The Coyne Lab for Virus Research

Discovering the Biological Gatekeepers to Virus Spread

Researchers within the laboratory of Carolyn Coyne, PhD, study 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. In addition to studying cellular barriers, the Coyne Lab focuses on delineating the pathways targeted by RNA viruses (such as 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. 

Areas of Focus

The Placental Barrier

Placental BarrierThe 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:

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

The Gastrointestinal Barrier

Gastrointestinal BarrierThe 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, 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. Using these organotypic 3D cell models, the lab team is focused on defining the mechanisms by which enteroviruses bypass the GI barrier to initiate infection, specifically focusing 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

Zika VirusRNA 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.

Lab Team & Contact Information

Carolyn Coyne, PhD

Principal Investigator
coynec2@pitt.edu
Read More>>

Stephanie Ander
Graduate Student
sta23@pitt.edu

Nitin Arora, MD
Clinical Fellow
aroran@pitt.edu

Jacqueline Corry, PhD
Postdoctoral Fellow
corry.18@pitt.edu

Azia Evans
Graduate Student
aziaevans@pitt.edu

Kaman Fan
Scholar
kaf154@pitt.edu

Megan Freeman, MD
Clinical Fellow
megan.freeman@chp.edu

Charles Good
Research Technician
charlesgood@pitt.edu

Nicholas Lennemann, PhD
Postdoctoral Fellow
nil33@pitt.edu

Jen Melvin
Administrative Assistant – Senior
melvinjl@upmc.edu

Stefanie Morosky
Lab Manager
stm39@pitt.edu

Contact Us

The Coyne Lab
UPMC Children’s Hospital of Pittsburgh
John G. Rangos Sr. Research Center, Suite 9116
4401 Penn Avenue
Pittsburgh, PA 15224
412-692-7519

News & Activities

View current news below featuring the research, staff and advancements of the Coyne Lab for Virus Research at UPMC Children’s Hospital of Pittsburgh’s Richard King Mellon Institute for Pediatric Research. Please check back often for continued updates.

The Zika Virus

Science in the Crosshairs
NPR Science Friday (10/14/2016)

As Zika Cases Fade, Pitt Researchers Look for Clues on How the Virus is Transmitted, especially in pregnant women
Pittsburgh Post-Gazette (8/7/2016)

We Know How Women Get Zika. But How Does The Virus Reach Their Babies?
NPR’s Weekend Edition (8/7/2016)

1 Organ Holds the Key to Zika's Devastating Birth Defects
Scientific American (5/16/2016)

A Race to Unravel the Secrets of the Zika Virus
The New York Times (5/9/2016)

Zika Virus Transmission Still Mysterious
NPR Science Friday (4/15/2016)

The Zika Virus: Unlocking its Secrets
CBS KDKA News (2/12/2016)

Virus Profilers Race To Figure Out What Makes Zika Tick
NPR’s All Things Considered (2/9/2016)

Placenta Work

Studies Shine Light on Mysterious Placenta, How it Goes Awry
National Post (8/11/2016)

The Greatest Barrier Reef: Teaching Placental Cells to Live in a Dish
Pitt Med (Summer 2016)

New Placenta Model Uses Space-age Technology
The Pitt News (3/24/2016)

3-D Cell Placenta Model Mimics Development, Microbial Resistance
National Institutes of Health (3/15/2016)

New Placenta Model Could Reveal How Birth Defect-causing Infectious Agents Cross From Mother to Baby
Science Daily (3/7/2016)

New Human Placenta Model For Studying Infection Resistance
Reliawire (3/7/2016)

Not Going Viral: How the Placenta Protects the Fetus
Pitt Med (Fall 2013)

Enterovirus Work

Scientists are Trading in Lab Mice for Hundreds of Mini-Brains on a Chip
Wired (2/9/17)

Inside Passage: Researchers Shed Light on How Viruses Enter the Intestine
Science and Technology Research News (2/1/2017)

'Mini-guts' Offer Clues to Pediatric GI Illness
Science Daily (1/31/2017)

‘Mini-guts’ Show How Nasty Virus Invades
Futurity (1/31/2017)

Cozzarelli Prize

Pitt/MWRI Researchers Awarded Prestigious Cozzarelli Prize for Top Biomedical Sciences PNAS Paper of 2013
McGowan Institute for Regenerative Medicine (3/7/2014)

Two sides to a Coyne
This Week in Virology Podcast (12/13/2015)

“Zika” and You Will Find
This Week in Virology Podcast (2/7/2016)

Publications

The Placental Barrier

Organotypic Models of Type III Interferon-mediated Protection From Zika Virus Infections at the Maternal-fetal Interface
Corry J, Arora N, Good C, Sadovsky Y, and Coyne CB
Proceedings of the National Academy of Sciences of the U S A
2017 Aug 29

Type III Interferons Produced by Human Placental Trophoblasts Confer Protection against Zika Virus Infection
Bayer A, Lennemann NJ, Ouyang Y, Bramley JC, Morosky S, Marques Jr. E, Cherry S, Sadovsky Y, and Coyne CB
Cell Host & Microbe
2016 May 11

A Three-dimensional Culture System Recapitulates Placental Syncytiotrophoblast Development and Microbial Resistance
McConkey C, Delorme-Axford E, Nickerson CA, Kim KS, Sadovsky Y, Boyle JP, and Coyne CB
Science Advances
2016 Mar 4

Human Placental Trophoblasts Confer Viral Resistance to Recipient Cells
Delorme-Axford E, Donker RB, Mouillet JF, Chu T, Bayer A, Ouyang Y, Wang T, Stolz DB, Sarkar SN, Morelli AE, Sadovsky Y, and Coyne CB
Proceedings of the National Academy of Sciences of the U S A
2013 Jul 16

The Gastrointestinal Barrier

Enteroviruses Infect Human Enteroids and Induce Antiviral Signaling in a Cell-lineage Specific Manner
Drummond CG, Bolock, AM, Congrong M, Luke CJ, Good, M, and Coyne, CB
Proceedings of the National Academy of Sciences of the U S A
2017 Feb 14

A Three-dimensional Cell Culture Model to Study Enterovirus Infection of Polarized Intestinal Epithelial Cells
Drummond CG, Nickerson CA, and Coyne CB
mSphere
2015 Nov 18

RIP3 Regulates Autophagy and Promotes Coxsackievirus B3 Infection
Harris KG, Morosky SA, Drummond CG, Patel M, Kim C, Stolz, DB, Bergelson JM, Cherry S, and Coyne CB
Cell Host Microbe
2015 Aug 12

Cellular Pathways Targeted by RNA Viruses to Promote Their Replication

Dengue and Zika Viruses Subvert Reticulophagy by NS2B3-mediated Cleavage of FAM134B
Lennemann, NJ and Coyne, CB
Autophagy
2017 Feb

RIP3 Regulates Autophagy and Promotes Coxsackievirus B3 Infection
Harris KG, Morosky SA, Drummond CG, Patel M, Kim C, Stolz, DB, Bergelson JM, Cherry S, and Coyne CB
Cell Host Microbe
2015 Aug 12

BPIFB6 Regulates Secretory Pathway Trafficking and Enterovirus Replication
Morosky S, Lennemann NJ, and Coyne CB
Journal of Virology
2016 Apr 29

ADAP2 is an Interferon Stimulated Gene That Alters Virus Entry
Shu Q, Lenneman N, Sarkar SN, Sadovsly Y, and Coyne CB
PLoS Pathogens
2015 Sep 15

BPIFB3 Regulates Autophagy and Coxsackievirus B Replication Through a Noncanonical Pathway Independent of the Core Initiation Machinery
Delorme-Axford E, Morosky S, Bomberger J, Stolz DB, Jackson WT, and Coyne CB
MBio
2014 Dec 9

Opportunities to Join

We’d Like to Hear From You!

The Coyne Lab is looking for enthusiastic and talented students or postdocs interested in working with us. Please inquire to Dr. Coyne via email.