Intestinal epithelial cells must balance nutrient absorption with barrier function. While bacterial proximity is typically assumed to be undesirable, epithelial cells tolerate colonization by commensal microbes, which can benefit the animal. Using genetics and gnotobiotics to manipulate both host and microbiota, we can study how epithelial cells respond to proximal bacteria in different biological contexts.
Bacterial adaptation to the epithelial surface can enhance microbiome stability, facilitate colonization resistance against pathogens, and confer different impacts on the host. We use unbiased methods including genetic screens and specific enrichment-based transcriptomics to uncover bacterial genetic factors involved in mucosal colonization.
We now know which types of bacteria make up the gut microbiome of humans and other mammals, and how some individual species can benefit their hosts. But we lack understanding of how microbiomes assemble, persist, and change over time. We have developed a variety of models and assays to quantify microbiome-relevant spatial and temporal colonization parameters.
IgA is the most abundantly-produced antibody in humans, and most of it is secreted in the intestine. We are studying how interactions between IgA, microbiota, and epithelial cells influence animal health and disease.
Epithelial cells, particularly in the intestine, exhibit incredible regenerative capacity. A cost to this is that when their proliferative functions go awry, these cells can become tumorigenic. We are studying how bacterial-epithelial interactions change during the transition from healthy epithelium to cancer.