Full project description ESR 18

ESR 18Molecular imaging of angiogenesis and therapeutic effects of anti-angiogenetic agents in rheumatoid arthritis – POSITION FILLED

PhD research

Host:

Dr Conny J. van de Laken

Department of Rheumatology

Amsterdam UMC, location VUMC

Duration: 48 months

Background

Angiogenesis is present in synovial tissue of joints in RA patients from the very early stage onwards. Hereby, angiogenesis is a potential valuable target for early diagnosis of RA and monitoring of treatment efficacy. Endothelial cells (EC) are pivotal in the process of angiogenesis, as their activation can result in the formation of new blood vessels. Our group developed a number of anti-angiogenic agents that target and block EC activity and hereby angiogenesis.

In order to detect and monitor therapeutic effects on angiogenesis in inflamed joints, sensitive imaging techniques are required. Our group has previously shown that molecular imaging using Positron Emission Tomography (PET) and specific PET tracers is a highly sensitive and potentially specific imaging approach to visualize inflammatory activity in RA.

Our Hypothesis is that Angiogenesis in synovial tissue in RA can be targeted (1) to detect disease activity in RA, and (2) to monitor therapeutic effects of novel agents that intervene with angiogenesis.  This hypothesis will be investigated using novel molecular imaging tracers and pharmacological inhibitors.

Approach 

The workplan will consist of 2 phases:

1) Novel molecular imaging biomarkers that target angiogenesis will be generated and investigated in the project for their potential to detect inflammatory activity in preclinical (in vitro and in vivo) RA models.

2) Therapeutic monitoring of therapeutic blockade of angiogenesis in preclinical RA models using molecular imaging techniques.

The PhD candidate will coordinate and perform these studies, analyse the data and write scientific articles to report the results.  

Our research team

– Dept. of Rheumatology (location VUmc & AMC): Dr. C.J. vd Laken(associate professor and expert in translational molecular imaging of immunology) , dr. G. Jansen (biochemist and expert in areas of therapeutics and drug resistance) , prof. dr. R.F. v Vollenhoven (head of department and expert in large clinical trials in several reumatic diseases, such as rheumatoid arthritis and SLE), dr. S.W. Tas (associate professor and expert in angiogenesis in rheumatic diseases).

– Dept. of Medical Oncology (Cancer Center Amsterdam): Prof. dr. A. Griffioen (expert in angiogenesis in oncology)

– Dept. Radiology & Nuclear Medicine (AMC-location VUmc): dr. W. Beaino, dr. D. Vugts, prof. dr. A.D. Windhorst, prof.dr. G.A.M.S. van Dongen (expert team to perform translational molecular imaging studies in immunology).