HORIZON-HLTH-2027-01-CARE-02.Mechanistic resolution of adverse drug reactions in polypharmacy through proteome-wide interaction mapping

We bring extensive experience in European collaborative research as both coordinator and partner, with a strong track record in environmental and biomedical proteomics, multi-omics integration, and mechanistic toxicology.

We contribute a mechanistic understanding of adverse drug reactions (ADRs) arising from multiple medications by identifying protein-level interactions, pathway perturbations, and early biological responses to drug combinations.

Adverse drug reactions in polypharmacy are driven by complex drug–drug and drug–host interactions, which remain poorly understood using current approaches largely based on clinical observation, pharmacogenomics, and statistical associations . This limits the ability to predict, prevent, and manage ADRs effectively.

Our approach is based on high-throughput proteome-wide interaction profiling (PISA), enabling the identification of molecular initiating events from single drugs and their combinations, including unexpected off-target effects. This allows us to:

• Map drug–protein interaction landscapes under polypharmacy conditions

• Identify pathway-level perturbations and emergent effects specific to drug combinations

• Detect early molecular signatures of ADRs prior to clinical manifestation

• Support the discovery of mechanistically grounded biomarkers for patient stratification

This approach complements pharmacogenomics by capturing functional biochemical interactions and supports integration with clinical data, electronic health records, and AI-based decision support systems.

We aim to contribute as partner and potential Work Package leader, focusing on:

• Mechanistic mapping of ADRs in polypharmacy

• Biomarker discovery and validation

• Integration of multi-omics with clinical and pharmacological data

By linking drug exposure to biological function, we provide the causal layer necessary to understand and predict ADRs, supporting safer and more effective medication management, reducing prescription cascades, and enabling personalised treatment strategies.