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Pairing adverse outcome pathway discovery with advances in gene editing to solve toxicity mechanisms (SOT 2021)
Citation:
Wehmas, L., T. Tal, M. Russo, D. Gorelick, AND L. Zhang. Pairing adverse outcome pathway discovery with advances in gene editing to solve toxicity mechanisms (SOT 2021). Society of Toxicology 2021 Symposium, Orlando, FL, March 12 - 26, 2021.
Impact/Purpose:
Symposium proposal abstract submitted to the Society of Toxicology Annual meeting March 2021. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 gene editing promises to revolutionize our understanding of both fundamental biology and the adverse effects of chemical exposure. This symposium will provide cutting edge examples of how researchers are applying CRISPR/Cas-9 to causally reveal key molecular events resulting from chemical exposure across multiple disciplines of toxicology. Presentations will focus on environmental chemicals and combine ‘omics’-based pathway discovery with gene editing in cell and zebrafish model systems. Overall, attendees will encounter specific examples of CRISPR/Cas9 use in the fields of neurotoxicity, carcinogenicity and occupational safety, and endocrine toxicity that show advances in adverse outcome pathway/network discovery.
Description:
While gene editing technologies such as RNAi, transcription activator-like effector nucleases, and zinc finger nucleases have been in use for years, none offer the ease of use and specificity of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 approaches to advance our understanding of both fundamental biology and the adverse effects of chemical exposure. Forward and reverse genetic approaches can be applied across in vitro and multiple in vivo model systems for an unprecedented understanding of conserved modes of toxicity, potential susceptibility, and impacts on human and environmental health. This presentation will provide cutting edge examples of how researchers are applying CRISPR/Cas-9 to characterize effects of gene edits and ultimately causally reveal key molecular events resulting from chemical exposure across multiple disciplines of toxicology. Presentations will focus on environmental toxicants and combine ‘omics’-based pathway discovery with gene editing in cell and zebrafish model systems. In addition, innovative applications relevant to toxicity testing will be explored including CRISPR-mediated genome wide cell knockouts for rapid chemical toxicity screening and novel mode of action discovery to hypothesis driven loss-of-function edits in the zebrafish model to validate the essentiality of key molecular targets in diverse adverse outcome pathways or disease states. Overall, attendees will encounter novel case studies in the domains of neurotoxicity, carcinogenicity and occupational safety, and endocrine toxicity that collectively demonstrate unparalleled advances in adverse outcome pathway/network discovery facilitated by gene editing technologies. This abstract does not reflect US EPA policy.