Janet Frances Staab, PhD

Primary Academic Title

Assistant Professor of Medicine

Background

Research Interests

Candida albicans, Epithelial/microbial interactions, intestinal organoids/enteroids, molecular mycology

Research Summary

The first step in a successful infection is the attachment of a pathogenic microorganism to the host cell. Microorganisms have developed strategies to facilitate adhesion to mammalian cells, many of which exploit the host’s own physiology to gain attachment and often times, entry into host cells. In defense of possible invading microorganisms, the mammalian mucosa has innate immunity strategies to impede microbe adhesion and proliferation that can lead to infection. An important innate immune strategy of the intestinal mucosa is to maintain a functioning mucosal barrier, aided by the microbiome and underlying immune cells. When mucosal surface innate immunity is compromised, opportunistic and true pathogens can gain a foothold, grow and cause infection. There are still many areas of mucosal innate immunity that prevent microbial attachment that are not completely understood. How mucosal innate immune strategies vary with commensal vs. opportunistic vs. pathogenic microorganisms are of interest to our group.

Normally, the yeast Candida albicans, exists in the gastrointestinal tract as a harmless commensal organism. However, disturbance of mucosal innate immunity allows for the yeast to overgrow, attach and invade epithelial cells. C. albicans utilizes surface proteins called adhesins to attach to oral epithelial cells. Whether C. albicans adhesins are equally important for attachment and invasion of human intestinal epithelial cells is not completely understood. We are using human primary, adult stem cell-derived intestinal organoids or enteroids to investigate the strategies of C. albicans adhesion to understand mucosal aspects that permit attachment vs. epithelial mechanisms that prevent adhesion and preserve the commensal status of the yeast within the gut. The development and use of enteroids, a physiologically relevant model of the human intestinal mucosa, will allow us to investigate C. albicans interactions with not only epithelial cells but with epithelial cells in the context of immune cells. 

Fungal dysbiosis has been associated with inflammatory bowel diseases. Colonization and increased number of C. albicans yeasts are frequently found in Crohn’s disease patients. Enteroids derived from inflammatory bowel disease patients maintain their pathophysiology phenotype and will help us understand mucosal differences between healthy and CD enteroids in the context of C. albicans adhesion and invasion.

Together, our research interests will reveal mechanisms of C. albicans/intestinal epithelial cell interactions to develop strategies or targets to address C. albicans dysbiosis in the human gut.