Vous êtes ici : Accueil > Le laboratoire > Thierry Douki

Thierry Douki

Publié le 27 juin 2024
Address
IRIG/SyMMES
CEA-Grenoble
17 avenue des Martyrs
38054 Grenoble Cedex 9
France

Education
1988-1989: Master in organic synthesis (Lyon, France)
1986-1989: Engineering School of Chemistry (Lyon, France)
1983-1985: University School of Technicians in Chemistry (Lyon, France)

Research and professional experience
Since November 1993: senior scientist at the Atomic Energy Commission, CEA-Grenoble; France
current position: deputy-head of the SyMMES laboratory, researcher in the CIBEST team.
1992-1993: Post-doctoral fellowship, Prof. Bruce Ames' laboratory (UC Berkeley, California, USA)
topic: Genotoxic effects of nitric oxide and lipid peroxidation
1989-1992: Thesis in chemistry, supervisor Jean Cadet (CEA Grenoble)
topic: Far-UV photochemistry of DNA models

Scientific Interests
My work in toxicology aims at linking results from test tube experiments with those of cellular studies. Analytical chemistry, in particular HPLC coupled to tandem mass spectrometry, is very powerful for this purpose. I could thus gather large amounts of information on the induction of DNA damage. More recently, I applied this method to the quantification of specific molecular biomarkers of exposure in biological fluids.

     Photobiology.
A large fraction of my activity deals with the formation of UV-induced photodamage in DNA. A main breakthrough was the development in the early 2000’s of a HPLC-mass spectrometry-based assay for the individual quantification of all possible photoproducts. This made possible the collection of novel data on the photochemistry of double-stranded DNA as well as major applications in mammalian cells. In particular, we established that the UVA range of sunlight generates some of the photoproducts believed to be due only to UVB. We also gathered new information on DNA repair and worked with the cosmetics industry on photoprotection. We recently provide evidence for an impact of blue light on repair.
    ​Recent publications on the topic:
Douki, T. (2020) Pyrimidine (6‐4) pyrimidone photoproducts in UVA‐irradiated DNA: photosensitization or photoisomerization? ChemPhotoChem 4, 294-299. https://doi.org/10.1002/cptc.201900280
Josse, G., Gravier, E. and Douki, T. (2020) Method for the accurate determination of the DNA protection factor of sun protection products. Brit. J. Dermatol. 183, 178-179. 10.1111/bjd.18936
Douki, T. (2020) Oxidative stress and genotoxicity in melanoma induction: impact on repair rather than formation of DNA damage? Photochem. Photobiol. 96, 962-972. 10.1111/php.13278
Fajuyigbe, D., Douki, T., van Dijk, A., Sarkany, R. P. E. and Young, A. R. (2021) Dark cyclobutane pyrimidine dimers are formed in the epidermis of Fitzpatrick skin types I/II and VI in vivo after exposure to solar simulated radiation. Pigment Cell Melanoma Res. 34, 575–584. 10.1111/pcmr.12956
Reynaud, N., Belz, L., Beal, D., Bacqueville, D., Duplan, H., Genies, C., Questel, E., Josse, G. and Douki, T. (2022) DNA photoproducts released by repair in biological fluids as biomarkers of the genotoxicity of UV radiation. Anal. Bioanal. Chem. 414, 7705-7720. 10.1007/s00216-022-04302-1
Douki, T., Bacqueville, D., Jacques, C., Genies, C., Roullet, N., Bessou-Touya, S. and Duplan, H. (2024) Blue light impairs the repair of UVB-induced pyrimidine dimers in a human skin model. Photochem Photobiol. 10.1111/php.13921

     Formation of adducts by covalent binding of organic compounds to DNA.
I am interested the genotoxicity of polycyclic aromatic hydrocarbons and the formation of DNA adducts. A particular focus is the identification of factors that modulates metabolism and genotoxicity of these compounds like mixture effects and co-exposure with sunlight. More recently, I studied the deleterious effects of exposure to sulfur mustard. This project is performed in collaboration with CEA-Saclay and the French Army Biomedical Research Institute. We developed assays for the quantification glutathione derivatives used biomarkers, which can be detected in culture media, plasma and urine. Data have been obtained in animals either cutaneously or ocularly exposed.
    Recent publications on the topic:
von Koschembahr, A., Youssef, A., Beal, D., Bourgart, E., Rivier, A., Marques, M., Leccia, M. T., Giot, J. P., Maitre, A. and Douki, T. (2020) Metabolism and genotoxicity of polycyclic aromatic hydrocarbons in human skin explants: mixture effects and modulation by sunlight. Arch. Toxicol. 94, 495–507. 10.1007/s00204-019-02650-z
von Koschembahr, A., Youssef, A., Beal, D., Gudimard, L., Giot, J. P. and Douki, T. (2020) Toxicity and DNA repair in normal human keratinocytes co-exposed to benzo[a]pyrene and sunlight. Toxicol. Vitro 63, 104744. 10.1016/j.tiv.2019.104744
Gilardoni, M., Leonco, D., Caffin, F., Gros-Desormeaux, F., Eldin, C., Beal, D., Ouzia, S., Junot, C., Fenaille, F., Pierard, C. and Douki, T. (2021) Evidence for the systemic diffusion of (2-chloroethyl)-ethyl-sulfide, a sulfur mustard analog, and its deleterious effects in brain. Toxicology 462, 152950. 10.1016/j.tox.2021.152950
Roser, M., Beal, D., Eldin, C., Gudimard, L., Caffin, F., Gros-Desormeaux, F., Leonco, D., Fenaille, F., Junot, C., Pierard, C. and Douki, T. (2021) Glutathione conjugates of the mercapturic acid pathway and guanine adduct as biomarkers of exposure to CEES, a sulfur mustard analog. Anal. Bioanal. Chem. 413, 1337–1351. 10.1007/s00216-020-03096-4
Bouhlel, J., Caffin, F., Gros-Désormeaux, F., Douki, T., Benoist, J.-F., Castelli, F., Chu-Van, E., Piérard, C., Junot, C. and Fenaille, F. (2024) Metabolomics Analysis of Rabbit Plasma after Ocular Exposure to Vapors of Sulfur Mustard. Metabolites 14, 349. 10.3390/metabo14070349

     Non-additive effect.
A major topic in toxicology is the effect of complex exposures and the notion of exposome. It is thus important to develop tools for the assessment of the risk associated with exposure to complex mixtures. I am working on methods of data processing that would either help identifying situations of non-additivity (combination index) and predicting effects of various mixtures (experimental design). Results have been obtained with combinations of different ranges of UV radiation and work is ongoing with organic pollutants.
    Recent publications on the topic:
Douki, T. (2021) Wavelengths and temporal effects on the response of mammalian cells to UV radiation: Limitations of action spectra illustrated by genotoxicity. J Photochem Photobiol B 217, 112169. 10.1016/j.jphotobiol.2021.112169
Douki, T. and Buhot, A. (2022) Synergistic or Antagonist Effects of Different UV Ranges Analyzed by the Combination Index: Application to DNA Photoproducts. Photochem. Photobiol. 98, 649-661. 10.1111/php.13528
Douki, T., Millot, O. and Buhot, A. (2024) Data processing for predicting DNA damaging properties of complex UV sources. Chemphyschem in press. 10.1002/cphc.202400549

Scientific production
220 original research articles, 40 review articles and 30 book chapters (WoS H-index: 72.

Awards
2018: Research Award of the American Society for Photobiology
2016: Photon Award for the most cited review in the journal of the American Society for Photobiology
2006: New investigator Award of the American Society for Photobiology
1995: Young Scientist Award of the French Society for Photobiology

Scientific activities
Expert for ANSES (French Agency for Food, Environmental and Occupational Health & Safety)
Member of the American, European and French (President) Societies for Photobiology
Member of the French Society for Genetic Toxicology
Associate editor for Photochemistry and Photobiology
President of the organizing committee of the 20th Meeting of the European Society for Photobiology (2023, Lyon, France)

Link to the complete list of publications. ​