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Explore Our Research
PHAGE THERAPY & ANTIMICROBIAL RESISTANCE
The rise of multidrug-resistant bacteria is creating an urgent need for alternatives to conventional antibiotics. We investigate how bacteriophages, the viruses that infect bacteria, can be harnessed as precision antimicrobial agents. Rather than viewing bacterial evolution simply as an obstacle to therapy, our research seeks to anticipate and exploit it by identifying phage combinations that broaden host range, constrain the evolution of resistance, and work synergistically with antibiotics.
Our work spans fundamental phage-host biology through preclinical therapeutic development. We have investigated phage treatment of Mycobacterium tuberculosis in humanized mouse models, phage-antibiotic combinations against multidrug-resistant Staphylococcus aureus, and the effects of phages and antibiotics on biofilm-forming bacterial populations.
A major current focus is multidrug-resistant Klebsiella pneumoniae, an important cause of pneumonia and other healthcare-associated infections. We are developing evolution-guided phage cocktails designed to remain effective against diverse clinical isolates, persister cells, intracellular bacteria, and phage-resistant mutants. By combining experimental evolution, genomics, host-range screening, phage-antibiotic synergy testing, and models of infection, we aim to understand not only whether a therapy works, but how bacteria and phages evolve during treatment.
We are also working toward practical delivery of phage therapeutics. In collaboration with pharmaceutical scientists, we are developing stable, respirable dry-powder formulations that could deliver phages directly to the lung while reducing dependence on cold-chain storage. Together, these studies seek to transform phage therapy from a reactive search for a phage that kills a pathogen into a predictive, evolution-informed strategy for treating antibiotic-resistant infections.
VIRUS EVOLUTION & COLLECTIVE TRANSMISSION
We investigate how rotaviruses generate diversity, interact with one another, and exploit host cells to enhance transmission. Our work examines how processes such as recombination, genome-segment organization, coinfection, and collective transmission shape viral evolution and influence the ability of viruses to spread through host populations.
A major focus of our current research is the discovery that rotaviruses can leave infected cells non-lytically within host-derived extracellular vesicles. Rather than transmitting exclusively as individual mature virions, rotaviruses can be released in membrane-bound microvesicles that carry multiple viral particles and other biologically active molecules. This mode of transmission creates a fundamentally different infection environment in which multiple viral genomes may enter a recipient cell together and interact from the earliest stages of infection.
We are investigating the evolutionary and functional consequences of this collective transmission strategy. Our work asks whether vesicle-associated transmission increases viral fitness, promotes coinfection and genetic exchange, broadens cell tropism or host range, and helps viruses evade host immune defenses. We are also studying how viral molecules carried within extracellular vesicles modify recipient cells, including the potential role of viral microRNAs in regulating host immunity and promoting viral replication and assembly.
Together, these studies seek to understand how collective transmission changes the basic unit on which viral evolution acts. Instead of viewing infection solely as competition among individual virus particles, our work explores how groups of viruses can travel together, interact within cells, and alter their local environment in ways that influence viral diversity, transmission, and evolutionary success.
BACTERIOPHAGE LIFE HISTORIES AT THE SINGLE-CELL LEVEL
We use bacteriophages as model systems to investigate how natural selection shapes viral life-history strategies at the level of individual infected cells. A central question is how phages balance the competing demands of rapid reproduction and maximizing the number of offspring produced before host-cell lysis.
Using bacteriophage λ, we have shown that viral fitness is maximized at an intermediate lysis time, reflecting a fundamental tradeoff between reproducing quickly and allowing sufficient time to produce a larger burst of progeny. We combine experimental evolution, quantitative microbiology, single-cell measurements, and mathematical modeling to determine how these life-history traits respond to ecological conditions and selection.
We are particularly interested in the role of biological noise. Viral infections that appear identical at the population level can produce strikingly different outcomes in individual cells. Our work has revealed substantial cell-to-cell variation in both the timing of lysis and the number of phage particles produced. We investigate how stochastic gene expression generates this variation and how regulatory mechanisms can tune not only the average timing of a cellular event, but also its precision.
By connecting molecular regulation within individual cells to population-level viral fitness, this work seeks to explain how apparently noisy infection processes become evolutionarily optimized. More broadly, we use bacteriophages to understand how viruses evolve strategies for when to reproduce, how much to invest in each infection, and how much variation among individual infections can be tolerated or even favored by natural selection.
These questions also have direct relevance to phage therapy. Therapeutic efficacy depends not simply on whether a phage can infect a bacterial strain, but on how rapidly and reliably it reproduces within individual cells, how many progeny are produced, and how these traits vary across bacterial physiological states and environments. A quantitative understanding of phage life histories can therefore help identify phages with favorable growth characteristics, improve the design of therapeutic cocktails, and predict how phage populations will perform and evolve during treatment. In this way, our fundamental work on single-cell phage biology provides a mechanistic foundation for developing more effective and evolutionarily robust phage therapies.
MICROBIAL ECOLOGY & BIOFILMS
Bacteria rarely experience the uniform, nutrient-rich conditions of standard laboratory cultures. In natural environments and during chronic infections, they often live in spatially structured communities called biofilms, where nutrient availability, population density, physiological state, and interactions with other organisms can dramatically alter bacterial growth and susceptibility to antimicrobial treatments.
We study how these ecological conditions shape the formation, persistence, and resilience of bacterial biofilms. To investigate these processes under controlled but dynamic conditions, we developed a chemostat-based model that allows biofilms to grow while nutrients and other environmental variables are continuously manipulated. This system makes it possible to follow biofilm development over extended periods and to examine how microbial populations respond to changes in resource availability and other ecological stresses.
A major focus of this work is understanding why biofilm-associated bacteria can be difficult to eradicate. We examine how nutrient limitation and differences in bacterial physiological state influence responses to antibiotics and bacteriophages, and how biofilm structure affects the ability of these antimicrobial agents to control bacterial populations. We are particularly interested in the ecological and evolutionary processes that allow populations to persist, recover, or evolve following treatment.
By studying antimicrobial activity in dynamic microbial communities rather than exclusively in well-mixed planktonic cultures, we aim to develop a more realistic understanding of treatment efficacy. Ultimately, this work connects fundamental microbial ecology with the challenge of controlling persistent and antibiotic-resistant infections, helping identify environmental conditions and treatment strategies that can make resilient bacterial populations more vulnerable to intervention.
More broadly, this research asks how spatial structure, resource limitation, and ecological interactions reshape the evolutionary trajectories of bacterial populations. Understanding these processes can reveal why some microbial communities collapse under treatment while others remain stubbornly persistent.