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Functional Measurements IN-THE-KIDNEY to Diagnose, Understand and Treat Renal Tubulopathies

Objective

BACKGROUND | Renal tubulopathies are a large group of genetic disorders that disturb the function of the kidney tubule. A major challenge for diagnostics and treatment of magnesium (Mg2+) wasting tubulopathies, is absence of functional cell models and tools to study the pathophysiology. Diagnostics of hereditary Mg2+ wasting tubulopathies based on genetic screening, rather than biological measurements of kidney processes. Therapy largely depends on oral supplements because therapeutics that target the cause of disease are not available. VISION | In my vision, better insights in the cellular functional processes in the kidney are the next essential step forward towards better diagnostics, pathophysiological understanding and development of therapy. Development of functional Mg2+ transport measurements and innovative use of patient-specific models is required to increase diagnostic yield and to develop therapy. AIMS AND APPROACH | In this project, I aim to develop a urine-based diagnostic approach using scRNA sequencing and extracellular vesicle proteomics to provide biological diagnosis of renal tubulopathies. Using urine-derived adult stem cells, I will perform the first ever functional studies of ion reabsorption in kidney organoids. This approach allows personalized analysis of the pathophysiology as well as patient-specific drug screenings. Lastly, I will be the first to apply intravital multiphoton imaging in mice to measure Mg2+ reabsorption in the kidney tubule. The combination of patient-derived organoids and mice models will be used to test novel therapeutics. IMPACT AND INNOVATION | IN-THE-KIDNEY establishes the novel concept of biological diagnostics for renal tubulopathies, develops for the first-time patient-derived tissue models for functional analysis and introduces intravital ion transport measurements in mice. The methodology and approaches in this project will result in the identification of novel therapeutics for Mg2+-wasting tubulopathies.

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2021-STG

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Host institution

STICHTING RADBOUD UNIVERSITAIR MEDISCH CENTRUM
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.

€ 1 500 000,00
Address
GEERT GROOTEPLEIN 10 ZUID
6525 GA NIJMEGEN
Netherlands

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Region
Oost-Nederland Gelderland Arnhem/Nijmegen
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.

€ 1 500 000,00

Beneficiaries (1)

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