Developmental Neurotoxicity of Environmental Mercury
My research interests are deeply rooted in understanding the molecular mechanisms of how environmental factors impact neural development. Our laboratory is therefore focused on investigations of the environmental neurotoxin methylmercury (MeHg). We have long understood from historic accidental MeHg poisonings in Japan and Iraq that the fetal nervous system is the preferred target for MeHg toxicity and that permanent neurological deficits can result from prenatal MeHg exposure. Widespread human exposure to MeHg persists in today’s society, largely originating from mercury released in fossil fuel emissions and culminating with the intake of dietary fish that has bio-magnified MeHg from the environment. Despite its unquestionable toxicity, there remains considerable uncertainty in determining the risks associated with MeHg exposure, which has propagated controversy over the harm versus benefit of fish in the diet. Our studies are therefore pointed at addressing a priority concern for human health. At the same time, we are seeking a deeper understanding of fundamental mechanisms of neural development and their vulnerability to environmental insult.
Our investigations use a unique combination of methods of toxicology and molecular genetics based in a premier model of developmental biology: Drosophila melanogaster (the fruit fly). Our overall approach is one of gene discovery and functional validation. We are discovering novel genes and pathways that influence developmental toxicity of MeHg through methods of whole genome screening and bioinformatics. In parallel, we are characterizing newly and previously identified MeHg tolerance and susceptibility genes in the context of whole animal development using transgenic flies. We are invoking a translational component to our research through integrated genetic analyses of several conserved genes in humans by probing DNA samples from the Seychelles Child Development Study, a longstanding cohort study of MeHg and development based at the University of Rochester.
Current Research Projects
- Target organ specific activity of drosophila MRP (ABCC1) moderates developmental toxicity of methylmercury. Toxicol Sci. 140, 425-35. (2014 Aug 01).
- The Notch target E(spl)mδ is a muscle-specific gene involved in methylmercury toxicity in motor neuron development. Neurotoxicol Teratol. 43, 11-8. (2014 Jun 03).
- A method of permeabilization of Drosophila embryos for assays of small molecule activity. J Vis Exp. In press. (2014 Jan 01).