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Molecular and Computational Toxicology

The Division of Molecular and Computational Toxicology is specialised in developing computational and human in vitro (non-animal) based strategies for the understanding of the molecular mechanisms of chemical-induced toxicity in order to better predict chemical safety in humans.

The research combines and integrates three main tracks:

  1. Phase I and phase II metabolism and transport (phase III), including the influences of polymorphisms;
  2. Molecular mechanisms of chemical- and nanomaterial-  induced cellular perturbations (primarily kidney and liver cells);
  3. Computational methods for site of metabolism prediction including molecular docking and dynamics.

The laboratory is specialised in analytical chemistry, cell culture, toxicity determination, omic analysis, molecular docking and dynamics. In vitro models include human primary cells, human cell lines and induced human Pluripotent Stem Cell derived cells.

Lecture

Cormac Murphy from the group Molecular and Computational Toxicology, Dept of Chemistry and Pharmaceutical Sciences giving an inspiring talk on Organs on Chip to Masters Students of the track Drug Discovery and Safety.

Interested in more? Click here to see a Guest Lecture on Human in vitro models and assays for nephrotoxicity prediction.

Publications

  • Publications

    All Publications [ Link ]

    Recent publications

    2021: Generation and characterization of iPSC-derived renal proximal tubule-like cells with extended stability.  Chandrasekaran V, Carta G, da Costa Pereira D, Gupta R, Murphy C, Feifel E, Kern G, Lechner J, Cavallo AL, Gupta S, Caiment F, Kleinjans JCS, Gstraunthaler G, Jennings P, and Wilmes A.  Journal https://pubmed.ncbi.nlm.nih.gov/34078926/  10.1038/s41598-021-89550-4

    2020: Multiparametric assessment of mitochondrial respiratory inhibition in HepG2 and RPTEC/TERT1 cells using a panel of mitochondrial targeting agrochemicals. W. van der Stel, G. Carta, J. Eakins, S. Darici, J. Delp, A. Forsby, S. H. Bennekou, I. Gardner, M. Leist, E. H. J. Danen, P. Walker, B. van de Water, and P. Jennings. Journal https://www.ncbi.nlm.nih.gov/pubmed/32607615  10.1007/s00204-020-02792-5

    2020: New approach methodologies (NAMs) for human-relevant biokinetics predictions: Meeting the paradigm shift in toxicology towards an animal-free chemical risk assessment. A. Punt, H. Bouwmeester, B. J. Blaauboer, S. Coecke, B. Hakkert, D. F. G. Hendriks, P. Jennings, N. I. Kramer, S. Neuhoff, R. Masereeuw, A. Paini, Aacm Peijnenburg, M. Rooseboom, M. L. Shuler, I. Sorrell, B. Spee, M. Strikwold, A. D. Van der Meer, M. Van der Zande, M. Vinken, H. Yang, P. M. J. Bos, and M. B. Heringa. Journal https://www.ncbi.nlm.nih.gov/pubmed/32521035  10.14573/altex.2003242

    2020: Acetylene containing cyclo(L-Tyr-L-Tyr)-analogs as mechanism-based inhibitors of CYP121A1 from Mycobacterium tuberculosis. S. Ortega Ugalde, K. Wallraven, A. Speer, W. Bitter, T. N. Grossmann, and J. N. M. Commandeur. Journal 177, 113938 https://www.ncbi.nlm.nih.gov/pubmed/32224137  10.1016/j.bcp.2020.113938

    2020: Combined Linear Interaction Energy and Alchemical Solvation Free-Energy Approach for Protein-Binding Affinity Computation. E. A. Rifai, V. Ferrario, J. Pleiss, and D. P. Geerke. Journal 16, 1300-1310 https://www.ncbi.nlm.nih.gov/pubmed/31894691  10.1021/acs.jctc.9b00890

    2020: Vision of a near future: Bridging the human health-environment divide. Toward an integrated strategy to understand mechanisms across species for chemical safety assessment. C. Rivetti, T. E. H. Allen, J. B. Brown, E. Butler, P. L. Carmichael, J. K. Colbourne, M. Dent, F. Falciani, L. Gunnarsson, S. Gutsell, J. A. Harrill, G. Hodges, P. Jennings, R. Judson, A. Kienzler, L. Margiotta-Casaluci, I. Muller, S. F. Owen, C. Rendal, P. J. Russell, S. Scott, F. Sewell, I. Shah, I. Sorrel, M. R. Viant, C. Westmoreland, A. White, and B. Campos. Journal 62, 104692 https://www.ncbi.nlm.nih.gov/pubmed/31669395  10.1016/j.tiv.2019.104692

    2020: Polarisable force fields: what do they add in biomolecular simulations? V. S. Inakollu, D. P. Geerke, C. N. Rowley, and H. Yu. Journal 61, 182-190 https://www.ncbi.nlm.nih.gov/pubmed/32044671  10.1016/j.sbi.2019.12.012

Research

  • Projects

    The group is a partner in several EU level projects on drug and chemical safety, including EUToxRisk, OpenRiskNet and the completed IMI projects StemBANCC and MIP-DILI. Anja has a new project on matrigel replacement, funded by Stiftung zur Foerderderung der Erforschung von Ersatz- und Ergänzungsmethoden zur Einschränkung von Tierversuchen (set). Read more here.

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