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HemaTrax: Lineage-resolved prediction of hematotoxicity for human-relevant drug development

Objective

Hematotoxicity is a major determinant of treatment intensity and dosing in cancer therapy and a frequent cause of late-stage attrition in drug development. Current pre-clinical assessment strategies provide limited mechanistic insight into how drugs perturb human hematopoiesis. Animal models often translate poorly to human lineage sensitivities and rely on late aggregate outcomes, such as cytopenias, while human in-vitro assays typically lack bone-marrow niche context. As a result, lineage-specific toxicity mechanisms remain difficult to anticipate, particularly for complex or combination therapies.

This project will test a mechanism-informed framework (HemaTrax) for predicting hematotoxicity. HemaTrax integrates human hematopoietic niche co-culture systems with early lineage-resolved single-cell profiling and computational modelling of gene-regulatory perturbations. Drug-induced changes in transcription-factor activity detected at early differentiation stages will be mapped onto lineage-specific regulatory programmes derived from a large human bone-marrow reference atlas to predict downstream hematopoietic effects.
The main objective is to determine whether early transcription-factor perturbations predict clinically observed hematotoxicity patterns. Model-derived predictions will be systematically benchmarked against longitudinal hematological data from retrospective patient cohorts treated with selected chemotherapeutic agents.

If successful, this framework will establish a human-relevant and mechanistically interpretable basis for hematotoxicity assessment, enabling improved pre-clinical decision-making and informing the design of prospective clinical validation studies. More broadly, the approach supports regulatory efforts to increase human relevance while reducing reliance on animal experimentation.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2026-POC

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Host institution

UNIVERSITAT BASEL
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 150 000,00
Address
PETERSPLATZ 1
4051 Basel
Switzerland

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Region
Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

No data

Beneficiaries (1)