Beating Goliath: Generation Of NoveL, Integrated and Internationally Harmonised Approaches for Testing Metabolism Disrupting Compounds

Deliverables

Detailed review paper on state of the art on MDCs

A detailed review will be performed of the existing literature, databases and reports from ongoing sister projects in order to synthesize the available information on relevant exposures, molecular mechanisms and adverse health effects associated with exposure to MDCs. This will include a review of published information on in vitro and animal studies, as well as human epidemiological data on measured metabolic endpoints and biomarkers and association with exposure (UU). We will use where appropriate information available from HBM4EU, EUROMIX, and others. In HBM4EU, beneficiaries UU and VITO are involved in systematically evaluating and categorizing effect biomarkers for different health endpoints including metabolic disorders. This review will allow the prioritization of molecular initiating events (MIE), key effects and biological endpoints associated with metabolic disorders, and will provide an information base for the selection of MoA and biomarkers for subsequent analysis in WP1-5.

Website open to the general public

Website will be launched which includes pertinent information about the GOLIATH project including objectives background consortium links to other projects and news and updates It will be userfriendly and have an attractive design

Publications

2,4-Di-tert-butylphenol Induces Adipogenesis in Human Mesenchymal Stem Cells by Activating Retinoid X Receptors

Author(s): Xiao-Min Ren, Richard C Chang, Yikai Huang, Angélica Amorim Amato, Coralie Carivenc, Marina Grimaldi, Yun Kuo, Patrick Balaguer, William Bourguet, Bruce Blumberg
Published in: Endocrinology, 2023, ISSN 0013-7227
Publisher: The Endocrine Society
DOI: 10.1210/endocr/bqad021

Systematic analysis of chemical-protein interactions from zebrafish embryo by proteome-wide thermal shift assay, bridging the gap between molecular interactions and toxicity pathways.

Author(s): Veronica Lizano-Fallas; Ana Maria Carrasco Del Amor; Susana Cristobal
Published in: Journal of Proteomics, Issue 1, 2021, ISSN 1874-3919
Publisher: Elsevier BV
DOI: 10.1016/j.jprot.2021.104382

Prediction of Molecular Initiating Events for Adverse Outcome Pathways Using High-Throughput Identification of Chemical Targets

Author(s): Veronica Lizano-Fallas, Ana Carrasco del Amor, Susana Cristobal
Published in: Toxics, 2023, ISSN 2305-6304
Publisher: MDPI
DOI: 10.3390/toxics11020189

Candidate Proficiency Test Chemicals to Address Industrial Chemical Applicability Domains for in vitro Human Cytochrome P450 Enzyme Induction

Author(s): Miriam Naomi Jacobs, Barbara Kubickova, Eugene Boshoff
Published in: Frontiers in Toxicology, 2022, ISSN 2673-3080
Publisher: Frontiers
DOI: 10.3389/ftox.2022.880818

Role of Mitochondrial Cytochrome P450 2E1 in Healthy and Diseased Liver.

Author(s): Julie Massart; Karima Begriche; Jessica H. Hartman; Bernard Fromenty
Published in: Cells, 2021, ISSN 2073-4409
Publisher: MDPI
DOI: 10.3390/cells11020288

Reproducibility of adipogenic responses to metabolism disrupting chemicals in the 3T3-L1 pre-adipocyte model system: An interlaboratory study

Author(s): Christopher D. Kassotis, Kate Hoffman, Johannes Völker, Yong Pu, Almudena Veiga-Lopez, Stephanie M. Kim, Jennifer J. Schlezinger, Patrizia Bovolin, Erika Cottone, Astrid Saraceni, Rosaria Scandiffio, Ella Atlas, Karen Leingartner, Stacey Krager, Shelley A. Tischkau, Sibylle Ermler, Juliette Legler, Vesna A. Chappell, Suzanne E. Fenton, Fahmi Mesmar, Maria Bondesson, Mariana F. Fernández, Heather
Published in: Toxicology, 2021, ISSN 0300-483X
Publisher: Elsevier BV
DOI: 10.1016/j.tox.2021.152900

Mechanistic insights into the synergistic activation of the RXR–PXR heterodimer by endocrine disruptor mixtures

Author(s): Vanessa Delfosse, Tiphaine Huet, Deborah Harrus, Meritxell Granell, Maxime Bourguet, Caroline Gardia-Parège, Barbara Chiavarina, Marina Grimaldi, Sébastien Le Mével, Pauline Blanc, David Huang, Jakub Gruszczyk, Barbara Demeneix, Sarah Cianférani, Jean-Baptiste Fini, Patrick Balaguer, William Bourguet
Published in: Proceedings of the National Academy of Sciences, 2021, ISSN 0027-8424
Publisher: National Academy of Sciences
DOI: 10.1073/pnas.2020551118

G protein-coupled estrogen receptor activation by bisphenol-A disrupts the protection from apoptosis conferred by the estrogen receptors ERα and ERβ in pancreatic beta cells.

Author(s): Ignacio Babiloni-Chust; Reinaldo S. dos Santos; Regla M. Medina-Gali; Atenea A. Perez-Serna; José-Antonio Encinar; Juan Martinez-Pinna; Jan-Ake Gustafsson; Laura Marroqui; Angel Nadal
Published in: reponame:RUA. Repositorio Institucional de la Universidad de Alicante, 2022, ISSN 0160-4120
Publisher: Pergamon Press Ltd.
DOI: 10.1016/j.envint.2022.107250

Nonionic Surfactants can Modify the Thermal Stability of Globular and Membrane Proteins Interfering with the Thermal Proteome Profiling Principles to Identify Protein Targets

Author(s): Emmanuel Berlin; Veronica Lizano-Fallas; Ana Carrasco del Amor; Olatz Fresnedo; Susana Cristobal
Published in: Crossref, 2022, ISSN 0003-2700
Publisher: American Chemical Society
DOI: 10.1021/acs.analchem.2c04500

In Vitro Assays to Identify Metabolism-Disrupting Chemicals with Diabetogenic Activity in a Human Pancreatic β-Cell Model

Author(s): Reinaldo Sousa Dos Santos, Regla María Medina-Gali, Ignacio Babiloni-Chust, Laura Marroqui, Angel Nadal
Published in: Internation Journal for Molecular Sciences, 2022, ISSN 1661-6596
Publisher: MDPI
DOI: 10.3390/ijms23095040

Exposure to a Mixture of Endocrine-Disrupting Chemicals and Metabolic Outcomes in Belgian Adolescents

Author(s): Anran Cai, Sylvie Remy, Virissa Lenters, Bianca Cox, Greet Schoeters, Adrian Covaci, Roel Vermeulen, Lützen Portengen
Published in: Environmental Science & Technology, 2023, ISSN 0013-936X
Publisher: American Chemical Society
DOI: 10.1021/acs.est.3c07607

Screening of Metabolism-Disrupting Chemicals on Pancreatic α-Cells Using In Vitro Methods.

Author(s): Angel Nadal; Ignacio Babiloni Chust; Reinaldo S. Dos Santos; Laura Marroqui Esclapez
Published in: International Journal of Molecular Sciences, 2023, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms24010231

Environmental chemicals change extracellular lipidome of mature human white adipocytes

Author(s): Paula Burkhardt, Susana Alejandra Palma-Duran, Astrud R.R. Tuck, Kalle Norgren, Xinyi Li, Violetta Nikiforova, Julian L. Griffin, Vesna Munic Kos
Published in: Chemosphere, 2024, ISSN 0045-6535
Publisher: Pergamon Press Ltd.
DOI: 10.1016/j.chemosphere.2023.140852

FORUM: building a Knowledge Graph from public databases and scientific literature to extract associations between chemicals and diseases

Author(s): Maxime Delmas; Olivier Filangi; Nils Paulhe; Florence Vinson; Christophe Duperier; William Garrier; Paul-Emeric Saunier; Yoann Pitarch; Fabien Jourdan; Franck Giacomoni; Clément Frainay
Published in: "Bioinformatics, Oxford University Press (OUP), 2021, ⟨10.1093/bioinformatics/btab627⟩", Issue 1, 2020, ISSN 1367-4803
Publisher: Oxford University Press
DOI: 10.1093/bioinformatics/btab627

Endocrine disruptors in plastics alter β-cell physiology and increase the risk of diabetes mellitus

Author(s): Juan Martínez-Pinna; Roberto Sempere-Navarro; Regla M. Medina-Gali; Esther Fuentes; Ivan Quesada; Robert M. Sargis; Leonardo Trasande; Angel Nadal
Published in: Crossref, Issue 2, 2022, ISSN 0193-1849
Publisher: American Physiological Society
DOI: 10.1152/ajpendo.00068.2023

Xenobiotic-Induced Aggravation of Metabolic-Associated Fatty Liver Disease

Author(s): Julie Massart; Karima Begriche; Anne Corlu; Bernard Fromenty
Published in: International Journal of Molecular Sciences, Issue 1, 2022, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms23031062

DEXOM: Diversity-based enumeration of optimal context-specific metabolic networks

Author(s): Pablo Rodríguez-Mier,Nathalie Poupin,Carlo de Blasio,Laurent Le Cam,Fabien Jourdan
Published in: PLOS Computational Biology, 2022, ISSN 1553-7358
Publisher: PLOS
DOI: 10.1371/journal.pcbi.1008730

Agrochemicals and obesity

Author(s): Xiao-Min Ren, Yun Kuo, Bruce Blumberg
Published in: Molecular and Cellular Endocrinology, Issue 515, 2020, Page(s) 110926, ISSN 0303-7207
Publisher: Elsevier BV
DOI: 10.1016/j.mce.2020.110926

Prenatal exposure to persistent organic pollutants and changes in infant growth and childhood growth trajectories

Author(s): Anran Cai, Lützen Portengen, Eva Govarts, Laura Rodriguez Martin, Greet Schoeters, Juliette Legler, Roel Vermeulen, Virissa Lenters, Sylvie Remy
Published in: Chemosphere, 2023, ISSN 0045-6535
Publisher: Pergamon Press Ltd.
DOI: 10.1016/j.chemosphere.2022.137695

ELIXIR and Toxicology: a community in development

Author(s): Marvin Martens; Rob Stierum; Emma L. Schymanski; Chris T. Evelo; Reza Aalizadeh; Hristo Aladjov; Kasia Arturi; Karine Audouze; Pavel Babica; Karel Berka; Jos Bessems; Ludek Blaha; Evan E Bolton; Montserrat Cases; Dimitrios Damalas; Kirtan Dave; Marco Dilger; Thomas Exner; Daan P. Geerke; Roland C. Grafström; Alasdair J. G. Gray; John M. Hancock; Henner Hollert; Nina Jeliazkova; Danyel Jennen; Fab
Published in: F1000 Research, Issue 1, 2022, ISSN 2046-1402
Publisher: F1000 Research Ltd.
DOI: 10.12688/f1000research.74502.1

Development of a reference and proficiency chemical list for human steatosis endpoints in vitro

Author(s): Barbara Kubickova, Miriam N. Jacobs*
Published in: Frontiers in Endocrinology, 2023, ISSN 1664-2392
Publisher: Frontiers
DOI: 10.3389/fendo.2023.1126880

Emerging concepts and opportunities for endocrine disruptor screening of the non-EATS modalities

Author(s): Christopher J.Martyniuk, RubénMartínez, LaiaNavarro-Martín, Jorke H.Kamstra, AdamSchwendt, StéphaneReynaud, LorraineChalifourd
Published in: Environmental Research, 2021, ISSN 0013-9351
Publisher: Academic Press
DOI: 10.1016/j.envres.2021.111904

Towards accurate high-throughput ligand affinity prediction by exploiting structural ensembles, docking metrics and ligand similarity

Author(s): Melanie Schneider, Jean-Luc Pons, William Bourguet, Gilles Labesse
Published in: Bioinformatics, Issue 36/1, 2019, Page(s) 160-168, ISSN 1367-4803
Publisher: Oxford University Press
DOI: 10.1093/bioinformatics/btz538

In Silico Predictions of Endocrine Disruptors Properties

Author(s): Melanie Schneider, Jean-Luc Pons, Gilles Labesse, William Bourguet
Published in: Endocrinology, Issue 160/11, 2019, Page(s) 2709-2716, ISSN 1945-7170
Publisher: Oxford academic
DOI: 10.1210/en.2019-00382

Inhibition of methyltransferase activity of enhancer of zeste 2 leads to enhanced lipid accumulation and altered chromatin status in zebrafish

Author(s): Marjo J. den Broeder, Jarle Ballangby, Leonie M. Kamminga, Peter Aleström, Juliette Legler, Leif C. Lindeman, Jorke H. Kamstra
Published in: Epigenetics & Chromatin, Issue 13/1, 2020, ISSN 1756-8935
Publisher: BioMed Central
DOI: 10.1186/s13072-020-0329-y

The GOLIATH Project: Towards an Internationally Harmonised Approach for Testing Metabolism Disrupting Compounds

Author(s): Juliette Legler, Daniel Zalko, Fabien Jourdan, Miriam Jacobs, Bernard Fromenty, Patrick Balaguer, William Bourguet, Vesna Munic Kos, Angel Nadal, Claire Beausoleil, Susana Cristobal, Sylvie Remy, Sibylle Ermler, Luigi Margiotta-Casaluci, Julian L. Griffin, Bruce Blumberg, Christophe Chesné, Sebastian Hoffmann, Patrik L. Andersson, Jorke H. Kamstra
Published in: International Journal of Molecular Sciences, Issue 21/10, 2020, Page(s) 3480, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms21103480

Drug-induced hepatic steatosis in absence of severe mitochondrial dysfunction in HepaRG cells: proof of multiple mechanism-based toxicity

Author(s): Julien Allard, Simon Bucher, Julie Massart, Pierre-Jean Ferron, Dounia Le Guillou, Roxane Loyant, Yoann Daniel, Youenn Launay, Nelly Buron, Karima Begriche, Annie Borgne-Sanchez, Bernard Fromenty
Published in: Cell Biology and Toxicology, 2020, ISSN 0742-2091
Publisher: Kluwer Academic Publishers
DOI: 10.1007/s10565-020-09537-1

Cytochrome P450 2E1 should not be neglected for acetaminophen-induced liver injury in metabolic diseases with altered insulin levels or glucose homeostasis

Author(s): Julie Massart, Karima Begriche, Bernard Fromenty
Published in: Clinics and Research in Hepatology and Gastroenterology, 2020, ISSN 2210-7401
Publisher: Elsevier Masson
DOI: 10.1016/j.clinre.2020.05.018

Prenatal Exposure to Metabolism-Disrupting Chemicals, Cord Blood Transcriptome Perturbations, and Birth Weight in a Belgian Birth Cohort

Author(s): Anran Cai; Lützen Portengen; Gökhan Ertaylan; Juliette Legler; Roel Vermeulen; Virissa Lenters; Sylvie Remy
Published in: International Journal of Molecular Sciences, Issue Volume 24; Issue 8; Pages: 7607, 2023, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms24087607

Interspecies Differences in Activation of Peroxisome Proliferator-Activated Receptor γ by Pharmaceutical and Environmental Chemicals.

Author(s): Clémentine Garoche; Abdelhay Boulahtouf; Marina Grimaldi; Barbara Chiavarina; Lucia Toporova; Marjo J. den Broeder; Juliette Legler; William Bourguet; Patrick Balaguer
Published in: Environmental Science and Technology, Issue 1, 2021, ISSN 1520-5851
Publisher: American Chemical Society
DOI: 10.1021/acs.est.1c04318

Predicting Endocrine Disruption Using Conformal Prediction −A Prioritization Strategy to Identify Hazardous Chemicals withConfidence

Author(s): Maria Sapounidou, Ulf Norinder, Patrik L. Andersson
Published in: Chemical Research in Toxicology, 2022, ISSN 0893-228X
Publisher: American Chemical Society
DOI: 10.1021/acs.chemrestox.2c00267

Evidenced-Based Approaches to Support the Development of Endocrine-Mediated Adverse Outcome Pathways: Challenges and Opportunities

Author(s): Karine Audouze; Elias Zgheib; Khaled Abass; Khaled Abass; Asma H. Baig; Isabel Forner-Piquer; Henrik Holbech; Dries Knapen; Pim E. G. Leonards; Diana I. Lupu; Saranya Palaniswamy; Arja Rautio; Maria Sapounidou; Olwenn V. Martin
Published in: 2673-3080, Issue 5, 2021, ISSN 2673-3080
Publisher: Frontiers
DOI: 10.3389/ftox.2021.787017

Cryo-EM structure of the agonist-bound Hsp90-XAP2-AHR cytosolic complex

Author(s): Jakub Gruszczyk, Loïc Grandvuillemin, Josephine Lai-Kee-Him, Matteo Paloni, Christos G. Savva, Pierre Germain, Marina Grimaldi, Abdelhay Boulahtouf, Hok-Sau Kwong, Julien Bous, Aurélie Ancelin, Cherine Bechara, Alessandro Barducci, Patrick Balaguer, William Bourguet
Published in: Nature Communications, 2022, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-022-34773-w

High throughput screening of bisphenols and their mixtures under conditions of low-intensity adipogenesis of human mesenchymal stem cells (hMSCs)

Author(s): Kalle Norgren, Astrud Tuck, Antero Vieira Silva, Paula Burkhardt, Mattias Öberg, Vesna Munic Kos
Published in: Food and Chemical Toxicology, 2022, ISSN 0278-6915
Publisher: Elsevier BV
DOI: 10.1016/j.fct.2022.112842

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