Precision modelling of FHHNC using patient-derived kidney organoids for mechanistic and therapeutic discovery VHIR is seeking an outstanding and highly motivated postdoctoral researcher to apply for a Marie Sklodowska-Curie Postdoctoral Fellowship and join the Kidney Pathophysiology Research Group.

Marie Skłodowska-Curie Actions – Postdoctoral Fellowships (MSCA-PF) The Marie Skłodowska-Curie Postdoctoral Fellowships (MSCA-PF) are part of the Horizon Europe programme and support postdoctoral researchers in developing an original research and innovation project through international mobility. The programme aims to strengthen researchers’ careers through excellent science, international collaboration and interdisciplinary experience, while fostering integration in both academic and non-academic environments.

The MSCA-PF call is highly competitive and represents an excellent opportunity to attract international talent and support researchers in consolidating their scientific careers through an ambitious mobility-based fellowship. The 2026 call closes on 09/09/2026 (17:00 Brussels time). For candidates applying to a European Postdoctoral Fellowship, the fellowship duration is from 12 to 24 months .

Full eligibility details: MSCA Postdoctoral Fellowships 2026 Background Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a devastating ultra-rare renal tubulopathy caused by loss-of-function mutations in CLDN16 and CLDN19. The disease leads to severe magnesium and calcium wasting, nephrocalcinosis, and progressive chronic kidney disease, often culminating in renal failure at a young age. Additionally, patients carrying CLDN19 mutations develop early-onset ocular defects, causing lifelong visual impairment.

Despite its severity, no disease-modifying therapies or specific prognostic biomarkers are currently available. A striking feature of FHHNC is its marked phenotypic variability, even among siblings carrying identical mutations, particularly in Southern European patients harbouring the prevalent CLDN19 founder mutation p. G20D. This suggests the involvement of additional molecular mechanisms, including modifier genes and dysregulated pathways, which remain poorly understood.

Our group has established one of the largest and best-characterised FHHNC cohorts worldwide and pioneered an interdisciplinary strategy combining clinical research, molecular profiling, and artificial intelligence to uncover mechanisms and therapeutic opportunities in FHHNC. Using patient-derived molecular data integrated with AI-based network medicine approaches, we identified novel phenotype modifier genes, disease-associated urinary exosomal miRNA signatures, and multiple candidate drugs and synergistic drug combinations with therapeutic potential.

Building on these findings, we recently generated induced pluripotent stem cells (iPSC) from two siblings carrying the homozygous CLDN19 p. G20D mutation but displaying markedly divergent renal and ocular phenotypes. Together with our unique CLDN19 p. G20D knock-in mouse model, these resources provide an unprecedented platform to investigate FHHNC pathophysiology.

In this project, patient-derived genetically engineered kidney organoids will be used as advanced human 3D models to dissect disease mechanisms, understand phenotypic variability, and evaluate therapeutic candidates in a precision medicine framework. By integrating stem cell technology, genome engineering, and translational nephrology, this project aims to deliver transformative insights and accelerate therapeutic innovation for this unmet rare disease.

Objective The main goal of this project is to develop and exploit genetically engineered patient-derived kidney organoids to unravel the molecular mechanisms driving FHHNC, with a particular focus on phenotypic variability and sex-specific disease mechanisms, and to accelerate the identification of novel precision medicine strategies through drug repurposing and advanced human disease modelling.

Our Group The Kidney Pathophysiology Research Group at VHIR focuses on understanding the molecular and cellular mechanisms underlying rare and chronic kidney diseases, with a special emphasis on inherited tubulopathies, epithelial dysfunction, fibrosis, and the progression of chronic kidney disease. The group develops highly translational research programs integrating clinical data, experimental biology, and computational approaches to identify disease mechanisms and novel therapeutic opportunities.

One of the group’s main research lines focuses on Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC), an ultra-rare inherited renal disease caused by mutations in CLDN16 and CLDN19 . Over the last decade, the group has established one of the largest and best-characterised FHHNC patient cohorts worldwide and pioneered interdisciplinary approaches combining molecular biology, artificial intelligence, and translational nephrology to investigate disease progression and therapeutic strategies.

The group has generated unique experimental platforms, including patient-derived iPSC lines and the first CLDN19 p. G20D knock-in mouse model available for FHHNC research. In parallel, strong collaborations with clinicians, computational scientists, and patient advocacy organisations ensure a highly collaborative, multidisciplinary, and patient-oriented research environment with direct translational impact.

Main responsibilities and duties: Preparation of an MSCA proposal focused on translational research in rare renal diseases using advanced in vitro , ex vivo , and in vivo models The project will combine stem cell technology, functional genomics, disease modelling, and therapeutic evaluation in the context of inherited renal tubulopathies and epithelial dysfunction.

Work within a multidisciplinary and highly translational environment integrated into the Paediatric Nephrology Service of the Vall d’Hebron University Hospital Close interaction between clinicians and basic researchers, providing a unique framework to translate experimental discoveries into clinically relevant applications.