Osteoarthritis (OA) is the most prevalent and debilitating joint disease worldwide with no curative treatment. Classically considered as a simple degenerative wear and tear disease, in recent years it has been perceived that both local and systemic inflammation are important for the disease process. OA is clearly linked to atherosclerosis and metabolic syndrome characterized by high cholesterol levels, largely transported in low density lipoprotein (LDL-c) particles. In this project we aim to unravel mechanisms involved in high LDL-c driven joint pathology during inflammatory osteoarthritis.

The PhD candidate will investigate mechanisms involved in the interplay between high cholesterol levels, the immune system and joint destruction in osteoarthritis (OA). Low grade joint inflammation is present in more than 50% of OA patients and recently it was found that high LDL-c levels contribute to macrophage activation within the synovium which coincided with development of joint destruction. Recently PCSK9 has been emerged as a new promising key therapeutic target for hypercholesteremia. PCSK9 is a protease that upon binding to the low density lipoprotein receptor (LDLR) causes its internalization and subsequent degradation which leads to strongly elevated LDL-c levels. Inhibition of PCSK9 maintains LDLR expression and strongly lowers LDL-c levels.

The goal of this project which is subsidized by the Dutch Arthritis Foundation is to unravel mechanisms involved in synovial activation and joint pathology in osteoarthritis and to investigate PCSK9 as a  novel therapeutic target to combat this crippling disease.

We offer an interesting temporary research position in a dynamic, multidisciplinary and international environment. The work will mainly be performed in the department of Rheumatology in Nijmegen.

• A university degree (MSc or equivalent) in biology with an interest in immunology, pathology and molecular biology;
• Experience with histology, culturing techniques and animal work (article 9) is recommended; 
• Excellent communication skills in spoken and written English;
• Capable of working independently as well as in a multi-disciplinary team;
• You recognise yourself in the Radboud way of working.

Fixed-term contract: 3 year with a possible extension to 4 year.

• Salary is € 2.279 gross per month in the first year up to a maximum of € 2.919 gross per month in the last fourth year, plus additional vacation bonus (8% per year) and end of year payments (8.3% per year)
• Upon commencement of employment we require a certificate of conduct (Verklaring Omtrent het Gedrag, VOG). Radboud university medical center’s HR Department will apply for this certificate on your behalf

Radboudumc (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 film.

Our key strength is medical life-sciences and clinical practice, with an impressive infrastructure comprising state-of-the-art technology platforms and (translational) research facilities. The Radboudumc is therefore uniquely positioned in the emerging Euregio and Dutch healthcare infrastructure to play a leading role in the new healthcare paradigm of prediction, prevention and personalised medicine.

The Radboudumc focuses on scientific health challenges of today, with an eye on emerging diseases of the future.

Read more about what it means to work at Radboudumc and how you can do your part.

https://www.radboudumc.nl/EN/Pages/default.aspx

A major focus of the department of Rheumatology, a EULAR centre of excellence, at the Radboud University Medical Centre in Nijmegen, is to gain better insight in the pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA). Our department contributed significantly (track record of more than 600 publications) to a better understanding of the inflammatory cascade and joint destruction in experimental models of arthritis/osteoarthritis. The research-group of Experimental Rheumatology in Nijmegen has gained a worldwide reputation in basic and clinical rheumatology research. The department takes part in the research program of the Nijmegen Radboud Institute for Molecular Life Sciences (RIMLS). The RIMLS trains students and PhD-students and conducts research in medical research.