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Grey Building | Rua Câmara Pestana 6, 1150-082 Lisbon, Portugal

Michel Kranendonk

Investigador  Investigador Principal
Principal Investigator

Michel Kranendonk is Principal Investigator at NOVA Medical School, Universidade Nova de Lisboa. His research focuses on the mechanistic and functional aspects of drug metabolism, with emphasis on human cytochrome P450 enzymes and their redox partner NADPH-cytochrome P450 oxidoreductase (CPR/POR). He has significantly advanced understanding of the genetic and biochemical determinants of CYP-mediated metabolism, the structure–function basis of P450–reductase interactions, and the development of in vitro models to study drug metabolism, drug-induced liver injury, and chronic liver disease. His work also explores the impact of natural genetic variants on enzyme function and interindividual variability in xenobiotic metabolism.

Dr. Kranendonk leads the Xenobiotic Metabolism Research Group within CHRC at NOVA Medical School and was coordinator of the ToxOmics research center. He served on the Management Committee of the EU COST Action PRO-EURO-DILI-NET and is a member of the Executive Committee of the Horizon Europe project Halt RONIN on chronic liver disease. He also sits on the International Advisory Committee of the Cytochrome P450 Conferences.

He has published extensively on P450 enzymes and CPR, including studies of CYP–CPR interactions, effects of CPR mutations on CYP metabolism, and POR variants linked to Antley-Bixler syndrome. More recently, his group has contributed to consensus efforts on advanced preclinical models for drug-induced liver injury, bridging fundamental enzymology with translational applications in liver disease and drug safety. 

  • Lucena MI, Villanueva-Paz M, Alvarez-Alvarez I, Aithal GP, Björnsson ES, Cakan-Akdogan G, Cubero FJ, Esteves F, Falcon-Perez JM, Fromenty B, Garcia-Ruiz C, Grove JI, Konu O, Kranendonk M, Kullak-Ublick GA, Miranda JP, Remesal-Doblado A, Sancho-Bru P, Nelson L, Andrade RJ, Daly AK, Fernandez-Checa JC, (2024) Roadmap to DILI research in Europe. A proposal from COST action ProEuroDILINet. Pharmacol Res., 200: 107046. doi: 10.1016/j.phrs.2023.107046.
  • Barata IS, Rueff J, Kranendonk M, Esteves F (2024) Pleiotropy of Progesterone Receptor Membrane Component 1 in Modulation of Cytochrome P450 Activity. J Xenobiotics 14, 575-603. doi: 10.3390/jox14020034
  • Esteves F, Rueff J, Kranendonk M. (2021) The Central Role of Cytochrome P450 in Xenobiotic Metabolism-A Brief Review on a Fascinating Enzyme Family. J. Xenobiotics 11, 94-114. DOI: 10.3390/jox11030007
  • Fernandez-Checa JC, Bagnaninchi P, Ye H, Sancho-Bru P, Falcon-Perez JM, Royo F, Garcia-Ruiz C, Konu O, Miranda J, Lunov O, Dejneka A, Elfick A, McDonald A, Sullivan GJ, Aithal GP, Lucena MI, Andrade RJ, Fromenty B, Kranendonk M, Cubero FJ, Nelson LJ (2021) Advanced preclinical models for evaluation of drug-induced liver injury - consensus statement by the European Drug-Induced Liver Injury Network [PRO-EURO-DILI-NET]. J. Hepatology, 24, S0168-8278 (21) 00441-4. DOI: 10.1016/j.jhep.2021.06.021
  • Esteves F, Urban P, Rueff J, Truan G, Kranendonk M. (2020) Interaction Modes of Microsomal Cytochrome P450s with Its Reductase and the Role of Substrate Binding. Int J Mol Sci 21(18): 6669. DOI: 10.3390/ijms21186669
  • Esteves F, Campelo D, Gomes BC, Urban P, Bozonnet S, Lautier T, Rueff J, Truan G, Kranendonk M. (2020) The Role of the FMN-Domain of Human Cytochrome P450 Oxidoreductase in Its Promiscuous Interactions with Structurally Diverse Redox Partners. Front. Pharmacology, 11, 299. eCollection. DOI: 10.3389/fphar.2020.00299
  • Campelo D, Esteves F, Brito Palma B, Costa Gomes B, Rueff J, Lautier T, Urban P, Truan G, Kranendonk M. (2018) Probing the Role of the Hinge Segment of Cytochrome P450 Oxidoreductase in the Interaction with Cytochrome P450. Int J Mol Sci, 19: pii: E3914. DOI: 10.3390/ijms19123914
  • Esteves F, Campelo D, Urban P, Bozonnet S, Lautier T, Rueff J, Truan G, Kranendonk M. (2018) Human cytochrome P450 expression in bacteria: Whole-cell high-throughput activity assay for CYP1A2, 2A6 and 3A4. Biochem Pharmacol, 158:134-140. DOI: 10.1016/j.bcp.2018.10.006
  • Pandey AV, Henderson CJ, Ishii Y, Kranendonk M, Backes WL, Zanger UM (editors) (2018). Role of Protein-Protein Interactions in Metabolism: Genetics, Structure, Function. Front Res Topic ebook in: Front Pharmacology ISBN 978-2-88945-491-4
  • Campelo D, Lautier T, Urban P, Esteves F, Bozonnet S, Truan G, Kranendonk M. (2017) The hinge segment of human NADPH-cytochrome P450 reductase in conformational switching: the critical role of ionic strength. Front Pharmacol 8:755. DOI: 10.3389/fphar.2017.00755

ORCID: 0000-0003-1362-0076
Ciência Vitae: FC1B-515E-3C03