Our current research focuses on developing advanced human liver cell models to study chronic liver disease, namely metabolic dysfunction-associated steatotic liver disease (MASLD). These models are designed to improve our understanding of the complex mechanisms underlying disease susceptibility and progression, with a particular focus on chronic inflammation and drug metabolism.
Gaining such insights will facilitate the identification of novel therapeutic targets as well as the discovery of diagnostic and prognostic biomarkers. A key aspect of our work is investigating the role of the cytochrome P450 enzyme complex and its genetic polymorphisms in the onset and progression of this disease.
To achieve this, we employ a diverse range of cutting-edge techniques, including 3D culture methods for the generation of liver spheroids, high-resolution imaging approaches such as confocal microscopy, a comprehensive array of biochemical assays to assess the functional performance of our liver models, as well as genetic engineering approaches to model relevant polymorphisms.
Our group is highly dynamic and operates within an international, interdisciplinary environment, providing an inspiring and collaborative setting for innovative research.
Projects
- Halt RONIN | Dec 2022- Nov 2026 - “Discovering chronic inflammation biomarkers that define key stages in the Healthy-to-NASH (non- alcoholic steatohepatitis) transition to inform early prevention and treatment strategies”
Horizon Europe (HORIZON-HLTH-2022-STAYHLTH-02) Personalized blueprint of chronic inflammation in health-to-disease transition
Publications
- 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
Colaborations
- Prof. Leonard Nelson, Centre for Biomedicine & Global Health, School of Applied Sciences, Edinburgh Napier University, Edinburgh, UK
- Prof. Javier Cubero, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
- Prof. Joana Miranda, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
- Dr. Gilles Truan, Toulouse Biotechnology Institute, Université de Toulouse, Toulouse, France
- Dr. Amit Pandey, Faculty of Medicine, Universität Bern, Bern, Switzerland