Research outline
Dreij's lab aims to shift the focus from studying the toxic effects of single chemicals to understanding the effects of complex mixtures found in our environment. Our research investigates toxicity in exposed populations, and on human cells and zebrafish using environmental samples, allowing us to identify mechanisms of mixture toxicity and improve health risk assessment of environmental pollution.
Current projects focus on air pollution in urban and rural environments, and past projects have included research on mixture effects associated with contaminated soils (Environ Sci Technol 2015, Environ Res 2020), indoor air quality in preschools (Sci Total Environ 2021), and occupational exposure to pesticides and genotoxicity in Bolivian populations (Sci Total Environ 2019, J Expo Sci Environ Epidemiol 2020). We investigate the effects of genotoxic chemicals and mixtures on transcription and replication fidelity by studying RNA (NAR 2017, PNAS 2018) and DNA mutagenesis.
Current projects
Development of new approach methodologies for assessing cancer risks associated with air pollution mixtures
Current strategies for cancer risk assessment (CRA) of air pollution are today based on a pollutant-by-pollutant approach. This is a great simplification and excludes the possibility of mixture effects that may underestimate actual human health risks. The aim of this project is to address these issues by developing a New Approach Method (NAM) for CRA of air pollution mixtures. We propose that CRA of complex mixtures should be based on in vitro toxicity testing of whole mixtures and determination of relative Mixture Potency Factors (MPFs) (Toxicology 2014). We have previously shown that this approach can accurately determine the genotoxic potency of individual air pollutants (Environ Sci Technol 2017). Using this NAM, we aim to show that CRA of air pollution based on in vitro MPFs better predict the lung cancer risk associated with exposure to ambient air PM than currently accepted component-based approaches. We are now applying this NAM with samples representing different emission sources and environments (Environ Int 2022). This project is funded by the Swedish Research Council FORMAS, STINT/CAPES, and Karolinska Institutet. PI: Kristian Dreij
Mutational signatures of environmental complex mixtures
Experimentally determined mutational signatures have provided important insights into the agents and processes that cause of human cancer. Although humans mainly are exposed to complex mixtures of agents that may contribute to carcinogenesis, this research has focused exclusively on single mutagens. The overall objective of this project is to determine mutational signatures induced by complex environmental mixtures in human cells, thereby improving the understanding of the mechanisms and the role of mixtures versus single agents in cancer etiology. This project is funded by the Swedish Research Council VR and Karolinska Institutet. PI: Kristian Dreij
Assessment of acute respiratory and cardiovascular health effects due to biomass smoke exposure in the Brazilian Amazon
Biomass burning is a global concern in terms of climate change, biodiversity, and health risks. Worldwide, approximately 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 goal is to assess the acute cardiopulmonary health effects of short-term exposure to biomass PM among the population in the 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. This project will be the first of its kind to combine personal exposure monitoring, specific cardiopulmonary biomarkers, and functional testing with mechanistic in vitro studies of collected PM in the Amazon. This project is funded by the Swedish Research Council FORMAS and Karolinska Institutet. PI: Felipe de Oliveira Galvão