Research

Human exposure to tens of thousands of chemical contaminants (the human “exposome”) occurs continually through air, drinking water, food, and dermal contact. Exposure to these chemicals has been linked to increasing rates of chronic disease, yet most compounds remain uncharacterized in terms of their toxicity and biological activity. With the number of chemicals in commerce (>350,000) continuously growing, the risk of their exposure to humans necessitates a comprehensive understanding of their health implications.

Research in the Barrett group aims to answer two central questions:

What bioactive contaminants are present in the biological matrices (e.g., blood, serum) of diseased versus healthy humans?
What roles do these contaminants play in driving human disease at the mechanistic, molecular, and population levels?

To address these questions, our group applies a multi-pronged, integrative framework that bridges analytical chemistry, exposomics, chemical biology, and toxicology. By combining discovery-based approaches with mechanistic follow-up, we aim to move beyond detection toward causal understanding.

Our core toolkit includes:

Non-targeted high-resolution mass spectrometry
Exposomics and other multi-omics approaches
Protein affinity–guided pulldown methods
Chemical biology techniques
in vitro, in silico, and in vivo toxicological assays

Together, these approaches enable the discovery of previously unknown bioactive environmental chemicals and the elucidation of their molecular targets and health impacts.

Non-Targeted Exposomics

Exposomics is the comprehensive study of all environmental exposures across the lifespan and their relationships to health and disease. Unlike traditional targeted monitoring, exposomics does not presuppose which chemicals are important, allowing unexpected and emerging contaminants to be discovered.

Nontargeted analysis (NTA) uses high-resolution mass spectrometry to detect thousands of chemical features simultaneously, without prior knowledge of their identity. This approach is essential for interrogating the “dark exposome”: chemicals that are present in humans but absent from regulatory or toxicological databases.

Chemical-Protein Interactions and Disease

Identifying chemicals in humans is only the first step. To understand how exposures contribute to disease, we must determine what those chemicals do biologically.

Our lab uses protein affinity–guided pulldown approaches to identify interactions between environmental chemicals and human proteins. In these experiments, bioactive compounds are used as “bait” to capture their protein targets from complex biological mixtures.

This strategy allows us to identify molecular targets of environmental contaminants, link exposure to specific biological pathways, and prioritize chemicals based on mechanistic relevance, not just abundance.

By mapping chemical–protein interactions, we bridge the gap between exposure and disease mechanism.

in vitro, in silico, and in vivo Toxicology

To translate chemical discovery into health insight, we integrate multiple levels of toxicological assessment:

In vitro assays to assess receptor activation, pathway disruption, and cellular toxicity
In silico modeling to predict binding, bioactivity, and toxic potential
In vivo studies to evaluate organism-level effects and environmentally relevant outcomes

This integrated approach enables us to move from unknown chemical → biological activity → mechanistic understanding → health relevance, providing a framework for evidence-based chemical prioritization.

By combining exposomics, chemical biology, and toxicology, the Barrett research group aims to uncover hidden drivers of chronic disease and provide mechanistic insight into how environmental exposures shape human health. Our work supports improved risk assessment, informs regulatory decision-making, and advances a more comprehensive understanding of the human exposome.

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