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Our lab studies host–microbe interactions in the gastrointestinal tract through the activity-guided discovery of proteins, post-translational modifications, and metabolites that shape cell signaling at the molecular level.

Our primary goal is to understand how infection-associated oxidative stress influences host cell signaling and microbial adaptation to the host environment. We use a combination of chemical proteomics, genetics, and complex infection models to identify proteins that are oxidized during infection and determine how protein oxidation affects host–microbe interactions. In addition, we use mass spectrometry-based approaches to identify novel metabolites that may contribute to redox regulation in gastrointestinal bacteria. Our long-term goal is to uncover redox-signaling pathways and mechanisms of antioxidant defense that could be targeted to improve the diagnosis and treatment of diseases associated with pathogen-induced oxidative stress, including major gastrointestinal cancers.

In addition, we aim to develop new probes and antimicrobials for the precise detection and inhibition of disease-causing bacteria in the gut. The rapid diagnosis and treatment of bacterial infections is critical for controlling the spread of disease; however, selectively targeting bacterial pathogens within complex microbial communities, like those found in the human gut, remains a significant challenge. Our strategy harnesses the unique biochemical properties of pathogen proteases to selectively target pathogenic microbes in an infected host. We use genetic and biochemical methods to characterize the molecular processes that promote protease activation in the gut, and subsequently draw on these principles to design protease-specific biosensors and prodrugs that are specifically activated during infection.

By bridging the fields of chemistry and microbiology, we strive to develop new approaches that will increase basic understanding of host–microbe interactions and generate new leads for therapeutic targets, activity-based diagnostics, and drug-delivery systems.