Freddy Van Goethem

Molecular smugglers in obesity-driven MASLD: snitching on adipose-derived extracellular vesicles

Qiuyang Chen, Taisiia Shevchenko, Dewen Zhan, Ningning Ma et autres

Human stem cell-derived hepatic cells recapitulate polygenic risk in MASLD development and highlight CD36 as a key mediator

Alexandra Gatzios, Marth Stinckens, Anouk Verhoeven, Matthias Rombaut et autres

Several genetic variants have been identified that impact outcomes in patients with metabolic dysfunction-associated steatohepatitis (MASH), but cellular platforms to identify molecular targets for treatment remain scarce. This study aims to employ a polygenic risk score for hepatic fat content (PRS-HFC) in …

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Advancing Genotoxicity Assessment by Building a Global AOP Network

Emmanuel Demuynck, Tamara Vanhaecke, Anouck Thienpont, Davie Cappoen et autres

Current genotoxicity testing strategies face several challenges, including a high incidence of misleading positive results that lead to unnecessary animal testing, limited mechanistic insights, insufficient integration of innovative methodologies, and a lack of quantitative assessment. Despite rapid advancements in technology and scientific …

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In vitro to in vivo extrapolation modeling to facilitate the integration of transcriptomics data into genotoxicity assessment

Anouck Thienpont, Eunnara Cho, Andrew Williams, Matthew J. Meier et autres

). High-throughput toxicokinetic models estimated the human AEDs for these tPoDs, which were compared with (a) previously reported genotoxicity-specific AEDs from other New Approach Methodologies, and (b) in vivo PoDs from animal studies. We found that the generic AEDs were more conservative …

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Optimization of the drug-induced cholestasis index based on advanced modeling for predicting liver toxicity

Annika Drees, Vahid Nassiri, Andrés Tabernilla, Jan Serroyen et autres

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Next generation risk assessment of hair dye HC yellow no. 13: Ensuring protection from liver steatogenic effects

Sara Sepehri, Dinja De Win, Anja Heymans, Freddy Van Goethem et autres

This study employs animal-free Next Generation Risk Assessment (NGRA) principles to evaluate the safety of repeated dermal exposure to 2.5% (w/w) HC Yellow No. 13 (HCY13) hair dye. As multiple in silico tools consistently flagged hepatotoxic potential, likely due to HCY13's trifluoromethyl …

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A global AOP network for genotoxicity to drive the integration of NAMs

Emmanuel Demuynck, Tamara Vanhaecke, Anouck Thienpont, Davie Cappoen et autres

Current genotoxicity testing strategies face several challenges, including a high incidence of misleading positive results that lead to unnecessary animal testing, limited mechanistic insights, insufficient integration of innovative methodologies, and a lack of quantitative assessment. Despite rapid advancements in technology and scientific …

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P01-23 Optimization of predictive liver toxicity modeling based on the drug-induced cholestasis index

Alfred Drees, Vahid Nassiri, A. Tabernilla Garcia, Jan Serroyen et autres

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Gene Regulatory Network Based Toxicity Classification and Prediction: A DILI Case Study

Shreyas U. Hirway, Fetene B. Tekle, Thomas de Marchin, Onyi Irrechukwu et autres

Drug development is a complex process that requires a rigorous safety assessment. The risk assessment on liver, which plays a central role in drug metabolism in the body, can have a huge impact on drug development. Drug induced liver injury (DILI) has …

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P16-06: High-content imaging of human hepatic spheroids for studying compounds with cholestatic liability

Bruna dos Santos Rodrigues, X. Cendoya Garmendia, Margino Steemans, Emmanuel M. Gustin et autres

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P16-33: Identifying and characterizing toxicity liabilities of pharmaceuticals using ToxProfiler: A blinded case study with the ITLF consortium

Bas ter Braak, Liesanne Wolters, Kim Elbertse, Mario Beilmann et autres

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AI/ML Models to Predict the Severity of Drug-Induced Liver Injury for Small Molecules

Mohan S. Rao, Vahid Nassiri, Cristóbal Alhambra, Jan Snoeys et autres

Drug-induced liver injury (DILI), believed to be a multifactorial toxicity, has been a leading cause of attrition of small molecules during discovery, clinical development, and postmarketing. Identification of DILI risk early reduces the costs and cycle times associated with drug development. In …

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