The Kuepfer group combines physiologically-based pharmacokinetic (PBPK) modelling at the whole-body level with systems biology effect models at the cellular and tissue scale. The resulting multiscale models are used for the analyses of organ systems such as the gut-liver-axis as well as in applications of quantitative systems pharmacology and toxicology.
Lars Kuepfer studied chemical engineering at the TH Karlsruhe, RWTH Aachen and Carnegie Mellon University, Pittsburgh, and received his Ph.D. degree from ETH Zurich. In his thesis, Lars Kuepfer analyzed metabolic and regulatory principles in yeast based on computational models. In 2005, he joined Bayer AG, where he worked on pharmacokinetic and pharmacodynamic modeling of novel drug candidates to support decision making along the pharma development process. In addition, Lars Kuepfer also started as a group leader at the Institute of Applied Microbiology of the RWTH Aachen in 2011. In 2021, he became professor for systems medicine with focus on organ interactions. Lars Kuepfer’s main research interests are in the areas of physiologically-based pharmacokinetic (PBPK) modelling, systems biology as well as pharmacology and toxicology.
Zita Soons is a postdoctoral researcher in systems biology of human and microbial metabolism. She develops and applies metabolic models aimed at mechanistic understanding of bio(medical) processes. To this end, she collaborates with experimental and medical groups. At RWTH, she integrates metabolic pathway analysis with physiologically-based pharmacokinetic (PBPK) modelling applied to the microbiome and the kidney. Zita studied biotechnology at Wageningen University. Her dissertation represents computational work at the Systems and Control Group and lab experiments at the Netherlands Vaccine Institute. She obtained a grant for a postdoc on metabolic modelling at the University of Minho (Portugal) in 2009–2012, which involved a six month visit at EMBL Heidelberg. Next, she pursued a postdoc at the DKFZ/Heidelberg University. She taught her first courses at the Department of Knowledge Engineering of Maastricht University and worked as assistant professor at the Department of Surgery of MUMC+ (The Netherlands) until 2020.
Rebekka Fendt studied Molecular Medicine at the University of Göttingen and Systems Biology at Heidelberg University and the University of Gothenburg. Before she joined Lars Küpfers group at the University Hospital Aachen, she was a PhD student at the department for Systems Pharmacology & Medicine at Bayer AG. Rebekka‘s doctoral research focuses on the effect of chronic liver disease on pharmacokinetics. She applies physiologically based pharmacokinetic modeling approaches for data analysis and hypothesis testing. Her research interests also include signal transduction, dynamic pathway models, drug metabolism and personalized medicine.
Bastian Kister studied life sciences and molecular biosciences with a major in systems biology at the Ruprecht-Karl University, Heidelberg. In January 2020, he was recruited to RWTH Aachen for a PhD project within the CRC182 gut-liver axis. This project aims to apply computational physiologically-based modelling of bile acid metabolism at the whole-body level to gain a more mechanistic understanding of its underlying processes. Bastian Kister’s main interests lies in computational modelling which helps to understand bio(medical) processes on a mechanistic level and aids in the identification of parameters relevant in the assessment of patients and their corresponding treatment.
A workflow to build PBTK models for novel species. Schneckener S, Preuss TG, Kuepfer L, Witt J. Arch Toxicol. 2020 Nov;94(11):3847-3860. doi: 10.1007/s00204-020-02922-z. Epub 2020 Oct 9.
A Physiology-Based Model of Human Bile Acid Metabolism for Predicting Bile Acid Tissue Levels After Drug Administration in Healthy Subjects and BRIC Type 2 Patients. Baier V, Cordes H, Thiel C, Castell JV, Neumann UP, Blank LM, Kuepfer L. Front Physiol. 2019 Sep 27;10:1192. doi: 10.3389/fphys.2019.01192.
Using quantitative systems pharmacology to evaluate the drug efficacy of COX-2 and 5-LOX inhibitors in therapeutic situations. Thiel C, Smit I, Baier V, Cordes H, Fabry B, Blank LM, Kuepfer L. NPJ Syst Biol Appl. 2018 Aug 3;4:28. doi: 10.1038/s41540-018-0062-3.
Integration of genome-scale metabolic networks into whole-body PBPK models shows phenotype-specific cases of drug-induced metabolic perturbation. Cordes H, Thiel C, Baier V, Blank LM, Kuepfer L. NPJ Syst Biol Appl. 2018 Feb 26;4:10. doi: 10.1038/s41540-018-0048-1.
A model-based assay design to reproduce in vivo patterns of acute drug-induced toxicity. Kuepfer L, Clayton O, Thiel C, Cordes H, Nudischer R, Blank LM, Baier V, Heymans S, Caiment F, Roth A, Fluri DA, Kelm JM, Castell J, Selevsek N, Schlapbach R, Keun H, Hynes J, Sarkans U, Gmuender H, Herwig R, Niederer S, Schuchhardt J, Segall M, Kleinjans J. Arch Toxicol. 2018 Jan;92(1):553-555. doi: 10.1007/s00204-017-2041-7.
A Comparative Analysis of Drug-Induced Hepatotoxicity in Clinically Relevant Situations. Thiel C, Cordes H, Fabbri L, Aschmann HE, Baier V, Smit I, Atkinson F, Blank LM, Kuepfer L. PLoS Comput Biol. 2017 Feb 2;13(2):e1005280. doi: 10.1371/journal.pcbi.100528
Physiologically-based modelling in mice suggests an aggravated loss of clearance capacity after toxic liver damage. Schenk A, Ghallab A, Hofmann U, Hassan R, Schwarz M, Schuppert A, Schwen LO, Braeuning A, Teutonico D, Hengstler JG, Kuepfer L. Sci Rep. 2017 Jul 24;7(1):6224. doi: 10.1038/s41598-017-04574-z
Model-based contextualization of in vitro toxicity data quantitatively predicts in vivo drug response in patients. Thiel C, Cordes H, Conde I, Castell JV, Blank LM, Kuepfer L. Arch Toxicol. 2017 Feb;91(2):865-883. doi: 10.1007/s00204-016-1723-x
Multiscale modeling reveals inhibitory and stimulatory effects of caffeine on acetaminophen-induced toxicity in humans. Thiel C, Cordes H, Baier V, Blank LM, Kuepfer L. CPT Pharmacometrics Syst Pharmacol. 2017 Feb;6(2):136-146. doi: 10.1002/psp4.12153. Epub 2017 Jan 28.
Applied Concepts in PBPK Modeling: How to Build a PBPK/PD Model. Kuepfer L, Niederalt C, Wendl T, Schlender JF, Willmann S, Lippert J, Block M, Eissing T, Teutonico D. CPT Pharmacometrics Syst Pharmacol. 2016 Oct;5(10):516-531. doi: 10.1002/psp4.12134. Epub 2016 Oct 19.
Translational learning from clinical studies predicts drug pharmacokinetics across patient populations. Krauss M, Hofmann U, Schafmayer C, Igel S, Schlender J, Mueller C, Brosch M, von Schoenfels W, Erhart W, Schuppert A, Block M, Schaeffeler E, Boehmer G, Goerlitz L, Hoecker J, Lippert J, Kerb R, Hampe J, Kuepfer L, Schwab M. NPJ Syst Biol Appl. 2017 Mar 28;3:11. doi: 10.1038/s41540-017-0012-5.
A Physiologically Based Pharmacokinetic Model of Isoniazid and Its Application in Individualizing Tuberculosis Chemotherapy. Cordes H, Thiel C, Aschmann HE, Baier V, Blank LM, Kuepfer L. Antimicrob Agents Chemother. 2016 Sep 23;60(10):6134-45. doi: 10.1128/AAC.00508-16.
A systematic evaluation of the use of physiologically based pharmacokinetic modeling for cross-species extrapolation. Thiel C, Schneckener S, Krauss M, Ghallab A, Hofmann U, Kanacher T, Zellmer S, Gebhardt R, Hengstler JG, Kuepfer L. J Pharm Sci. 2015 Jan;104(1):191-206. doi: 10.1002/jps.24214.
Spatio-temporal simulation of first pass drug perfusion in the liver. Schwen LO, Krauss M, Niederalt C, Gremse F, Kiessling F, Schenk A, Preusser T, Kuepfer L. PLoS Comput Biol. 2014 Mar 13;10(3):e1003499. doi: 10.1371/journal.pcbi.1003499.
Integrating cellular metabolism into a multiscale whole-body model. Krauss M, Schaller S, Borchers S, Findeisen R, Lippert J, Kuepfer L. PLoS Comput Biol. 2012;8(10):e1002750. doi: 10.1371/journal.pcbi.1002750.