Modeling is fundamental to drug development. But there is the need to develop innovative methodologies and practices to integrate the ‘omics analysis and network analysis with quantitative mechanism-based models to form a new approach to drug safety assessment. The emerging field of Quantitative Systems Pharmacology (QSP) seeks to address this methodological gap via the development of mathematical models that account for the mechanisms underlying the response of integrated biological systems at the level of target cells and organs.Scope:
The scope of this proposal is to 1) develop Quantitative Systems Toxicology (QST) models for drug-induced toxicity with the focus on four different organ systems: Heart, Liver, Kidney and the Gastrointestinal (GI)-immune system, and 2) use this QST approach for the prediction of clinical toxicity using preclinical data.Expected Impact:
The results of this action will help to address the needs of the toxicology community for more comprehensive coverage of mechanistic toxicity pathways from which to define a mechanism-based screening approach.