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Projects

Identification & Characterization of Methylmercury (MeHg) Tolerance and Susceptibility Genes and Pathways

Identification & Characterization of Methylmercury (MeHg) Tolerance and Susceptibility Genes and PathwaysWe are actively engaged in unbiased whole-genome screens using the Drosophila (fruit fly) model to identify novel candidate genes and pathways that function in development and moderate MeHg toxicity. Using a transcriptomic approach we have resolved a role for Phase I metabolism genes of the Cytochrome P450 (CYP) family as tolerance genes in MeHg toxicity. The strongest candidate, Drosophila CYP6g1, is the homolog of human CYP3A genes (CYP3A4, 3A5, and 3A7), which are the foremost xenobiotic metabolizing enzymes in the human liver.

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Functional Assessment of Genetic Factors that Moderate Methylmercury (MeHg) Toxicity in Humans

Functional Assessment of Genetic Factors that Moderate Methylmercury (MeHg) Toxicity in HumansGlutathione (GSH) is a major first line of defense against MeHg toxicity. Several genes are involved in the synthesis and metabolism of GSH, which, in the realm of MeHg metabolism, we refer to collectively as the “GSH axis”. Both direct and indirect activities of this small molecule thiol compound are implicated in offsetting MeHg toxicity.

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The Drosophila Embryo as a Small Molecule Toxicity Assay Platform

The Drosophila Embryo as a Small Molecule Toxicity Assay PlatformIn an effort to optimize our assays of MeHg toxicity we have innovated a method for routine pharmacological application of small molecules (i.e. drugs and toxins) to the developing Drosophila embryo, a premier model of developmental biology. We have exploited this system for both phenotype characterization and for gene discovery in the context of MeHg toxic exposures.

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