The research in my laboratory is aimed at understanding the role of extracellular matrix to inflammatory cell recruitment and activation involved in diseases of the intestine and lung.
Our laboratory focuses on cellular mechanisms pertinent to the inflammatory processes associated with inflammatory bowel disease (Crohn’s disease and ulcerative colitis) and concentrates on altered pathways of extracellular matrix synthesis and catabolism as both cause and effect of inflammation. The etiology of inflammatory bowel disease (IBD), similar to many other inflammatory diseases, is unknown, no doubt because multiple factors are at play to initiate, drive and sustain immune responses.
Hyaluronan (HA), an extracellular matrix component, is increased in inflamed human colon during flares of IBD and in animal models of colitis, where it precedes leukocyte infiltration. In cell culture, certain cellular stimuli, such as viruses and the inflammatory cytokine tumor necrosis factor-a, can induce the deposition of HA by smooth muscle cells and endothelial cells, respectively. HA produced under these conditions is in a form that adheres to leukocytes, suggesting its role in inflammation.
Investigators have shown that as a polymer, HA favors homeostasis, whereas in its degraded state it takes on pro-inflammatory, pro-angiogenic properties. We have found that, via a specific enzyme, platelets have the ability to clip HA into inflammation-promoting fragments that signal leukocytes.
We envision a scenario during tissue damage in which HA is produced by the structural cells and leakage of platelets into the area causes HA fragment formation, leukocyte activation and promotion/perpetuation of inflammation.
