Our Approach

We aim to study biology that is directly relevant to human health. For that reason, our research questions are based on findings identified in human patient samples and data. We then develop experimental model systems to investigate the underlying mechanisms and functional consequences of our findings in humans. The model systems we commonly use are the laboratory mouse and intestinal spheroid culture.

Approach

Research Topics

We recently identified epithelial defects associated with microvilli in non-inflamed Crohn’s disease intestinal tissue, including a down-regulated cluster of genes associated with the microvilli brush border and a histological decrease in microvilli length (VanDussen et al. Gastroenterol, 2018). These defects correlated with clinical parameters related to disease severity and response to treatment. We hypothesize that these microvilli defects contribute to chronic disease progression in a subset of Crohn’s patients. We are testing this hypothesis in expanded patient cohorts and in experimental model systems.

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We do not yet know the biological driver of the microvilli-associated epithelial defects observed in Crohn’s disease intestinal tissue. We are taking a variety of approaches to determine if (and which) host or luminal exposures of the epithelial cell might be driving the altered expression of the microvilli signature genes and microvilli length. One approach is to determine if these microvilli-associated traits persist in patient-derived spheroid cell lines, in the absence of the host and luminal exposures. This knowledge will critically inform the design of future studies and potential therapeutic approaches to restore these epithelial cell functions.

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