Key Publications

 

Three-dimensional image reconstruction of a human trophoblast organoid grown in Matrigel.

Three-dimensional image reconstruction of a human trophoblast organoid grown in suspension.

Trophoblast organoid derived from rhesus macaque placental tissue.

Decidua organoid derived from rhesus macaque placental tissue.

Organoid models of the maternal-fetal interface. 

Across the evolutionary tree, the placenta has diversified extensively in both structure and cellular composition, all while preserving its essential role in supporting and protecting developing offspring. Trophoblasts, fetal-derived cells fundamental to nutrient transfer and immune protection, are a universal component across all placentas. While placentas from various mammalian lineages share core functions, species-specific differences in gene expression and cellular architecture remain largely unexplored, in part due to limited in vitro models. To bridge this gap, we have developed organoid models from the placentas of different species, including both fetal-derived trophoblasts and maternal-derived decidua cells, providing new opportunities to compare placental biology across evolutionary contexts.

 

Antimicrobial signaling at the maternal-fetal interface. 

The placenta is unlike any other human organ. Given its essential role in protecting the fetus, the placenta must function as a barrier and conduit between the maternal and fetal environments and serve as an active immunological tissue that responds to microbes present in the maternal circulation. Our research program asks two central questions:

  1. What are the mechanisms by which the placenta restricts the vertical transmission of microorganisms?

  2. How do microorganisms associated with congenital disease breach the placental barrier?

Our studies have established a new and important paradigm – that in addition to its role as a physical barrier, the placenta is a dynamic and highly reactive chemical barrier that uses multiple classes of molecules, including type III interferons and microRNAs, to protect the fetus and maternal host from viral infections. However, our investigations continue to probe important questions to learn if there are differences in the mechanisms employed by the placenta to restrict microbial access at different stages of gestation and to understand what mechanisms are used by the placenta to defend against non-viral pathogens. Further, we hope to define the influence of the systemic maternal immune response on placental antimicrobial defenses.   

Human stem cell-derived enteroid.

Human stem cell-derived enteroid.

 

Enterovirus infections of barrier cells.

The human gastrointestinal (GI) tract is a complex organ, with an epithelial surface that must provide a protective and immunological barrier in a complex and diverse microbial environment. Enteroviruses are leading causes of human infections worldwide, particularly in infants and children, and infect primarily via the fecal-oral route. These viruses, which include poliovirus, coxsackieviruses, echoviruses, enterovirus D68 (EV-D68), and enterovirus 71 (EV71), are small, single-stranded RNA viruses belonging to the Picornaviridae family.

The events that surround enterovirus infections of the human GI epithelium remain poorly understood. Our laboratory is interested in developing models to better define the mechanisms associated with enterovirus infections in the GI tract. We are also interested in identifying the host factors and pathways that facilitate enterovirus entry, replication, and spread from the GI epithelium.