Toxicology in the 21st Century Program (Tox21) - Genomic Toxicology

National Center For Advancing Translational Sciences

Investigators

Linked publications & trials

Abstract

The Tox21 Program is a multiagency collaborative effort among the Environmental Protection Agency (EPA), Food and Drug Administration (FDA), the National Toxicology Program (NTP) at the National Institute of Environmental Health Sciences (NIEHS), and NCATS to advance in vitro toxicological testing. The Tox21 Program is comprised of three NCATS teams: Systems Toxicology, Genomic Toxicology, and Computational Toxicology. The Genomic Toxicology group develops improved human cell culture models and methods to illuminate toxicology and human diseases. For example, we are collaborating with the NIEHS Cardiovascular Health Effects Innovation Team to evaluate twelve suspected cardiovascular toxicants for adverse effects on heart and vasculature. Methods: My lab is using primary human endothelial cell models and co-culture vascular models to elucidate how environmental toxicants and drugs cause vascular toxicity and heart attacks through impacts on vascular failure modes. Vascular failure modes include perturbations of vasoactivity, coagulation, inflammation, and atherosclerosis. My lab is characterizing these response mechanisms using cytotoxicity assays, cytokine profiling and transcriptomics coupled with Point of Departure (POD) analyses. Dr. Zhi-Bin Tong continues to advance neurotoxicity studies in my lab by publishing that our LUHMES immortalized human dopaminergic neuron model is uniquely vulnerable to ferroptotic cell death as well as perturbations to glutathione metabolism and iron metabolism (Tong 2022). In order to screen libraries for these neuronal vulnerabilities we engineered a LUHMES MT1G::Luciferase reporter cell line and established a 3D culture format in 1536 well microplates. This model will enable screening chemical libraries to identify neurodegenerative toxicants that may cause Parkinsons disease or other neurodegenerative diseases.