Emma Wincent is a senior researcher in Molecular Toxicology at Karolinska Institutet, Institute of Environmental Medicine, Unit of Systems Toxicology.
She received her M.Sc. degree in Toxicology in 2002 at Karolinska Institutet (KI) and a Ph.D. degree in Toxicology in 2009 at Stockholm University. In 2009 she joined Professor Agneta Rannug´s group for a postdoc in environmental medicine at KI and was in 2015 recruited to the Swedish Toxicology Sciences Research Center (SWETOX) to lead the research spoke in Toxicokinetics. She returned to KI, to the Institute of Environmental Medicine, in 2018/2019, continuing her research in toxicokinetics and molecular toxicology related areas.
Emma is also course leader and frequent teacher at the global Master's Programme in Toxicology at Karolinska Institutet.
The overall aim of the research in my group is to increase the understanding of how chemical factors may cause toxicity by altering critical biological pathways, and in contrast, how biological factors, such as inflammation, tissue damage or dysbiosis, may influence the outcome of chemical exposure. We are specifically focusing on biotransformation systems and how interactions between chemical/biological factors affecting these may impact immune function, metabolic signaling and cell differentiation.
To study these pathways and functions we use a wide range of experimental models, including recombinant enzymes, tissue fractions, cell cultures and zebrafish, and methods such as toxicity assays, enzyme kinetics, transcriptomics, metabolomics and chromatography (HPLC, LC-MS, GC-MS).
The major ongoing projects are briefly described below.
Project 1: The role of AHR/CYP1-feedback signalling in intestinal barrier homeostasis
The aryl hydrocarbon receptor (AHR), also known as the dioxin receptor, is renowned in toxicology for mediating the adverse effects of environmental pollutants such as dioxins and dioxin-like PCBs. These adverse effects include for example immunotoxicity, reproductive toxicity, endocrine disruption, and carcinogenesis. While the toxicity of AHR signalling has been the focus for the last 40 years within the AHR-field, the focus is more and more shifting to understanding the physiological functions of this receptor pathway, and how these are regulated.
We previously reported on a critical role of the CYP1 enzyme family in regulating AHR signalling during zebrafish embryo development, intestinal immunity in mice and immune cell differentiation. The aim of this project is to investigate how the dichotomy of detrimental vs. beneficial functions of the AHR in might be resolved, focusing on AHR functions in intestinal stem cell differentiation by analysing related endpoints in cells, tissues, or serum from mice models with genetic alterations in the AHR or CYP1 pathways. In addition to stem cell differentiation, we are also investigating effects on metabolic and endocrine signalling. The project is funded by the Swedish Research Council (VR) and performed in collaboration with the research group led by Brigitta Stockinger at the Francis Crick Institute.
Project 2: Chemical impact on tissue repair and regeneration
The purpose of this project is to investigate the impact of xenobiotic chemicals on the ability to repair tissue damage, focusing on the role of the aryl hydrocarbon receptor (AHR) as mediator of key events of tissue repair. While the AHR is a transcription factor originally discovered for mediating the toxicity of xenobiotics, the discovery of natural ligands formed endogenously, present in the diet or formed by commensal microbiota has pinpointed important functions of the AHR in e.g. barrier organs such as the skin, lung, and gut.
Successful tissue repair depends on synchronized and tightly controlled action of the immune system and proliferation/differentiation of tissue-specific stem cells at the site of injury, processes in which physiological AHR signalling has proven to be critical. The aim of this project is to determine if and how xenobiotic chemicals may interfere with tissue repair processes by subverting AHR from its physiological functions, and to determine the consequences of such interference. This is achieved using zebrafish models for tissue repair and regeneration, and by combining OMICS-based effect screening with targeted analysis of markers for tissue integrity and inflammatory signalling.
The project is financed by the Swedish Research Council Sustainable Development (FORMAS).
Project 3: Toxicokinetic modelling of internal dose in zebrafish (Danio rerio) embryo
The zebrafish embryo is increasingly used as a vertebrate animal model to assess adverse effects of chemicals. The acceptance of such tests from a health risk assessment perspective relies on the possibility to extrapolate toxicity data from zebrafish embryo tests to humans, similar to the extrapolations from laboratory animals such as mice and rats carried out today. Until now, little attention has been paid to the relation between external and internal dose in fish embryos. Detailed knowledge of the toxicokinetic processes including adsorption, distribution, and the resulting target dose, and physiologically based toxicokinetic (PBTK) models are frequently used to characterize the internal dose and to extrapolate animal toxicity data to humans.
The aim of this project is to develop a better understanding of the toxicokinetics and target dose of chemical substances in the zebrafish embryo by a combination of experimental toxicokinetic studies, mathematical modelling, and Mass Spectrometry Imaging techniques. This project is performed in collaboration with Carolina Vogs at the Swedish University of Agricultural Sciences and the research group led by Per Andrén at Uppsala University.
See also descriptions of projects performed by members of the Wincent research group:
- Dennis Lindqvist
- Carolina Vogs
- Ingrid Medina
- Rodrigo Disner
Kinetics and toxicity of an environmentally relevant mixture of halogenated organic compounds in zebrafish embryo. Lindqvist D, Wincent E. Aquatic Toxicology. 2022 Nov.
AHR in the intestinal microenvironment: safeguarding barrier function. Stockinger B, Shah K, Wincent E. Nature Reviews Gastroenterol Hepatol. 2021 Mar 19.
Toxicokinetics of Perfluorinated Alkyl Acids Influences Their Toxic Potency in the Zebrafish Embryo (Danio rerio). Vogs C, Johansson G, Näslund M, Wulff S, Sjödin M, Hellstrandh M, Lindberg J, Wincent E. Environ Sci Technol. 2019 Apr 2;53(7):3898-3907.
Cytochrome P4501-inhibiting chemicals amplify aryl hydrocarbon receptor activation and IL-22 production in T helper 17 cells. Schiering C, Vonk A, Das S, Stockinger B, Wincent E. Biochem Pharmacol. 2018 May;151:47-58.
Feedback control of AHR signalling regulates intestinal immunity. Schiering C, Wincent E, Metidji A, Iseppon A, Li Y, Potocnik AJ, Omenetti S, Henderson CJ, Wolf CR, Nebert DW, Stockinger B. Nature. 2017 Feb 9;542(7640):242-245.
Biological effects of 6-formylindolo[3,2-b]carbazole (FICZ) in vivo are enhanced by loss of CYP1A function in an Ahr2-dependent manner. Wincent E, Kubota A, Timme-Laragy A, Jönsson ME, Hahn ME, Stegeman JJ. Biochem Pharmacol. 2016 Jun 15;110-111:117-29
Induction and inhibition of human cytochrome P4501 by oxygenated polycyclic aromatic hydrocarbons. Wincent E, Le Bihanic F, Dreij K. Toxicol. Res. 2016 Mar 5:788-99
Evidence for new light-independent pathways for generation of the endogenous aryl hydrocarbon receptor agonist FICZ. Smirnova A, Wincent E, Vikström Bergander L, Alsberg T, Bergman J, Rannug A, Rannug U. Chem Res Toxicol. 2016 Jan 19;29(1):75-86.
Combination effects of AHR agonists and Wnt/β-catenin modulators in zebrafish embryos: Implications for physiological and toxicological AHR functions. Wincent E, Stegeman JJ, Jönsson ME. Toxicol Appl Pharmacol. 2015 Apr 15;284(2):163-79
Quercetin, resveratrol, and curcumin are indirect activators of the aryl hydrocarbon receptor (AHR). Mohammadi Bardbori A, Bengtsson J, Rannug U, Rannug A, Wincent E. Chem Res Toxicol. 2012 Sep 17;25(9):1878-84.
Inhibition of cytochrome P4501 as a novel mechanism of Ah receptor activation. Wincent E, Bengtsson J, Mohammadi Bardbori A, Alsberg T, Luecke S, Rannug U, Rannug A. Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):4479-84.
Cytochrome P450 1A1 gene regulation by UVB involves crosstalk between the aryl hydrocarbon receptor and nuclear factor kappa B. Luecke S, Wincent E, Backlund M. Rannug U, Rannug A. Chem. Biol. Interact. 2010 Mar 30;184(3):466-73.
- Course leader at the Global Master Program in Toxicology at Karolinska instututet: Target Organ Toxicology - Toxicokinetics and Toxicodynamics.
- Teacher in toxicology-related topics: Receptor signalling; Biotransformation; Gebetic Toxicology; Endocrine Disruption