This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Adverse health effects from exposure to dioxin-like compounds are in part mediated through activation of aryl hydrocarbon receptors (AHR), induction of genes encoding biotransformation enzymes, and dyregulation of numerous genes outside the toxic response pathway. AHR proteins have non-transcriptional roles in cell physiology in the absence and presence of AHR ligands. Thus, it is difficult to distinguish AHR-dependent toxic response mechanisms from the perturbation of endogenous function of AHR. We study the divergence of function among multiple AHR paralogs in early vertebrates so we may separately test the pleiotropic functions of the single mammalian AHR. Our previous studies support that shark AHR paralogs diverge in function. In the current study, several undergraduate student projects are designed to assess the function of shark receptors in cell physiology, development, and toxic responses to AHR agonists, and to investigate the genomic context of these early vertebrate AHR genes with a BAC library.
We aim to develop an effective paradigm to separately test hypotheses about subsets of mammalian AHR gene targets and non-transcriptional AHR protein function. Results from our research will provide information relevant to human physiology, development, and environmental health.
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