Pathology

E-mail: janis.weis@path.utah.edu
Address: 15 N Medical Drive #2100
Phone: 581-8386

The Mechanism of Inflammatory Arthritis Development

My laboratory investigates the mechanism of inflammatory arthritis development, using the murine model of Lyme disease.  Our goals are to identify the events associated with arthritis development in this model of acute, infection-associated disease, with the understanding that these events may set the stage for chronic autoimmune arthritis in susceptible individuals.  Mice of the C3H strain develop severe arthritis when infected with Borrelia burgdorferi, whereas C57BL/6 mice develop mild arthritis.  We are using several different genetic approaches to understand the differences in arthritis severities and the pathways associated with the development of severe and mild disease.  Expression profiling of joint tissue has revealed striking differences in infected mice destined to develop severe verses mild disease.  Severe arthritis is associated with induction of and interferon profile, similar to identified in human and murine lupus.  Resistance to arthritis is associated with an epidermal development profile, with features of wound repair.  Identification of these two, disparate pathways provides a model for understanding the differential response to infection.  We are currently using quantitative trait loci (QTL) analysis to identify candidate genes regulating arthritis severity, and using a variety of knock out mice to understand the regulation of these expression profiles.  Our hypothesis is that it is the initial response of the resident cells of the joint to the invading bacteria that determines the severity of arthritis.  Student projects include assessment of inflammatory pathways activated in cell types in response to B. burgdorferi.  This includes the identification and assessment of the contribution of candidate genes to arthritis development, and a study of the effect of variety of clinically relevant inhibitors on the development of arthritis.

1/2008