David Stephen Pisetsky, MD, PhD

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Professor of Medicine
Professor of Immunology
Department / Division:
Medicine / Medicine-Rheumatology and Immunology
Address:
DUMC 3544
Durham, NC 27710
Appointment Telephone:
Not accepting new patients
Office Telephone:
919-286-6835
Fax:
919-286-6891
Training:
  • MD, PhD, Albert Einstein College of Medicine of Yeshiva University (New York), 1973
Residency:
  • Medicine, Yale-New Haven Hospital (Connecticut), 1973-1975
  • Immunology, National Institutes of Health (Maryland), 1975-1978
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.
Representative Publications:
  • Rutledge, HR; Jiang, W; Yang, J; Warg, LA; Schwartz, DA; Pisetsky, DS; Yang, IV. Gene expression profiles of RAW264.7 macrophages stimulated with preparations of LPS differing in isolation and purity. Innate immunity. 2012;18:80-88.  Abstract
  • Distler, JH; Akhmetshina, A; Dees, C; Jüngel, A; Stürzl, M; Gay, S; Pisetsky, DS; Schett, G; Distler, O. Induction of apoptosis in circulating angiogenic cells by microparticles. Arthritis and Rheumatism. 2011;63:2067-2077.  Abstract
  • Pisetsky, DS. Platelet microparticles: making blood a bad humor. Journal of Rheumatology. 2011;38:590-592.  Abstract
  • Pisetsky, DS; Gauley, J; Ullal, AJ. Microparticles as a source of extracellular DNA. Immunologic Research: a selective reference to current research and practice. 2011;49:227-234.  Abstract
  • Ullal, AJ; Reich, CF; Clowse, M; Criscione-Schreiber, LG; Tochacek, M; Monestier, M; Pisetsky, DS. Microparticles as antigenic targets of antibodies to DNA and nucleosomes in systemic lupus erythematosus. Journal of Autoimmunity. 2011;36:173-180.  Abstract
  • Beyer, C; Pisetsky, DS. The role of microparticles in the pathogenesis of rheumatic diseases. Nature Reviews. Rheumatology. 2010;6:21-29.  Abstract
  • Gauley, J; Pisetsky, DS. The release of microparticles by RAW 264.7 macrophage cells stimulated with TLR ligands. Journal of Leukocyte Biology. 2010;87:1115-1123.  Abstract
  • Grundtman, C; Bruton, J; Yamada, T; Ostberg, T; Pisetsky, DS; Harris, HE; Andersson, U; Lundberg, IE; Westerblad, H. Effects of HMGB1 on in vitro responses of isolated muscle fibers and functional aspects in skeletal muscles of idiopathic inflammatory myopathies. The FASEB Journal. 2010;24:570-578.  Abstract
  • Pisetsky, DS. Charlie's List. Annals of Internal Medicine. 2010;153:344.  Abstract
  • Pisetsky, DS. HMGB1: a dangerous player in lupus pathogenesis. Journal of Rheumatology. 2010;37:689-691.  Abstract
  • 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". American Journal of Physiology: Cell Physiology. 2010;299:C1253-C1255.  Abstract
  • Pisetsky, DS; Lipsky, PE. Microparticles as autoadjuvants in the pathogenesis of SLE. Nature Reviews. Rheumatology. 2010;6:368-372.  Abstract
  • Pisetsky, DS; Ullal, AJ. The blood nucleome in the pathogenesis of SLE. Autoimmunity Reviews. 2010;10:35-37.  Abstract
  • Ullal, AJ; Pisetsky, DS. The release of microparticles by Jurkat leukemia T cells treated with staurosporine and related kinase inhibitors to induce apoptosis. Apoptosis: an international journal on programmed cell death. 2010;15:586-596.  Abstract
  • Ullal, AJ; Pisetsky, DS; Reich, CF. Use of SYTO 13, a fluorescent dye binding nucleic acids, for the detection of microparticles in in vitro systems. Cytometry Part A. 2010;77:294-301.  Abstract
  • Crowley, SD; Vasievich, MP; Ruiz, P; Gould, SK; Parsons, KK; Pazmino, AK; Facemire, C; Chen, BJ; Kim, HS; Tran, TT; Pisetsky, DS; Barisoni, L; Prieto-Carrasquero, MC; Jeansson, M; Foster, MH; Coffman, TM. Glomerular type 1 angiotensin receptors augment kidney injury and inflammation in murine autoimmune nephritis. Journal of Clinical Investigation. 2009;119:943-953.  Abstract
  • Gauley, J; Pisetsky, DS. The translocation of HMGB1 during cell activation and cell death. Autoimmunity. 2009;42:299-301.  Abstract
  • Pisetsky, DS. Microparticles as biomarkers in autoimmunity: from dust bin to center stage. Arthritis Research and Therapy. 2009;11:135.  Abstract
  • Pisetsky, DS; Rönnblom, L. Systemic lupus erythematosus: a matter of life and death. Arthritis and Rheumatism. 2009;60:1567-1570.  Abstract
  • Pisetsky, DS; Vrabie, IA. Antibodies to DNA: infection or genetics?. Lupus. 2009;18:1176-1180.  Abstract
  • Reich, CF; Pisetsky, DS. The content of DNA and RNA in microparticles released by Jurkat and HL-60 cells undergoing in vitro apoptosis. Experimental Cell Research. 2009;315:760-768.  Abstract
  • Su, KY; Pisetsky, DS. The role of extracellular DNA in autoimmunity in SLE. Scandinavian Journal of Immunology. 2009;70:175-183.  Abstract