Key Publications

 
 
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.

 
Human mid-gestation placental chorionic villi.

Human mid-gestation placental chorionic villi.

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.   

 
Dengue virus infection in human blood brain barrier microvascular endothelial cells.

Dengue virus infection in human blood brain barrier microvascular endothelial cells.

Cell biology of RNA virus replication.

RNA viruses usurp a variety of host cell pathways to facilitate their replication. One of the key missions of the Coyne Lab is identifying the pathways targeted by RNA viruses (including enteroviruses and flaviviruses) to promote their replication and spread.

An obligate step in the life cycle of positive sense RNA viruses is the formation of membrane-enriched organelles, termed replication organelles, that provide the structural support for viral replication. Multiple mechanisms have been proposed for the generation of these membranes, including manipulation of the host autophagic pathway, a process that removes damaged organelles via the formation of double membrane bound vesicles. Current studies in the laboratory are focused on the identification and characterization of novel regulators of host cell authophagy and on the identification of mechanisms employed by RNA viruses to specifically modulate the host autophagic pathway.