representative Publications:
5. Wloch, M.K., A.L. Alexander, A.M.M. Pippen, D.S. Pisetsky and G.S. Gilkeson. Molecular properties of anti-DNA induced in preautoimmune NZB/W mice by immunization with bacterial DNA. J. Immunol. 158 (1997) 4500-4506
(1997)
4. Gilkeson, G.S., P. Ruiz, A.M.M. Pippen, A.L. Alexander, J.B. Lefkowith, and D.S. Pisetsky. Modulation of renal disease in autoimmune NZB/NZW mice by immunization with bacterial DNA. J. Exp. Med. 183 (1996) 1389-1397.
(1996)
3. Pisetsky, D.S. Immunological properties of DNA. J. Immunol. 156 (1996) 421-423.
(1996)
2. Halpern, M.D., R.J. Kurlander and D.S. Pisetsky. Bacterial DNA induces murine interferon gamma production by stimulation of interleukin-12 and tumor necrosis factor alpha. Cell Immunol. 167 (1996) 72-78.
(1996)
1. Gilkeson, G.S., A.M.M. Pippen, and D.S. Pisetsky. Induction of cross-reactive anti-dsDNA antibodies in preautoimmune NZB/NZW mice by immunization with bacterial DNA. J. Clin. Invest. 95 (1995) 1398-1402.
(1995)