Project 3 – Mitochondrial and Cellular Mechanisms of Neurotoxicity of Superfund Chemical Co-Exposures

Project Leaders

Trainees

Goals and Importance of Research

Some developmental exposures impact the proper functioning of mitochondria, resulting in altered behavior and increased risk of neurodegeneration and related diseases. This project will study the underlying mechanisms of developmental neurotoxicity from co-exposures to polycyclic aromatic hydrocarbons (PAHs) and the metals lead and cadmium in the nematode worm C. elegans. One plausible mechanism is that exposures change how neurons develop, leading to altered cell fate, structure, and connectivity (“hardwiring”). An alternative mechanism is that epigenetic changes result in altered function of neurons that otherwise look normal (epigenetic “programming”). This work will study these potential mechanisms, thus informing adverse outcome pathways and methods to intervene and reverse health impacts.

Novel Aspects of Research

• Take advantage of invariant and well understood developmental trajectory of the nervous system in C. elegans to detect changes to cell architecture after pollutant exposure.
• Test for sex specificity in mitochondrial and neuronal toxicity.
• Create innovative cell-specific tools to assess mitochondrial dysfunction in C. elegans.

Project Aims

1. Test if co-exposures to PAHs and the metals lead and cadmium cause developmental and later-life neurotoxicity by altering hardwiring.
2. Test if co-exposures cause developmental and later-life neurotoxicity via altered programming.

PROJECT 3 RECENT PUBLICATIONS

Faroud Lopez, R., Huayta, J., Williams, G. D. Z., Seay, S. A., Lalwani, P. D., Bacot, S. N., et al. (2025). Lithium nickel manganese cobalt oxide particles cause developmental neurotoxicity in caenorhabditis elegans. Environmental Science.Advances, 4(11), 1767–1781. doi:10.1039/d5va00103j

Huayta, J., Seay, S., Laster, J. 3., Rivera, N. A. J., Joyce, A. S., Ferguson, P. L., et al. (2025). Assessment of developmental neurotoxicology-associated alterations in neuronal architecture and function using caenorhabditis elegans. Altex, 42(4), 591–609. doi:10.14573/altex.2501151

Lalwani P, King D, Morton K, Rivera NA, Huayta J, Hsu-Kim H, Meyer J. Increased cytotoxicity of Pb2+ with co-exposures to a mitochondrial uncoupler and mitochondrial calcium uniporter inhibitor. Environmental Science: Processes and Impacts. 2023 July 21. PMCID: PMC10681630.

Shahid, S., Klein, C., Meyer, J., & Huayta, J. (2025). Glowing worms: A low-cost fluorescence kit for toxicological education using C. elegans. Retrieved from https://micropublication.org/static/pdf/micropub-biology-001506.pdf

Project 3 News