The Laboratory of Erik Peterson at the University of Minnesota

Dr. Erik J. Peterson, Principal Investigator

Peterson Lab Overview

The laboratory strives toward several broad objectives. First, we aim to understand molecular mechanisms of action for “risk” genes recently associated with human autoimmune disease. Second, we work to identify molecular requirements for tissue-injuring inflammation that attends autoimmune syndromes. The laboratory uses primary human samples, transformed cell lines, and animal models to approach questions concerning the biochemical, cellular, and immune response-modulating functions of autoimmunity factors and susceptibility alleles. Major current projects include:

1) Genetic Determinants of Autoimmunity: PTPN22 is among the strongest genetic factors predisposing to several major human autoimmune diseases, including Type 1 Diabetes (T1D), Rheumatoid Arthritis (RA), and Systemic Lupus Erythematosus (SLE). PTPN22 encodes lymphoid tyrosine phosphatase (Lyp). A Lyp protein variant bearing a R620W substitution (“LypW”) causes enhanced risk of autoimmune disease.

The Peterson group strives to contribute to a comprehensive model of PTPN22 and LypW mechanisms of action. Working with collaborators at UMN and at the La Jolla Institute of Allergy and Immunology, our group demonstrated that PTPN22 plays a key positive role in regulating pattern recognition receptor (PRR) signaling leading to production of type 1 Interferons (IFN) by myeloid cells (Wang et al, Immunity 2013; PMID 23871208). We established that Lyp protein binds and promotes activation of TNF Receptor Associated Factor 3 (TRAF3) during myeloid cell PRR signaling. Lyp also promotes PRR-induced, type 1 IFN-driven anti-viral host defense and suppression of inflammation in colitis and arthritis in animal models. Importantly, the LypW variant exhibits reduced-function behavior in PRR signaling and in type 1 IFN-governed suppression of inflammation.
Our observation that PTPN22 modulates myeloid cell signaling suggests new potential mechanisms whereby an autoimmunity-associated gene works in concert with environmental stimuli such as viral infections or inflammatory reactions to result in tissue damage. Our working model holds that PTPN22 potentiates myeloid cell-directed, type 1 IFN-dependent, anti-microbial host defense and counter-inflammatory processes. The model also holds that the reduced-function LypW variant enhances potential for autoimmunity by increasing host susceptibility to tissue damage by suboptimally-suppressed infections and/or inflammatory reactions.

Questions under active investigation in 2014 include:
A) Is myeloid cell-intrinsic PTPN22 function sufficient for major host defense and anti-inflammatory actions in vivo?

B) What is the molecular basis for PTPN22 promotion of TRAF3 signaling?

C) Does LypW exhibit differential function in type 1 IFN-driven processes such as response to immunization, anti-fungal host defense, and inflammation suppression?
D) How do Lyp functions in host-defense and inflammation suppression translate into autoimmune disease risk?

By addressing such questions experimentally, we seek to identify novel therapeutic targets, high-quality biomarkers, and ultimately, cures for human rheumatic and autoimmune disease.

2) Pathogenesis of idiopathic inflammatory myopathy: Dermatomyositis exemplifies a group of uncommon but life- and organ-threatening autoimmune syndromes collectively known as idiopathic inflammatory myopathy (IIM). Patients with DM suffer debilitating muscle weakness, respiratory impairment, and disfiguring skin rashes. Organ damage in DM is associated with intense inflammatory and immune reactions, both systemic and local; however, the key cellular and molecular instigators of immune dysfunction are unknown. Our collaborative genomic and proteomic studies in peripheral blood reveal striking association between DM disease activity and levels of IL-6, as well as with levels of type I Interferon (IFN)-driven genes and proteins.

We hypothesize that molecules related to the IL-6 and IFN proinflammatory pathways will serve as sensitive biomarkers of disease activity and severity in DM, and act as key driving forces in the immunopathology of DM. In collaboration with the Ann Reed group at the Mayo Clinic, we are addressing these hypotheses through several approaches. We are determining the precise anatomic and cellular location of IL-6 and type 1 IFN in diseased human DM muscle. We are assessing the requirements for and sufficiency of IL-6 and type 1 IFN-related molecules in an animal model of myositis. In addition, we are determining the predictive and diagnostic value of measuring peripheral blood components of the type 1 IFN axis in a longitudinal study of Mayo Clinic DM patients. We anticipate that our results will shed new light on the immunopathogenesis of DM, will establish the value of novel biomarkers for DM disease activity assessment, and will quantitate therapeutic potential of manipulating IL-6 and/or type 1 IFN in inflammatory myositis.

Dr. Peterson Contact Information

Laboratory: 612-625-0661


Recent developments

  • New Grant funding for 2016 The Peterson Lab is honored to be the recipient of a grant from the Lupus Foundation of Minnesota. Funding will support experimental work under the title "The role of SLE risk gene PTPN22 in Candida Immunity." The work will be conducted between 1-2015 and 1-2016.
    Posted Dec 15, 2015, 9:12 AM by Andrea Stewart
  • Grant application approved The Peterson group is honored to receive new funding from the Alliance for Lupus Research, a prestigious grant-making organization. Funding will support experimental work under the title "Targeting interferogenic signals regulated by SLE risk gene PTPN22." The work will be conducted between 2-2014 and 1-2017.
    Posted Dec 30, 2013, 7:45 AM by Erik Peterson MD
  • Grant Funding by the Peterson Lab The Peterson Laboratory is honored to have received 2013 funding from the Lupus Foundation of Minnesota to further their research in SLE.
    Posted Jan 8, 2013, 8:39 AM by Sarah Potter
  • New Grant for the Lab! The Peterson Lab is happy to announce new funding from the American Diabetes Association for the project "The role of PTPn22, diabetes risk gene, in Type 1 interferon regulation" Work will begin immediately on this project which will run from 1/1/12-12/31/2014.
    Posted Mar 7, 2012, 1:24 PM by Sarah Potter
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