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Kristian Dreij

Kristian Dreij

Senior researcher

Affiliations:
Biochemical toxicology
Departments:
Institute of Environmental Medicine (IMM), C6

About me

Kristian Dreij was born 1976 in Nässjö, Sweden. He received his M.Sc. degree in Toxicology in 2000 and a Ph.D. degree in Toxicology in 2005 from Professor Bengt Jernström’s group, Karolinska Institutet (KI), Stockholm, Sweden. 2006 he joined Professor David Scicchitano’s group for a postdoc in molecular biology at New York University, New York, USA. In 2009 he was recruited to the group of Professor Ulla Stenius, KI as a post-doctoral fellow focusing on genetic toxicology. 2012 he was awarded a Junior Researcher project grant from the Swedish Research Council VR to start a group focused on the biological effects of transcriptional mutagenesis at the Institute of Environmental Medicine, KI. In addition, his group is investigating if mixture effects can contribute to the genotoxic and carcinogenic effects of environmental pollutants such as PAHs and pesticides, and how this should be included in risk assessment. A more detailed description of the ongoing research is found below. Kristian became Docent/Associate Professor at Karolinska Institutet in 2016.

Kristian is also the program study director of the global master's programme in toxicology at Karolinska Institutet.

Research description

There are two main projects in the lab. (1) Biological consequences of transcriptional errors, and (2) Mixtures effects of environmental pollutants.

 

1. Biological consequences of transcriptional errors induced by DNA damage.

When a DNA-damage is bypassed during transcription this can lead to RNA misincorporation, a process termed transcriptional mutagenesis (TM). Although the concept of TM is well known, the biological consequences are still a recent discovery. While the few existing studies of TM have begun to shed light on the process, many issues have yet to be addressed. The extent, to which TM occurs in mammalian cells and the role these seemingly transient errors might play in disease processes such as carcinogenesis, is currently unknown. Current theories postulate that the transient expression of mutant proteins via TM could play a major role in tumor development by stimulating proliferation of a senescent initiated, precancerous cell or allowing it to escape growth-inhibitory apoptotic signals and undergo clonal expansion. In order to characterize each of these events, a  unique approach has been developed for studying the occurrence and potentially detrimental effects originating from TM.

For more details: Transcriptional mutagenesis and cellular effects

Selected publications

O6-methylguanine-induced transcriptional mutagenesis reduces p53 tumor-suppressor function. Ezerskyte M, Paredes JA, Malvezzi S, Burns JA, Margison GP, Olsson M, Scicchitano DA, Dreij K. Proc Natl Acad Sci U S A. 2018 May 1;115(18):4731-4736.

Transcriptional mutagenesis reduces splicing fidelity in mammalian cells. Paredes JA, Ezerskyte M, Bottai M, Dreij K. Nucleic Acids Res. 2017 Jun 20;45(11):6520-6529

 

2. Contribution of interaction effects to the carcinogenicity of environmental pollutants.

The goal of this project is to investigate the harmful effects of exposure to complex mixtures of PAHs and pesticides, and to improve the scientific base for risk assessment of human exposure to complex environmental mixtures. The methods commonly used for assessing the toxicity of complex environmental mixtures probably significantly underestimate the risk of exposure to human health since they do not take into account interactions which potentially give rise to synergistic effects.

In the PAH project we study the effects of complex mixtures using environmental samples on DNA damage and repair, inflammation and development. Samples are obtained from urban air particulate matter and soil collected at urban as well as industrial locations. The test systems we use are human cell lines and zebrafish embryos. Our published data indicate that complex environmental PAH mixtures induce unexpected and persistent DNA damage.

In the pesticide project we are conducting a cross-sectional study among the Bolivian agricultural population. In Bolivia, farmers have increased the use of pesticides to enter into a more competitive international market. There is little or no social protection which together leads to hazardous working conditions for the farmers. To evaluate and study the correlation between exposure to pesticides and risk of developing genotoxic effects we use questionnaire information and blood and urine analysis. 

For more details:

Selected publications

Pesticide exposure among Bolivian farmers: associations between worker protection and exposure biomarkers. Barrón Cuenca J, Tirado N, Vikström M, Lindh CH, Stenius U, Leander K, Berglund M, Dreij K. J Expo Sci Environ Epidemiol. 2019 Feb 20.

Cancer Risk Assessment of Airborne PAHs Based on in Vitro Mixture Potency Factors. Dreij K, Mattsson Å, Jarvis IWH, Lim H, Hurkmans J, Gustafsson J, Bergvall C, Westerholm R, Johansson C, Stenius U. Environ Sci Technol. 2017 Aug 1;51(15):8805-8814. 

 

Funding

  • Cancer och Allergi-fonden
  • Carl Tryggers Stiftelse
  • Institute of Environmental Medicine
  • Seventh Framework Program Marie Curie International Reintegration Grant (IRG)
  • Stockholm County Council
  • Stockholm City Department of Environment
  • Swedish International Development Cooperation Agency (SIDA)
  • Swedish Research Council (VR)
  • ÅForsk

 

Research group

 

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