Kristian Dreij

Vital knowledge has been gained from studying driver mutations of cancer, but a few mutations in a limited number of genes cannot fully describe the complexity of carcinogenesis. The recent development of NGS has enabled the identification of genome wide mutational signatures and provided important insights into the underlying causes of human cancer. Although humans mainly are exposed to complex mixtures of agents contributing to cancer development, like air pollution and lung cancer, this research has entirely focused on single mutagens, which likely has impeded the application of mutational signatures in cancer research. The public health impact of understanding these associations is significant

identifying causes of cancer is essential for effective preventative interventions. Here, the aim is to determine mutational signatures of environmental complex mixtures using urban air PM samples and normal lung and liver cells. Mutational signatures will be determined by whole genome sequencing followed by somatic variant-calling, and the air PM samples have been collected in three cities differently impacted by emission sources. The signatures will be functionally validated by transcriptome gene expression analysis and association analyses between enriched pathways and mutational signatures. The proposed project comprises a novel approach by combining advanced NGS technology and environmental samples to establish the mutagenic impact of complex mixtures in cancer development.

Biomass burning is a global concern in terms of climate change, biological diversity, and health hazards. Globally, ca 3 billion people are exposed to biomass particulate matter (PM). Biomarkers of exposure and effect are fundamental for understanding environmental exposures, mechanistic pathways, and monitoring early adverse outcomes. Our aim is to assess the acute cardiopulmonary (CP) health effects due to short-term exposure to biomass PM among the population in Amazon deforestation arc together with in vitro analyses of sampled PM in a lung cell model to provide a mechanistic characterization of the health hazard. The project is based on a panel study in Amazon, with measurements of CP health and effect biomarkers using an exposure lag of 1-7 days during the wet and dry season with exposure assessment based on personal PM monitoring and urinary metabolites. The mode of action is assessed by in vitro studies using sampled PM. The project addresses the so far neglected and less understood issue of acute CP effects due to short-term exposure to PM from wildfires. This project will be the first of its kind to combine personal monitoring of exposure, specific CP biomarkers, and functional tests with mechanistic in vitro studies of collected PM in Amazon. How does this translate to public awareness? To reduce the gap between high-quality research and effectively engaging affected communities we will use environmental education strategies among the exposed population.

Air pollution, which include hazardous gases and particles, causes staggering economical losses and is the largest environmental health risk factor for disease and pre-mature death. Road traffic is a large source to particles, black carbon and hazardous polycyclic aromatic compounds, and is thought to be responsible for a substantial portion of the total pre-mature deaths caused by particles. Vehicular particle emissions comprise tail-pipe emissions, different wear particles and road dust re-suspension.Research on vehicular emissions is mostly conducted on a single vehicle or a single engine whose emissions are difficult to extrapolate to the diverse vehicle fleet actually running on the roads. To address this issue, this project will conduct sampling of collectively emitted traffic related PM10 and PM2.5 close to a heavily trafficked highway for the timespan of a whole year.The organic fraction present on the collected particles will be characterized using nontarget analytical chemical methods using complementary instrumental techniques to obtain a comprehensive chemical profile of the organic fraction emitted from vehicular traffic. Combined chemical analyses and in vitro assays will be made to identify health relevant traffic related organic chemical compounds.In order reduce the negative health impact from road traffic emissions it is of necessity to understand the composition of these emissions and the health risks associated with those emissions.