Our research interests
We study the pathways by which microorganisms cross cellular barriers and the mechanisms by which these barriers restrict microbial infections. Our studies primarily focus on the epithelium that lines the gastrointestinal tract and on placental trophoblasts, the cells that comprise a key cellular barrier of the human placenta. Our work is highly multidisciplinary and encompasses aspects of cell biology, immunology, and microbiology. Our long-term goals are to identify pathogen- and host-specific therapeutic targets to prevent or treat microbial infections and ultimately to alleviate the morbidity and mortality caused by these infections.
Primary human intestinal organoid infected with coxsackievirus B. Actin staining in red and viral RNA is green (DAPI-stained nuclei in blue).
Enterovirus infections in the gastrointestinal tract
We are interested in defining the mechanisms by which enteroviruses enter and replicate in the GI tract and how this tissue responds to these infections. For these studies, we utilize human and mouse stem cell-derived enteroids and in vivo mouse models and focus on clinically relevant enteroviruses including coxsackievirus B (CVB), echoviruses, enterovirus 71 (EV71), and enterovirus D-68 (EV-D68).
Human trophoblast organoid. SDC-1 staining in green and cytokeratin-19 is in red (DAPI-stained nuclei in blue).
Antimicrobial signaling at the maternal-fetal interface
We are interested in defining the mechanisms by which the placenta restricts microbial access to the intrauterine compartment and how teratogenic pathogens including Toxoplasma gondii, CMV, Listeria monocytogenes, Group B strep, and Zika virus bypass these defenses. For these studies, we utilize human tissue, primary cells, organoids, and three-dimensional culture models.
Human stem cell-derived cerebral organoid immunostained for a marker of the forebrain (in green) and neurons (in red). DAPI-stained nuclei in blue.
Enterovirus infections at secondary tissue sites
We are interested in identifying receptors for enteroviruses and defining the role of these receptors in pathogenesis. Recently, we identified the neonatal Fc receptor (FcRn) as a primary receptor for echoviruses. Current studies in the lab are focused on using human stem cell-derived and in vivo mouse models to define the role of FcRn in echovirus pathogenesis in the liver and brain, two sites commonly associated with echovirus-induced disease.
On a chip perfusion-based model of the human fetal membrane. On the left are primary human amniotic epithelial cells and on the right are stem cell-derived organoids from chorion tissue from matched fetal membrane.
Models of human barrier cells
We are interested in establishing new models that allow for communication between diverse cell types comprising barrier tissues, such as the placenta and GI tract. These systems include co-culture assembloid models, membrane-based co-culture models, and perfusion-based models.
