Faherty Lab: Christina Faherty, PhD

Overview

The focus of the Laboratory of Christina Faherty, PhD, at Massachusetts General Hospital is enhancing our understanding of gastrointestinal bacterial pathogens, particularly the Shigella species.

Shigella causes a significant global health burden each year by causing millions of infections predominantly in children under the age of five years in developing countries. Children subjected to recurrent diarrhea in developing countries often exhibit environmental enteropathy, a condition defined by severe damage to the gastrointestinal tract that typically results in delayed growth and development. There is still no effective vaccine against Shigella, antibiotic resistance is complicating disease treatment, and foodborne infections in industrialized nations are on the rise.

While many aspects of Shigella colonic cell invasion and intracellular survival are known, crucial gaps in knowledge remain that have hindered successful vaccine development. To cause infection in the colon, Shigella must transit the majority of the gastrointestinal tract and survive detrimental conditions such as a low pH in the stomach and bile in the small intestine. We seek to understand how Shigella alters gene expression during host transit and to determine how the bacteria recognize the colonic environment to initiate infection. By focusing on these processes, we will understand the early events in Shigella infection and identify unique virulence factors to target for vaccine development. Our work has enabled us to expand the Shigella infection paradigm and demonstrate the importance of utilizing in vivo stimuli to mimic host transit in our research.

In all, we have a better understanding of Shigella pathogenesis that could finally translate to successful vaccine candidates and improve the health of millions of people around the globe.

Research Projects

Identify the adherence factors utilized by Shigella to initiate contact with the colonic epithelium

Our previous work demonstrates that S. flexneri exposure to bile salts induces the expression and outer membrane localization of OspE1 and OspE2, two proteins that function as adhesins to initiate host cell contact.

We are currently expanding our work with OspE1 and OspE2 as well as determining if other adherence factors are utilized by the bacteria.

This work uses novel models of the human gastrointestinal tract to facilitate characterization and discovery of adherence factors.

Understand the gene expression profile during host transit

We are currently utilizing various host signals to understand Shigella survival and how virulence factors are expressed during gastrointestinal transit.

Given the efficient invasion mechanism of Shigella, we hypothesize that host factors serve as important signals to optimize virulence gene expression at key points prior to colonic epithelial cell contact.

We are also expanding our analyses to clinical isolates of Shigella to compare the various Shigella species, investigate if differences in virulence explain epidemiological infection patterns around the globe and determine if a multivalent vaccine can be developed.

With collaborators at Massachusetts Institute of Technology (MIT), we are designing and engineering bacteriophage viruses that will target and kill Shigella and other enteric pathogens while leaving friendly commensal bacteria unharmed.

It is our hope that phage therapy will become a viable alternative to antibiotics and enhance treatment for environmental enteropathy.

News & Events

• Novel models for enteric infections—an interview with the Faherty Lab
• Bile salt-induced biofilm formation in enteric pathogens: techniques for identification and quantification
• Harmful bacteria survive perilous path through the gut with help from an unlikely source
• CDC notes Shigella strains with reduced susceptibility
• Shigella investigators in Michigan bring in help from the CDC
• Shigellosis outbreak at elementary school kept quiet for weeks
• Multidrug-resistant Shgellosis: An Emerging Sexually Transmitted Infection
• Outbreak sickens 167 in Dubuque County, Iowa
• Galveston county officials mark rise in gastrointestinal illness

Lab Members

Principal Investigator

Christina S. Faherty, PhD
Assistant Molecular Biologist, Massachusetts General Hospital
Assistant Professor of Pediatrics, Harvard Medical School

Research Team

Alumni

Kourtney Nickerson, PhD: Charles River Laboratories
Rachael B. Chanin: Currently enrolled in a PhD program at the University of Texas Southwestern Medical Center
Alejandro Llanos-Chea, MD: Assistant Professor of Pediatrics at the University of Miami, Miller School of Medicine

Publications

View full publication list