Erik J. Peterson, M.D. Assistant Professor Department of Medicine University of Minnesota, 1990, M.D. peter899@umn.edu 612-625-5634 - office

Research Interests:

Leukocyte activation and development

Biochemical signals generated through immune cell surface receptors play a key role in determining leukocyte development and behavior. Recently, members of a class of signaling proteins known as adaptors have been shown to play key roles in lymphocyte activation and development. Adaptors promote assembly of multi-protein complexes within cells. I have examined the role of one such hematopoietic-specific adaptor, Adhesion and Degranulation regulating Adaptor Protein (ADAP), in T cell signaling through study of ADAP-deficient mice. ADAP "knockout" T cells display impaired proliferation capacity when stimulated through the T cell receptor. ADAP-null cells also show impaired activation of integrins and faulty cellular adhesion. In addition, our recent work indicates that ADAP is required for optimal thymocyte development. Current studies focus upon the precise role played by ADAP in T cell receptor-dependent adhesion, natural killer cell function, and thymocyte selection.

Transformation of recently-discovered new knowledge about autoimmunity (rheumatoid arthritis, systemic lupus erythematosus, and Type I diabetes) susceptibility genes into candidate preventative and therapeutic strategies requires careful dissection of the biochemical and physiological mechanisms of action for these genes. A second major focus of my laboratory is on the use of genetically-altered animals and cell lines to permit more precise definition of the role of PTPn22, an human “lupus risk gene”, in the regulation of immunologic pathways that may be disrupted in autoimmunity. Our central hypothesis is that reduced TCR signaling engendered by LypW (the protein product of the PTPn22 gene) expression alters thymocyte selection thresholds, leading to abnormal survival of “self”-reactive T cells that could damage tissue. The Specific Aims of our current research include: 1) utilize LypW-expressing cell lines to study the role of LypW in T cell receptor signaling, 2) utilize LypW transgenic mice to evaluate effects of LypW expression upon thymocyte development and T cell function, and 3) quantify the effects of LypW in driving clinically-relevant animal models of lupus. Our approach will allow assessment of LypW function in genetically controlled, physiologically relevant, whole-animal model systems. We expect that the results of the research will advance understanding of the cellular and biochemical mechanisms whereby an autoimmunity susceptibility gene increases risk for tissue-damaging responses.

Selected Recent Publications:

• Bilgic H, Ytterberg, SR Amin, S McNallan KT, Wilson JC, Koeuth T. Ellingson S, Newman B, Bauer JW, Peterson EJ, Baechler EC, Reed AM. 2009. IL-6 and IFN-Regulated Genes and Chemokines Mark Disease Activity in Dermatomyositis (in press Arthritis and Rheumatism)

• Burbach BJ, .Srivastava R, Medeiros RB, O’Gorman WE, Peterson EJ, Shimizu Y. 2008. Distinct Regulation of Integrin-Dependent T Cell Congugate Formation and NF-kB Activation by the Adapter Protein ADAP. J Immunol. 181(7):4840-51.

• Zou L, Mendez F, Martin-Orozco, N, Peterson EJ. 2008. Defective positive selection results in T cell lymphopenia and increased autoimmune diabetes in ADAP deficient BDC2.5-BI/6 mice. Eur J Immunol. 38(4):986-94.

• Dluzniewska J, Zou L, Harmon IR, Ellingson MT, Peterson EJ. 2007. Immature hematopoietic cells display selective requirements for adhesion and degranulation-promoting adaptor protein in development and homeostasis. Eur J Immunol,; 37(11):3208-19.

• Mueller KL, Thomas MS, Burbach BJ, Peterson EJ, Shimizu Y. 2007. Adhesion and degranulation-promoting adapter protein (ADAP) positively regulates T cell sensitivity to antigen and T cell survival. J Immunol. 15;179(6):3559-69.

• Medeiros RB, Burbach BJ, Mueller KL, Srivastava R, Moon JJ, Highfill S, Peterson EJ, Shimizu Y. 2007. Regulation of NF-kappaB activation in T cells via association of the adapter proteins ADAP and CARMA1. Science,; 316(5825):754-8.

• Baechler EC, Batiwalla FM, Reed AM, Peterson EJ, Gaffney PM, Moser KL, Gregerson PK, Behrens TW. 2006. Genes expression profiling in human autoimmunity. Immunol Rev., 210:120-37.

• Stoeckman, A, Baechler, E., Ortmann, W., Behrens T., Michet, C., Peterson EJ. 2006. A distinct inflammatory gene expression profile in patients with psoriatic arthritis, Genes Immun., 7(7): 583-91.

• Fostel LV, Dluzniewska J, Shimizu Y, Burbach BJ, Peterson EJ. 2006. ADAP is dispensable for NK cell development and function. Int Immunol. 18(8):1305-14.
  

• Wu JN, Gheith S, Bezman NA, Liu QH, Fostel LV, Swanson AM, Freedman BD, Koretzky GA, Peterson EJ. 2006. Adhesion- and degranulation-promoting adapter protein is required for efficient thymocyte development and selection. J Immunol. 176(11):6681-9.

Last updated: August 11, 2009