Megan L Stanifer,

Fun Fact: I love to travel, cook, and spend time with my two crazy kids. In the lab, I study how viruses try to evade sensing by the host and the mechanisms that the host uses to stop virus infection. I have used a diverse range of BSL-2 and BSL-3 viruses and have developed microscopy methods to visualize virus entry, and fusion, used single cell sequencing to unravel cell type specific responses to virus infection and implemented human mini-gut organoids to use models which more closely represent the natural infection. Our lab continues to use these techniques and focuses on virus infection at mucosal surfaces. Our primary aims are to establish complex in vitro organoid models from multiple mucosal surfaces using primary human cells to mimic the host cellular environment, to use live-cell microscopy to track virus infection and spreading within complex tissues, and to exploit fluorescent cellular reporters to follow how host cells upregulate their antiviral pathways to combat pathogen infection.

Intestinal epithelial cells are in constant contact with the ever-present commensal flora. This leaves them with a complex task of maintaining a fine balance between tolerating the microbiota and being ready to respond to invading pathogens. Intestinal cells are polarized with an apical side facing the lumen of the gut and a basolateral side facing the sterile lamina propria. Our work has uncovered that one method used by human intestinal epithelial cells (hIECs) to avoid over stimulation is that they polarize the pathogen-recognition receptor TLR‑3 to the basolateral side of hIECs to avoid over detection of the commensal bacteria. Our group continues to investigate the molecular mechanisms used by hIECs to maintain immune-homeostasis and how these mechanisms are mis-regulated in patients with inflammatory bowel disease by employing organoid cultures, live-cell imaging, and single cell sequencing. Additionally, we are now extending our observations in hIECs to additional mucosal tissues (e.g. the lung and genital tract) to determine if all tissues that act as a protect barrier use similar mechanisms to detect and fight invading pathogens while tolerating the presence of the commensal flora.