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:
Tasks and responsibilities:
- 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.