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David Stephen Pisetsky, PhD, MD

Professor of Medicine
Campus Mail: VA Med Ctr, 508 Fulton St, Durham, NC 27705
Phone: (919) 286-6835
Email: david.pisetsky@duke.edu

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.

Education and Training

  • M.D., Albert Einstein College of Medicine of Yeshiva University, 1973
  • Ph.D., Albert Einstein College of Medicine of Yeshiva University, 1972

Selected Publications

Rutledge, HR, Jiang, W, Yang, J, Warg, LA, Schwartz, DA, Pisetsky, DS, and Yang, IV. "Gene expression profiles of RAW264.7 macrophages stimulated with preparations of LPS differing in isolation and purity." Innate Immun 18, no. 1 (February 2012): 80-88.

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Distler, JHW, Akhmetshina, A, Dees, C, Jüngel, A, Stürzl, M, Gay, S, Pisetsky, DS, Schett, G, and Distler, O. "Induction of apoptosis in circulating angiogenic cells by microparticles." Arthritis Rheum 63, no. 7 (July 2011): 2067-2077.

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Ullal, AJ, Reich, CF, Clowse, M, Criscione-Schreiber, LG, Tochacek, M, Monestier, M, and Pisetsky, DS. "Microparticles as antigenic targets of antibodies to DNA and nucleosomes in systemic lupus erythematosus." J Autoimmun 36, no. 3-4 (May 2011): 173-180.

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Pisetsky, DS, Gauley, J, and Ullal, AJ. "Microparticles as a source of extracellular DNA." Immunol Res 49, no. 1-3 (April 2011): 227-234.

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Pisetsky, DS. "Platelet microparticles: making blood a bad humor." J Rheumatol 38, no. 4 (April 2011): 590-592.

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Pisetsky, DS. "The role of HMGB1 in efferocytosis: when the dead go unburied. Focus on "HMGB1 inhibits macrophage activity in efferocytosis through binding to the alphavbeta3-integrin"." Am J Physiol Cell Physiol 299, no. 6 (December 2010): C1253-C1255.

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Pisetsky, DS, and Ullal, AJ. "The blood nucleome in the pathogenesis of SLE." Autoimmun Rev 10, no. 1 (November 2010): 35-37. (Review)

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Pisetsky, DS. "Charlie's List." Ann Intern Med 153, no. 5 (September 7, 2010): 344-.

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Gauley, J, and Pisetsky, DS. "The release of microparticles by RAW 264.7 macrophage cells stimulated with TLR ligands." J Leukoc Biol 87, no. 6 (June 2010): 1115-1123.

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Ullal, AJ, and Pisetsky, DS. "The release of microparticles by Jurkat leukemia T cells treated with staurosporine and related kinase inhibitors to induce apoptosis." Apoptosis 15, no. 5 (May 2010): 586-596.

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Pisetsky, DS. "HMGB1: a dangerous player in lupus pathogenesis." J Rheumatol 37, no. 4 (April 2010): 689-691.

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Ullal, AJ, Pisetsky, DS, and Reich, CF. "Use of SYTO 13, a fluorescent dye binding nucleic acids, for the detection of microparticles in in vitro systems." Cytometry A 77, no. 3 (March 2010): 294-301.

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Grundtman, C, Bruton, J, Yamada, T, Ostberg, T, Pisetsky, DS, Harris, HE, Andersson, U, Lundberg, IE, and Westerblad, H. "Effects of HMGB1 on in vitro responses of isolated muscle fibers and functional aspects in skeletal muscles of idiopathic inflammatory myopathies." FASEB J 24, no. 2 (February 2010): 570-578.

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Beyer, C, and Pisetsky, DS. "The role of microparticles in the pathogenesis of rheumatic diseases." Nat Rev Rheumatol 6, no. 1 (January 2010): 21-29. (Review)

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Pisetsky, DS, and Vrabie, IA. "Antibodies to DNA: infection or genetics?." Lupus 18, no. 13 (November 2009): 1176-1180. (Review)

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