Excellence in research: polycomb-RNA granule crosstalk during 6PPD-quinone stress in human lung epithelial cells

The National Science Foundation Office of Integrative Activities awarded Southern University and A & M College $893,779 on September 1, 2026, under the Integrative Activities program (CFDA 47.083) to investigate how 6-PPD quinone, a tire-wear environmental contaminant, disrupts molecular processes in human lung epithelial cells, specifically examining the interaction between polycomb repressive complexes and RNA-regulating cellular structures such as stress granules and processing bodies.

The project runs through August 31, 2029, with performance at the Scotlandville, Louisiana campus. The collaborative work involves Grambling State University as a research partner. Beyond the primary research objective, the award funds development of research infrastructure, interdisciplinary research training for undergraduate and graduate students, establishment of a pathway from undergraduate education at Grambling State University to doctoral training in environmental toxicology at Southern University, and K-12 STEM outreach activities. The project advances fundamental understanding of how environmental contaminants influence RNA regulation and epigenetic control, providing a scientific foundation for predicting biological effects of emerging contaminants and supporting capacity building in environmental molecular science at an HBCU and 1890 land-grant institution.

Abstract

Tire wear is an increasingly important source of environmental pollution, releasing chemicals that are widely distributed in the environment. One such chemical, 6-PPD quinone (6-ppdq), is a recently identified transformation product of a common tire additive that has emerged as an environmental contaminant of concern because of its widespread occurrence and documented biological effects across multiple experimental systems. However, the mechanisms underlying these responses remain poorly understood. This collaborative project between southern university and a & m college and grambling state university will investigate how 6-ppdq disrupts the molecular processes that enable cells to respond and adapt to environmental stress. By advancing fundamental understanding of how environmental contaminants influence RNA regulation and epigenetic control, the project will expand knowledge in environmental molecular science and provide a scientific foundation for predicting the biological effects of emerging contaminants. The project will also strengthen research infrastructure, provide interdisciplinary research training for undergraduate and graduate students, establish a pathway from undergraduate education at grambling state university to doctoral training in environmental toxicology at southern university, and engage k-12 students through stem outreach activities. Through these integrated research and educational activities, the project will promote scientific discovery, develop a highly skilled stem workforce, and support the nation's capacity for innovation and environmental research. The project will investigate how 6-ppdq alters the coordinated activities of stress granules and processing bodies, two cellular structures that regulate RNA processing during cellular stress, and how these structures interact with polycomb repressive complexes, which regulate gene activity through epigenetic mechanisms. The investigators will determine how these interactions influence RNA metabolism, protein synthesis, and epigenetic regulation in human lung epithelial cells using advanced molecular biology, high-resolution imaging, transcriptomics, proteomics, and integrated computational analyses, including computational modeling, molecular dynamics simulations, and density functional theory. These complementary experimental and computational approaches will establish a mechanistic framework for understanding how environmental contaminants disrupt interconnected RNA regulatory and epigenetic networks. The project will generate foundational knowledge of cellular stress-response mechanisms, identify molecular signatures associated with contaminant-induced cellular perturbations, and develop broadly applicable experimental and computational strategies for investigating the molecular actions of emerging environmental contaminants. By integrating computational modeling and data-driven analyses with experimental biology, the project will strengthen interdisciplinary research and advance computational approaches for understanding complex biological systems. Through hands-on research and mentoring, the project will establish a strong stem workforce pipeline by preparing undergraduate and graduate students for advanced education and careers in academia, industry, biotechnology, and government. This project advances NSF?s priorities in biotechnology. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the foundation's intellectual merit and broader impacts review criteria.- subawards are planned for this award.