Research project

Quantitative Systems Pharmacology

This research area is focused on the development and application of novel concepts and models in the emerging area of quantitative systems pharmacology (QSP).

Contact: Piet Hein van der Graaf

QSP has been described as the “quantitative analysis of the dynamic interactions between drug(s) and a biological system that aims to understand the behaviour of the system as a whole”[1]. In our work we focus on developing models and approaches that facilitate the understanding of the key mechanisms and dynamics of drug disposition, drug target interaction, and signal transduction that ultimately lead to a drug response measured in a model system or in patients. We expect that QSP approaches can improve the accuracy and efficiency of translational approaches in drug development, and as such may reduce attrition during early clinical development. Secondly, we expect that QSP approaches can lead to developing further understanding of the underlying mechanisms of inter-patient variability, and as such inform efforts in personalized medicine. Through the projects in this research area, we aim to integrate the analysis of experimental and clinical data with prior knowledge in order to develop mathematical models that can adequately capture the complexity that determine drug response. In our work we are both interested to explore more fundamental concepts of the analysis of nonlinear systems and receptor-ligand kinetics, as well as developing applied models to different therapeutic areas including neuroendocrine response, amyotrophic lateral sclerosis, immunology, infectious diseases and oncology.

Within LACDR’s cluster Systems Pharmacology we collaborate intensively with the Analytical Biosciences division around the application and integration of metabolomics-based biomarker discovery. In addition we collaborate with the Institute of Biology at Leiden University on the use of a zebrafish model as translational systems pharmacology-based model for predicting drug pharmacokinetics. Finally we have well established collaborations with the Mathematical Institute, also at Leiden University, around the theme of mathematical pharmacology and the application of advanced mathematical analysis in the area of pharmacology.

van der Graaf P.H. & Benson N. Systems pharmacology: bridging systems biology and pharmacokinetics-pharmacodynamics (PKPD) in drug discovery and development. Pharm. Res. 28, 1460–1464 (2011).

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