Inflammation is an integral part of our natural defense against infection, protecting us from a whole host of foreign organisms. However, when unchecked this innate immune process can work against us and instead lead to chronic disease. Our laboratory focuses on inflammatory bowel disease (IBD), a severe and chronic lifelong condition leading to relentless destruction of the gastrointestinal tract. IBD consists of two related but clinically distinct disorders (Crohn’s disease and ulcerative colitis) with a clear need for improved, innovative treatments. Immune dysregulation is a hallmark of IBD and our studies focus on multiple roles of extracellular matrix (ECM) components such as the glycan hyaluronan (HA) as an information-rich system that instructs cells and contributes to the progression and chronic nature of IBD. In response to tissue injury, HA acquires a unique `cable-like’ structure and is highly adhesive for naïve leukocytes and platelets, occupying an interface between inflammation and coagulation. Thrombotic events are characteristic extraintestinal features of IBD but the consequences of abnormal platelet responses and how platelets modify the immune response in IBD requires further study.
We seek to understand: 1) how does HA regulate hypercoagulability during inflammation; 2) how do platelets recognize and regulate inflammatory HA matrices; 3) what is the mechanism driving platelet hyperreactivity in IBD; 4) how do platelets modulate leukocyte recruitment and activation, and 5) what are the signaling pathways governed by HA in platelets and endothelial cells.
Our ultimate goal is to better understand how glycans modulate the immune system and leverage this knowledge for developing new therapeutics and diagnostic tools for IBD and other thromboinflammatory disorders.
Aaron Petrey, PhD
Assistant Professor Microbiology & Immunology
Department of Pathology
Division of Microbiology and Immunology
University of Utah