Professor, Department of Pediatrics
Director, Center for Microbial Pathogenesis
Associate Director, R.K. Mellon Institute for Pediatric Research
Education & Training
Ph.D.: University of North Carolina at Chapel Hill
Post-doctoral Fellowship: Children's Hospital of Philadelphia/University of Pennsylvania
Research Interests
The Coyne laboratory studies the pathways by which viruses cross cellular barriers and the mechanisms by which these barriers restrict viral infections. Research primarily focuses on the polarized epithelium that lines the gastrointestinal tract and placental trophoblasts, which comprise the primary cellular barrier of the human placenta. The lab focuses on delineating the pathways targeted by RNA viruses, e.g., enteroviruses and flaviviruses, to promote their replication and spread. The work is highly multidisciplinary and encompasses aspects of cell biology, tissue engineering, immunology, and microbiology.
Specific Research Areas
The placental barrier
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 maternal circulation. The research program asks two central questions (1) what are the mechanisms by which the placenta restricts the vertical transmission of microorganisms and (2) how do microorganisms associated with congenital disease breach the placental barrier? The lab 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, several key questions remain, including: (1) are there differences in the mechanisms employed by the placenta to restrict microbial access at different stages of gestation, (2) what mechanisms are used by the placenta to defend against non-viral pathogens, and (3) what is the influence of the systemic maternal immune response on placental antimicrobial defenses?
The gastrointestinal barrier
The human gastrointestinal (GI) tract is a complex organ, with an epithelial surface that provides 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, coxsackievirus, echovirus, 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. We recently developed two human models of the GI epithelium to better define enterovirus-GI interactions. These include a cell line-based three-dimensional model and a human primary stem cell-derived enteroid model. Ongoing research in the laboratory is focused on defining the mechanisms by which enteroviruses bypass the GI barrier to initiate infection using these organotypic 3-D cell models, with a specific focus on the cell biological and immunological events associated with enterovirus infections of the GI tract.
Cellular pathways targeted by RNA viruses to promote their replication
RNA viruses usurp a variety of host cell pathways to facilitate their replication. Our studies focus on 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 autophagy and on the identification of mechanisms employed by RNA viruses to specifically modulate the host autophagic pathway.