PhD Position (M/F) – Pathomechanisms of Vascular Calcification in Pediatric Chronic Kidney Disease (VASC-OPATH project)

Job Description

Thesis Subject

Chronic kidney disease (CKD) affects around 10% of the world's population and drives major vascular remodeling, including arterial stiffness, left ventricular hypertrophy and vascular calcification (VC). VC is a major cardiovascular complication of CKD, associated with a mortality risk up to 1000-fold higher than in the age-matched general population. Despite current treatments targeting mineral and bone disorders (CKD-MBD), VC progression is not effectively prevented, including after kidney transplantation.

While CKD-associated VC is extensively studied in adults, the underlying mechanisms remain poorly understood in children. Pediatric CKD nonetheless provides a unique model to study VC: the disease is most often caused by congenital abnormalities restricted to the kidney and urinary tract (CAKUT), without the systemic comorbidities (diabetes, smoking, ageing) that complicate interpretation in adults. Preliminary data from the team (multi-omics analyses of pediatric arterioles) identified a dysregulated molecular network involving the extracellular matrix and immune signalling, linking matrix remodelling and the Wnt/β-catenin pathway.

The VASC-OPATH project proposes a translational strategy combining the analysis of paediatric samples with the functional validation of the identified molecular mechanisms in an innovative in vitro model. The recruited PhD student will contribute to the three research axes of the project:
- Single-nuclei RNA sequencing (snRNAseq) of microdissected arterioles from children with normal kidney function and children with stage-5 CKD (before dialysis), to establish the cellular and molecular map of early paediatric vasculopathy (endothelial cells, smooth muscle cells, fibroblasts, immune cells including macrophages).
- Modelling of CKD-like vascular injury in 3D vascular organoids derived from induced pluripotent stem cells (iPSCs), exposed to phosphate, uremic toxins and pro-inflammatory cytokines, to characterise vascular remodelling, extracellular matrix changes and Wnt/β-catenin signalling.
- Functional validation through CRISPR/Cas9 gene knockout (isogenic iPSC lines) of target genes in the vascular organoid model, to establish a causal link between these target genes and the vascular calcification phenotype.

This PhD project, at the interface of vascular biology, immunology, stem cell biology and translational nephrology, aims to better understand the early cellular and molecular mechanisms of VC in order to identify new diagnostic biomarkers and potential therapeutic targets in children with CKD.

Your Work Environment

The VASC-OPATH project, funded by the French National Research Agency (ANR, JCJC 2026 call, "Translational health research" axis), is coordinated by Dr Julie Bernardor, paediatric nephrologist and Assistant Professor - Hospital Practitioner (MCU-PH). The PhD student will be co-supervised by Dr Julie Bernardor and Dr Stoyan Ivanov (immunologist, expert in myeloid cell biology), and will more broadly benefit from established collaborations with LP2M teams (immunology, iPSC models) as well as from the project's international clinical and scientific network (Prof. Claus Peter Schmitt, Heidelberg; UCA GenomiX and MICA platforms, Nice). The PhD student will be strongly involved in all aspects of the project (18 person-months for the coordinator and 36 person-months dedicated to the PhD student over the project duration), with cross-cutting involvement across the 3 work packages (snRNAseq, vascular organoids, CRISPR validation).

Constraints and risks

Work on human biological samples (paediatric arterioles, biobanked material), in strict compliance with ethical and regulatory requirements (Declaration of Helsinki, GDPR, ethics committees). Handling of iPSC lines genetically modified by CRISPR/Cas9. Occasional lone working may be required (experimental scheduling, core facilities).

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

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