Modulation of Viral Infection and Pathogenesis by Defensins

Defensins are a family of antimicrobial peptides that are an evolutionarily conserved effector component of the innate immune response.  Although their antibacterial properties are well established in vitro and in vivo, their antiviral activity is less well understood.  The Smith Lab is interested in uncovering the molecular mechanisms by which defensins alter non-enveloped viral infection and understanding the role of these molecules in viral pathogenesis in vivo.

Innate Immune Sensing of Enteric Pathogens

Epithelial cells are on the front lines of host-microbe interactions in the gut.  They express a number of innate immune sensing pathways for microbes.  One such pathway is the inflammasome.  In collaboration with Leigh Knodler at Washington State University and Bruce Vallance at the University of British Columbia, we have been investigating how inflammasome sensing of Salmonella enterica contributes to pathogenesis.  An important technology for these studies is the use of human enteroid “mini-gut” cultures that allow us to study untransformed, patient-derived human intestinal epithelial cells.

IBD and Paneth Cell Biology

We are interested in understanding how genetic changes associated with Crohn’s Disease, a type of inflammatory bowel disease (IBD), alter the function of intestinal epithelial cells, with a focus on Paneth cells.  We use enteroid technology to culture Paneth cells in the lab and test their function.  Our ultimate goal is to be able to take tissue from a patient through a biopsy, perform tests on them in the lab, and then determine from the test results whether the patient has or is likely to develop IBD, which of their genetic changes might be contributing to the severity of the disease, and what therapies might resolve flare-ups and prevent future inflammation.