Superfund Research Program
Mapping Proteome-Wide Reactivity of Superfund Chemicals Using Chemoproteomic Platforms
Many hazardous chemicals at Superfund sites have been linked to adverse health effects, but their toxicological mechanisms remain poorly understood. The project uses innovative chemical technologies to dissect and simplify the complexities associated with analyzing the toxicological mechanisms associated with exposure to chemical mixtures and the Exposome. The researchers have developed a chemoproteomic strategy termed activity-based protein profiling (ABPP), which uses reactivity-based probes to identify direct protein targets of SRP chemicals. In the second year of this project, the researchers used chemoproteomic profiling approaches to map the proteome-wide reactivity of monomethylarsenous acid (MMA III), benzene, naphthalene, and benzopyrene and their metabolites in vivo in mice. In the third year, they have been characterizing the functional consequences of these chemicals targeting their respective protein targets. The data from these studies reveal new mechanisms of toxicity associated with arsenic exposure and help to potentially explain how MMA III exerts toxicological effects in humans.