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Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Staff Scientist Mariona Bustamante, Barcelona Institute for Global Health - ISGlobal, Spain
- Second opponent: Researcher Ståle Nygaård, Cancer Registry of Norway,
- Third member and chair of the evaluation committee: Professor Jahn Frederik Frøen, University of Oslo
Chair of the Defence
Associate Professor Johanne Egge Rinholm, University of Oslo
Principal Supervisor
Professor Stine Marie Ulven, Universitetet i Oslo
Summary
Air pollution is a major contributor to global disease burden. Key pollutants include particulate matter and gaseous compounds. Exposure to natural green and blue spaces may mitigate the harmful effects of air pollutants. Environmental pollutants can alter gene expression by regulating transcription factors. The aryl hydrocarbon receptor (AHR) is a nuclear receptor activated by organic pollutants such as TCDD. AHR is also modulated by dietary ligands, including activation by 3,3’-diindolylmethane (DIM) and inhibition by resveratrol.
In Paper I, we investigated genome-wide AHR binding and gene expression regulation after treatment with TCDD, E2, DIM, and resveratrol. Both TCDD and DIM activated AHR; however, DIM-induced AHR binding was enriched at estrogen response elements and regulated developmental genes, whereas TCDD primarily affected metabolic genes. These findings highlight that distinct environmental exposures can differentially regulate AHR activity, to influence chronic disease risk.
Papers II and III examined associations between air pollution, natural spaces, and gene expression in population-based children and adult cohorts. In children, PM2.5 exposure was associated with expression levels of 86 genes (FDR < 0.25), including GFI1B, TSC22D1, and GNG11. Gene set enrichment showed negative associations between PM2.5 and interferon alpha and gamma pathway genes. In adults, the exposure to PM2.5 was also associated with the expression of the highest number of differentially expressed genes. Negatively associated genes were enriched for cell cycle, DNA repair, and metabolism as well as oxidative phosphorylation. Green space within 300 meters of residence was negatively associated with adaptive immune response genes in both child and adult cohorts.
Overall, PM2.5 showed the most consistent gene expression associations across age groups. Green space may exert protective effects through modulation of immune gene expression. Additionally, dietary ligands can directly regulate pollutant activated transcription factors such as AHR.
Additional information
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