Comparative toxicogenomics to determine conserved genetic and environmental interactions in craniofacial birth defects

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Project Summary Craniofacial dysmorphologies are among the most common human birth defects. The multifactorial basis of human birth defects has hindered identification of culpable genes and toxicants. Environmental exposures occur in mixtures, and genetic variation can sensitize embryos to these mixtures. This proposal uses bioinformatics and high-throughput analyses to predict and characterize multifactorial interactions in birth defects using zebrafish and mice. The aims of this proposal are: (1) Define synergistic interactions between environmental toxicants; (2) Model and characterize gene-environment interactions; (3) Test human disease relevance and evolutionary conservation. This approach leverages my expertise in zebrafish and mouse developmental toxicology to rapidly and efficiently gain insights into the most important unanswered questions surrounding birth defect etiology. The studies proposed will provide a direct avenue for prevention through risk communication of novel environmental and genetic risk factors.