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 (e.g. cell cultures and glomerulus-on-a-chip), 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:
CONDITIONS OF EMPLOYMENT
Fixed-term contract: 4 years.
Upon 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.
The Radboud university medical center (Radboudumc) is a top knowledge center with a strong emphasis on fundamental and translational research. The Department of Nephrology conducts fundamental / translational and clinical research into kidney disease and renal replacement therapies. Fundamental / translational research is aimed at unraveling the molecular and immunological mechanisms underlying glomerular disease and transplant rejection, and is performed in the Nephrology Research Laboratory, part of the Radboudumc Institute for Molecular Life Science (RIMLS), a leading research institute within the domain of molecular mechanisms of disease.
At the moment there are more than 1,300 PhD candidates at our medical hospital. This number includes PhD candidates on our pay roll as well as external candidates (those employed somewhere else but researching on our premises).
Read what it is like to do a PhD at the Radboud University Medical Center.
Radboudumc strives to be a leading developer of sustainable, innovative and affordable healthcare to improve the health and wellbeing of people and society in the Netherlands and beyond. This is the core of our mission: To have a significant impact on healthcare. To get a better picture of what this entails, check out our strategy.
Applicants 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 Dr. Tom Nijenhuis, internist-nephrologist, +31 (0)24 361 47 61 or Prof. Dr. Johan van der Vlag, 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 4 September 2020.
Recruitment agencies are asked not to respond to this job posting.