PhD candidate 'Treating kidney disease by targeting a novel pathway that protects the kidney filter from injury'
In this project, we aim to characterize the endothelium-to-podocyte NO-mediated paracrine GFB signaling pathway, and test the promise of therapeutically …
- Geert Grooteplein Zuid, Nijmegen, Gelderland
- Tijdelijk contract / Tijdelijke opdracht
- Uren per week:
- 36 - 36 uur
- € 2422 - € 3103 per maand
In this project, we aim to characterize the endothelium-to-podocyte NO-mediated paracrine GFB signaling pathway, and test the promise of therapeutically targeting this pathway by repurposing already available drugs. The project entails both in vitro model systems (including our glomerulus-on-a-chip model), as well as in vivo studies using specific kidney disease animal models as well as e.g. conditional podocyte-specific knockout animals.
Kidney diseases impact millions of people worldwide and can result in progressive chronic kidney disease (CKD), eventually necessitating renal replacement therapy through dialysis or kidney transplantation.
The glomerular filtration barrier (GFB) is a crucial part of the nephron, which is the functional unit of the kidney. GFB injury is a general characteristic of several kidney diseases and, if persistent, ultimately leads to loss of nephrons and kidney failure. Novel therapies to treat GFB injury or the ensuing progressive CKD have not emerged during the last decades. Thus, there is an unmet need for novel treatment targets in GFB injury, which can be translated into clinically applicable therapies at short term.
It is increasingly recognized that paracrine signaling between glomerular endothelial cells (GEnCs) and glomerular visceral epithelial cells (podocytes) is crucial to GFB integrity. We recently showed that nitric oxide (NO) produced by GEnCs can activate a podocyte signaling pathway crucial to maintain podocyte viability. Furthermore, GFB injury is associated with NO deficiency. This pathway can be therapeutically targeted by repurposing the class of sGC stimulator/activator drugs, mimicking the effect of NO on the podocyte.
Highlights of the current project:
- Innovative research question based on a recently discovered signaling cascade.
- Use of state-of-the-art in vitro (glomerulus-on-a-chip) and in vivo model systems.
- An excellent and ambitious research environment and team, including basic scientists and clinicians.
- Translation of basic research into novel therapeutic targets in kidney disease.
- Plan, perform, analyze, and discuss experiments.
- Contribute to scientific publications and present findings at scientific meetings.
- Work together in a team in a stimulating environment.
- Complete your project with a PhD thesis.
- Master in Molecular Life Sciences, Molecular Biology, Biochemistry, or similar.
- Experience in cell culture, molecular and cell biological techniques.
- Affinity and/or experience in performing animal experiments (Article 9 is preferable).
- Competencies we value: enthusiasm, humor, high working standards, independent, team player, well-structured, communicative, reliable, ambitious.
ConditionsUpon commencement of employment we require a certificate of conduct (Verklaring Omtrent het Gedrag, VOG) and there will be, depending on the type of job, a screening based on the provided cv. Radboud university medical center's HR Department will apply for this certificate on your behalf.
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Additional informationApplicants are requested to send a letter of application outlining their specific interest in the position and a curriculum vitae including 2 references.
All additional information about the vacancy can be obtained from the project leaders: Tom Nijenhuis, MD, PhD, internist-nephrologist, +31 (0)24 361 47 61 or Johan van der Vlag, PhD, Professor in Immunology of Kidney Diseases and Transplantation, +31 (0)24 361 65 39. Use the Apply button to submit your application.
Please apply before December 11, 2020.
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