Identifying multiscale translational safety biomarkers using a network-based systems approach

Autor: Giulia Callegaro, Johannes P. Schimming, Janet Piñero González, Steven J. Kunnen, Lukas Wijaya, Panuwat Trairatphisan, Linda van den Berk, Kim Beetsma, Laura I. Furlong, Jeffrey J. Sutherland, Jennifer Mollon, James L. Stevens, Bob van de Water

Publikováno v: iScience, Vol 26, Iss 3, Pp 106094- (2023)

Summary: Animal testing is the current standard for drug and chemicals safety assessment, but hazards translation to human is uncertain. Human in vitro models can address the species translation but might not replicate in vivo complexity. Herein, we

Externí odkaz: https://doaj.org/article/c1ec17ac979040d09bc96f5bae7f9e91

A systems approach reveals species differences in hepatic stress response capacity

Autor: Giusy Russomanno, Rowena Sison-Young, Lucia A. Livoti, Hannah Coghlan, Rosalind E. Jenkins, Steven J. Kunnen, Ciarán P. Fisher, Dennis Reddyhoff, Iain Gardner, Adeeb H. Rehman, Stephen W. Fenwick, Andrew R. Jones, Guy Vermeil De Conchard, Gilles Simonin, Helene Bertheux, Richard J. Weaver, Michael J. Liguori, Diana Clausznitzer, James L. Stevens, Christopher E. Goldring, Ian M. Copple

To minimise unexpected toxicities in early phase clinical studies of new drugs, it is vital to understand fundamental similarities and differences between preclinical test species and humans. We have used physiologically-based pharmacokinetic modelli

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::681d5b219b7f1f608f9ac0467a0f6f7c
https://doi.org/10.1101/2022.04.13.488145

Inflammation-associated suppression of metabolic gene networks in acute and chronic liver disease

Autor: Rajanikanth Vadigepalli, Jan B. Hoek, Agata Widera, Daniela González, Cristina Cadenas, Karolina Edlund, Benjamin K. Banhart, Jan G. Hengstler, Larissa Pütter, Reinhard Guthke, Patricio Godoy, David C. Hay, Rosemarie Marchan, James L. Stevens, G Campos, Jeffrey Willy, Catherine M. Verfaillie, Wolfgang Schmidt-Heck, Thomas S. Weiß, Jonathan De Smedt, Claudio Hetz, Agapios Sachinidis, Michael Schwarz, Ahmed Ghallab, Albert Braeuning

Publikováno v: Campos, G, Schmidt-Heck, W, De Smedt, J, Widera, A, Ghallab, A, Pütter, L, González, D, Edlund, K, Cadenas, C, Marchan, R, Guthke, R, Verfaillie, C, Hetz, C, Sachinidis, A, Braeuning, A, Schwarz, M, Weiß, T S, Banhart, B K, Hoek, J, Vadigepalli, R, Willy, J, Stevens, J L, Hay, D C, Hengstler, J G & Godoy, P 2020, ' Inflammation-associated suppression of metabolic gene networks in acute and chronic liver disease ', Archives of toxicology, vol. 94, pp. 205–217 . https://doi.org/10.1007/s00204-019-02630-3
Archives of Toxicology

Inflammation has been recognized as essential for restorative regeneration. Here, we analyzed the sequential processes during onset of liver injury and subsequent regeneration based on time-resolved transcriptional regulatory networks (TRNs) to under

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::70d21dc79559148525ec23b598635c7c
https://doi.org/10.1007/s00204-019-02630-3

A Novel Open Access Web Portal for Integrating Mechanistic and Toxicogenomic Study Results

Autor: Yue Webster, Jeffrey J. Sutherland, Kamin J. Johnson, James L. Stevens, Bradley J. Mills, Daniel H. Robertson, Navin Elango

Publikováno v: Toxicological Sciences

Applying toxicogenomics to improving the safety profile of drug candidates and crop protection molecules is most useful when it identifies relevant biological and mechanistic information that highlights risks and informs risk mitigation strategies. P

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3e20b77e0f1f84a2d1da41b85b3c2475
https://doi.org/10.1093/toxsci/kfz101

Integration of temporal single cell cellular stress response activity with logic-ODE modeling reveals activation of ATF4-CHOP axis as a critical predictor of drug-induced liver injury

Autor: Ariadna Alcalà Morera, Attila Gábor, Huan Yang, Stefan Schildknecht, Julio Saez-Rodriguez, Hennicke Kamp, Sylvia E. Le Dévédec, Peter Bouwman, Marcel Leist, Jan G. Hengstler, Joost B. Beltman, Panuwat Trairatphisan, Bob van de Water, Kirsten E. Snijders, Jason Keet, Marije Niemeijer, Lukas S Wijaya, James L. Stevens, Steven Wink

Publikováno v: Biochemical Pharmacology
Biochemical Pharmacology, 190
Biochemical pharmacology, 190:114591

Drug-induced liver injury (DILI) is the most prevalent adversity encountered in drug development and clinical settings leading to urgent needs to understand the underlying mechanisms. In this study, we have systematically investigated the dynamics of

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::381c7cd9b5f7fb2375f99d72a85e5071