About Us

The Center for Phage Biology & Therapy has informally existed at Yale since 2016 when we treated our first case of multidrug-resistant Pseudomonas aeruginosa with phage OMKO1. Since then, we’ve treated numerous infections with phage therapy, including prosthetic joint infections, lung infections, and even a sick sea turtle.

Over the years, we’ve formally established the Center with the generous funding of Yale University and philanthropic contributions from individuals who share our vision for phage therapy. Our goal is to provide the research, tools, and opportunity to develop phage therapy into a safe, effective, scientifically sound, and rational approach to infection control.

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Research

Phage biology research is crucial to understanding the terrestrial and aquatic biodiversity of earth’s most abundant microbes, and to elucidate how phage-bacteria ecological interactions shape natural communities and host microbiomes. We examine environmental samples (e.g., soils, freshwater, wastewater) to discover and characterize novel phages, which expand our biorepositories and knowledge of phage genomes and phenotypic traits. A major focus is to understand how phages exert selection pressure on host bacteria to evolve phage resistance and whether mutational changes alter the growth, virulence, antibiotic resistance, and other traits in bacterial pathogens. Results are presented in lectures to Yale School of Medicine and Yale School of Public Health students, used to create graduate rotation projects, and used to develop undergraduate courses.

Our team pioneered an innovative phage-based approach to address the antibiotic-resistance crisis: using phages that bind to specific bacterial virulence factors to kill these pathogens, while also selecting for surviving phage-resistant bacteria with reduced pathogenicity and/or decreased antibiotic resistance. This approach led to successful cases of emergent phage treatment in humans and past and upcoming clinical trials. Our ongoing efforts develop phages that target pathogenic bacteria important in human medicine and plant and animal agriculture, as well as phages used in diagnostics, environmental remediation, wastewater treatment, and hospital room disinfection.

By harnessing liquid-handling-robotics, microfluidics, and systems-biology approaches, we aspire to develop methods for high-throughput phenotyping of phage traits, mathematical approaches for theoretically predicting phage-bacteria evolutionary interactions, computational data-science methods for “big-dataset” analyses of microbial genomics and phenotypic traits, and artificial-intelligence and computer science approaches to predict phage host-ranges, bacterial susceptibility to phage infection, and phage-bacteria interactions with host microbiomes.

Our emergency and compassionate use phage therapy has been safely and effectively administered to patients, especially to target multidrug and pandrug-resistant bacteria infesting indwelling medical devices, and to treat pulmonary infections of individuals with cystic fibrosis (CF), non-CF bronchiectasis, and chronic-obstructive pulmonary disease (COPD). We conduct translational research on existing and candidate therapeutic phages using in vivo models and in vitro cell-biology systems. In addition, we analyze bio-banked samples isolated from patients before, during, and after phage treatment to examine changes in phage-bacteria coevolution, microbial metagenomics, transcriptomics, and human immunobiology. Our murine models are used to study how phage therapy can be administered to treat lung inflammation, pneumonia, sepsis, and joint and skin infections. Additionally, we employ animal models of left-ventricular-assist devices, diabetic wounds, catheter-associated urinary tract infections, and diarrheal diseases.

We currently develop personalized treatment of bacterial infections using innovative phage therapy and will continue to pursue related clinical trials that will ensure broad patient access to therapy, regardless of socioeconomic status. We conduct clinical research on interactions between phages in our biorepository with strains of bacterial pathogens that are sampled from patients, especially those with CF, non-CF bronchiectasis, COPD, pneumonia, and post-COVID-19 pneumonia. A key focus is analysis of longitudinal patient samples to reveal details of altered virus-cell phenotypic interactions, phage and bacterial genomics, microbiome composition, microbial community metagenomics, and transcriptomics within treated humans over time—before, during and after phage therapy.