Toxicology of Environmental Mercury in Animal Development

Our overarching research interest is to gain understanding of the mechanisms by which fundamental cellular and molecular pathways in animal development become susceptible to perturbation by environmental agents. Our laboratory focuses on methylmercury (MeHg), a persistent organic form of mercury (Hg) that arises from both natural and anthropogenic sources and has a longstanding legacy as neurotoxicant. Within the global cycling of Hg in our environment MeHg is known to bioaccumulate in fish and seafood. Despite its unquestionable toxicity with high-level exposure, there remains considerable uncertainty in determining the risks associated with the background-level MeHg exposures commonly experienced today, predominantly via fish in the human diet.

Our overall approach is to investigate molecular, genetic and metabolic pathways responsible for the natural variation in tolerance and susceptibility to MeHg toxicity during development across a number of species. Our laboratory uses a wide range of methodologies including: transcriptomic and genomic screens together with functional assays of developmental toxicity in transgenic Drosophila (fruitflies); a gestational exposure model with subsequent molecular phenotyping and behavioral assessment in mice; kinetic and metabolic profiling of MeHg from fish meals in humans using longitudinal biomarkers and probing the gut microbiome.

We have made an important discovery that, in addition to neurons, myoblasts and developing muscle are susceptible MeHg toxicity targets. Also, signals within the Notch receptor pathway and polymorphisms in glutathione-related genes have proven to moderate MeHg toxicity. In a translational component of our research we are integrating our molecular-genetic analyses of MeHg related pathways in flies with studies of human cohorts as part of the Seychelles Child Development Study, a longstanding epidemiological study of prenatal MeHg exposure and child development based here at the University of Rochester for over 25 years.