This paper introduces a three-step workflow using segmented regression to improve semi-mechanistic pharmacodynamic modeling of antibiotic effects, demonstrating it with colistin against Pseudomonas aeruginosa.

bioRxiv · Nov 4, 2026 · PreprintPharmacology & Toxicology

Accelerating drug development in infectious diseases using zebrafish disease models supported by pharmacokinetic pharmacodynamic modeling as new approach methodology (NAM)

Gabriel Forn‐Cuní, Bart van Lieshout, Bjørn E. V. Koch, Cristina Villellas, Stijn Van Asten, Dina Berlina, Ellen Lanckacker, Bart Stoops, Rob J. Vreeken, Dirk Roymans, Elke H. J. Krekels, J. G. Coen van Hasselt, Herman P. Spaink, Rob Christiaan van Wijk

Zebrafish larva infection experiments plus pharmacokinetic-pharmacodynamic (PKPD) modelling gave bedaquiline's in vivo Emax and EC50 against M. marinum in about 2 months; waterborne clarithromycin barely entered larvae.

bioRxiv · Oct 30, 2026 · PreprintPharmacology & Toxicology✦ In-depth digest

Collateral effects of bacteriophage resistance on antibiotic sensitivity in Pseudomonas aeruginosa

Laura R. Baars, Karsten Nagel, Laura B. Zwep, Tingjie Guo, J. G. Coen van Hasselt

This study examines how phage resistance in Pseudomonas aeruginosa affects antibiotic sensitivity, finding strain- and antibiotic-specific collateral effects.

bioRxiv · Oct 16, 2026 · PreprintPharmacology & Toxicology

Pharmacodynamic modeling of colistin and imipenem against in vitro Pseudomonas aeruginosa biofilms

Yuchen Guo, Jinqiu Yin, Linda B. S. Aulin, Oana Ciofu, Claus Ernst Moser, Parth J. Upadhyay, Niels Høiby, Hengzhuang Wang, Tingjie Guo, J. G. Coen van Hasselt

This study develops a PK-PD model for imipenem and colistin against Pseudomonas aeruginosa biofilms to optimize clinical dosing schedules.

Biofilm · Aug 3, 2026Peer-reviewedPharmacology & Toxicology

From exact gradients to exact standard errors: third- and fourth-order sensitivities for the Laplacian population likelihood family

Hidde van de Beek, Massinissa Beldjenna, Matthew L. Fidler, Laura B. Zwep, J. G. Coen van Hasselt

This paper derives exact standard errors for Laplacian population likelihood models using third- and fourth-order sensitivities, avoiding finite differencing and empirical Bayes reoptimization.

bioRxiv · Jul 15, 2026 · PreprintPharmacology & Toxicology

A Novel Hollow Fiber Infection Model (HFIM) for Antiviral PK/PD studies of CMV infection.

Lalitya M. Sudarsono, Suzanne A M Wenker, Xuanlin Liu, Jorn Brink, Dirk-Jan van den Berg, J. G. Coen van Hasselt, Anne‐Grete Märtson

This paper introduces a novel hollow fiber infection model (HFIM) for PK/PD studies of ganciclovir in CMV infection, enabling reliable drug exposure and viral dynamics analysis.

Antimicrobial Agents and Chemotherapy · Jun 18, 2026Peer-reviewedPharmacology & Toxicology

The influence of heteroresistance, growth and antibiotic selection in shaping the invasion dynamics of colistin resistant Pseudomonas aeruginosa

Angie C. Alarcon Rios, Anh Duc Pham, Catherijne A. J. Knibbe, Daniel E. Rozen, J. G. Coen van Hasselt, Linda B. S. Aulin

This study examines how heteroresistance, growth rates, and antibiotic selection affect the invasion dynamics of colistin-resistant Pseudomonas aeruginosa in co-culture with susceptible isolates.

FEMS Microbiology Letters · Jan 1, 2026Peer-reviewedMicrobiology

Aggregate data modelling: a fast implementation for fitting pharmacometrics models to summary-level data in R

Hidde van de Beek, Pyry A. J. Välitalo, J. G. Coen van Hasselt, Laura B. Zwep

The paper implements an aggregate data modelling framework in R, introducing an efficient algorithm that significantly speeds up pharmacometric model fitting while maintaining accuracy.

Journal of Pharmacokinetics and Pharmacodynamics · Dec 9, 2025Peer-reviewedPharmacology & Toxicology

Late treatment initiation leads to reduced antiviral potency

Xuanlin Liu, Evelyn J. Franco, Sean N. Avedissian, Kaley C. Hanrahan, Jérémie Guedj, J. G. Coen van Hasselt, Ashley N. Brown, Anne‐Grete Märtson

This study shows that late antiviral treatment initiation reduces drug potency (EC50), and a time-varying EC50 model better fits viral load data than a constant EC50 model.

bioRxiv · Sep 24, 2025 · PreprintPharmacology & Toxicology

Divergent spontaneous antibiotic-resistance evolution confers reciprocal and exploitable collateral sensitivity effects

Apostolos Liakopoulos, Sebastian Tommi Tandar, Irene V Hoogendijk, Efthymia Fragkiskou, Zheren Zhang, Bastienne Vriesendorp, Linda B. S. Aulin, J. G. Coen van Hasselt, Daniel E. Rozen

This study identifies consistent collateral sensitivity interactions between antibiotics in S. pneumoniae and develops a model to guide treatment strategies.

bioRxiv · Sep 22, 2025 · PreprintMicrobiology

The endocannabinoid 2-arachidonoylglycerol is released and transported on demand via extracellular microvesicles

Verena M. Straub, Benjámin Barti, Sebastian Tommi Tandar, Anna Floor Stevens, Noëlle van Egmond, Tom van der Wel, Na Zhu, Joel Rüegger, Cas van der Horst, Laura H. Heitman, Yulong Li, Nephi Stella, J. G. Coen van Hasselt, István Katona, Mario van der Stelt

The paper proposes an on-demand release model for endocannabinoid 2-AG via microvesicles, showing stimulus-dependent release regulated by PKC, DAGL, and Arf6.

Proceedings of the National Academy of Sciences · Feb 20, 2025Peer-reviewedNeuroscience

Interspecies interactions alter the antibiotic sensitivity of Pseudomonas aeruginosa

Catharina I. M. Koumans, Sebastian Tommi Tandar, Apostolos Liakopoulos, J. G. Coen van Hasselt

This study quantifies how interspecies interactions affect antibiotic sensitivity of Pseudomonas aeruginosa in polymicrobial infections and shows these interactions can alter treatment effectiveness.

Microbiology Spectrum · Nov 4, 2024Peer-reviewedPharmacology & Toxicology

Quantitative Systems Pharmacology Modeling Framework of Autophagy in Tuberculosis: Application to Adjunctive Metformin Host-Directed Therapy

Krina Mehta, Tingjie Guo, Robert S. Wallis, Piet H. van der Graaf, J. G. Coen van Hasselt

This paper develops a QSP framework to evaluate metformin's effect on autophagy in tuberculosis, showing limited but dose-dependent benefits in reducing bacterial load and inflammation.

Antimicrobial Agents and Chemotherapy · Jul 14, 2022Peer-reviewedSystems Biology

Protein structure-based gene expression signatures

Rayees Rahman, Nicole Zatorski, Jens Hansen, Yuguang Xiong, J. G. Coen van Hasselt, Eric A. Sobie, Marc R. Birtwistle, Evren U. Azeloglu, Ravi Iyengar, Avner Schlessinger

This paper introduces structural gene expression signatures (sGES) derived from protein structure features, showing their utility in identifying robust biological signatures across datasets and experimental platforms.

Proceedings of the National Academy of Sciences · May 3, 2021Peer-reviewedBioinformatics

A tissue- and organ-based cell biological atlas of obesity-related human genes and cellular pathways

Iman Tavassoly, Valentina Barbieri, J. G. Coen van Hasselt, Pedro Martinez, Eric A. Sobie, Jens Hansen, Evren U. Azeloglu, Joseph Goldfarb, Philippe Sanséau, Deepak K. Rajpal, Ravi Iyengar

The paper constructs a tissue- and organ-based subcellular-function atlas of obesity-related genes and pathways using publicly available datasets and integration methods.

bioRxiv · Mar 16, 2020 · PreprintSystems Biology

A Comparison of mRNA Sequencing with Random Primed and 3’-Directed Libraries

Yuguang Xiong, Magali Soumillon, Jie Wu, Jens Hansen, Bin Hu, J. G. Coen van Hasselt, Gomathi Jayaraman, Ryan G. Lim, Mehdi Bouhaddou, Loren Ornelas, Jim Bochicchio, Lindsay Lenaeus, Jennifer T. Stocksdale, Jaehee V. Shim, Emilda Gomez, , Marc R. Birtwistle

This study compares 3-DGE and conventional mRNAseq, finding similar gene expression results with 3-DGE offering cost savings and scalability.

Scientific Reports · Nov 1, 2017Peer-reviewedGenomics