Bio: Dr. John Pierce Wise is the head of the Wise Laboratory for Environmental and Genetic Toxicology at the University of Louisville. Dr. Wise’s research focuses on understanding how environmental toxicants affect health and cause cancer from a One Environmental Health perspective considering cellular and molecular mechanisms in both humans and wildlife, with a particular emphasis on lung cancer and chromosome instability and translating those mechanisms and outcomes to organisms and populations. Dr. Wise’s work has been featured in local, national and international press and social media sites. The Society of Toxicology (SOT) featured a short film about his work (YouTube: https://youtu.be/8tYYQvehl2I?si=x0aE0Wt7Tpp49Xg_). He is a multi-award-winning scientist recognized by multiple scientific societies and universities. Dr. Wise holds a B.S. with distinction and with recognition in biology from George Mason University and a Ph.D. in pharmacology from George Washington University with postdoctoral training focused in from the National Cancer Institute (NCI), followed by training in occupational health and risk assessment at Jonathan Borak and Company. He served on the faculty of Yale University’s School of Medicine and School of Public Health, the University of Southern Maine, prior to joining the faculty at the University of Louisville, School of Medicine.
Abstract: Hexavalent chromium [Cr(VI)] is a well-established metal lung carcinogen, with widespread occupational and environmental exposure, however, its carcinogenic mechanisms are poorly understood. Chromosome instability is considered a driving mechanism for Cr(VI)-induced lung cancer lung cancer, yet how Cr(VI) causes chromosome instability is unclear. For structural chromosome instability, Cr(VI)-induced DNA double strand breaks are the key underlying lesion. These breaks only occur in late G2/S phases of the cell cycle, and consequently homologous recombination repair is the predominant repair pathway to protect against them. We focused on RAD51, the key effector protein in homologous recombination repair, and found Cr(VI) impacts RAD51 localization, structure, function, protein levels and RNA levels. Moreover, we have translated these effects across different human lung cell lines, across cell lines from different species and across model systems from cell cultures to rodent models and to human lung tumors. The data show across models that hexavalent chromium dysregulates DNA repair targeting both RNA and protein resulting in chromosome instability. This work was supported by NIEHS grant (JPWSr).
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Date | Time | Local Time | Room | Forum | Session | Role | Topic |
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2025-10-18 | 14:40-15:05 | 2025-10-18,14:40-15:05 | Room 2 - Guobin Hall 2 | Symposium Program (Session) |
Session 28: RNA Dysregulations and Environmental Carcinogenesis |
Speaker | Mechanisms of environmental carcinogenesis: how hexavalent chromium induces DNA repair dysregulation targeting RNA and protein |