Academisch Medisch Centrum Universiteit van Amsterdam

Professor Paul-Peter Tak, MD, PhD, is director of the Division of Clinical Immunology and Rheumatology at the AMC. He has extensive experience in translational research. Prof. Tak received his medical degree cum laude from the Free University of Amsterdam, was board certified in Internal Medicine and Rheumatology and worked as a scientist at the Leiden University Medical Center where he received his PhD. In addition, he conducted research as a visiting scientist for two years at UCSD School of Medicine, La Jolla, California. Prof. Tak has extensive experience in phase I/II clinical trials and is a leading scientist in the field of experimental rheumatology. He is author of over 150 scientific publications and has various patents and pending patents.

The Division of Clinical Immunology and Rheumatology is part of the Department of Internal medicine (CIR) at the Academic Medical Center (AMC) in Amsterdam. The research of the CIR is focused on the research line “the pathogenesis of rheumatoid arthritis (RA) and development of innovative therapies” which encompasses a multidisciplinary approach to get more insight into the inflammatory processes that are involved in various stages of RA, psoriatic arthritis (PsA), and Sjögren’s disease and to translate this knowledge into novel therapeutic approaches for treating RA. Among the connective tissue diseases RA is the commonest and the most important in socio-economic terms. RA is a progressive destructive disorder that targets primarily the joints. Despite these high costs, inflammatory rheumatic disorders have often been neglected in favour of the immediate life threatening diseases. However, up to 3% of the European population suffers from inflammatory joint diseases which in many cases starts early in life. If osteoarthritis is included, this would be 10% of the population.  RA is associated with a high degree of economic loss, morbidity, and early mortality. RA patients who require hospital care have at least a twofold increased mortality when compared to normal individuals, and more severe RA is associated with higher mortality rates. The excess mortality in severe RA has been compared to that seen in three-vessel coronary artery disease or stage IV Hodgkin's disease.

Within the department research is performed at three different tiers:

Clinical studies: The aim of these studies is to evaluate new experimental therapies using biologicals. Currently phase I/II studies targeting chemokines, proinflammatory cytokines and B-cells are in progress. Using arthroscopy synovial tissue biopsies can be obtained from patients treated with the new therapeutics. The changes in synovial biopsy samples are used as biomarkers to predict possible clinical efficacy and to provide insight in the mechanism of action of the therapy. Material obtained from well-defined patients groups is also used in the Synoviomics project, which aims at identifying genes and proteins involved in the pathogenesis of various arthritides using microarray technology.

Animal studies: In parallel to work in human studies, experiments in animal models of arthritis are performed. These animal models are a feasible tool for studying the complex interplay of inflammation and joint destruction during arthritis and the effect of different therapies hereon.

In vitro studies: Fibroblast-like synoviocytes (FLS) isolated from patients with RA and related disorders are of particular interest as they are highly activated and exhibit certain features of transformed cells. Furthermore, synovial fluid and peripheral blood from patients is used to perform in vitro experiments, providing more insight into mechanisms involved in the pathogenesis of RA which are of great help interpreting results from the complex in vivo experiments.    

The major research interest is focused in the following areas:

- Pathogenetic studies on synovial inflammation in RA, PsA, and reactive arthritis (Funded by the Dutch Arthritis Association and NWO)
- Development and evaluation of immunotherapies in RA and PsA (Funded by NWO, ZON-MW, the Dutch Arthritis Association, and several pharmaceutical industries)
- Development of local gene therapy for RA (Funded by a NATO-science fellowship, the Dutch Arthritis Association, and biotech companies)
- Signal transduction pathways in rheumatoid arthritis (Funded by the Dutch Arthritis Association and biotech companies)

General information can be obtained at: p.p.tak@amc.uva.nl (division head) and k.a.reedquist@amc.uva.nl (primary investigator).

Information about specific research teams within our division can be found via the following links:

Clinical Trial Unit (Dr. Daan Gerlag, d.m.gerlag@amc.uva.nl)
Apoptosis Group (Dr. Philip Remans, p.h.remans@amc.uva.nl)
Dendritic Cell Group (Dr. Cristina Lebre, m.lebre@amc.uva.nl)
Gene Therapy Group (Dr. Margriet Vervoordeldonk, m.j.vervoordeldonk@amc.uva.nl)
Genetics Group (Dr. Niek de Vries, niek.devries@amc.uva.nl)
Signal Transduction Group (Dr. Kris Reedquist, k.a.reedquist@amc.uva.nl)
Spondylarthropathy Group (Dr. Dominique Baeten, d.l.baeten@amc.uva.nl)
Synovial Tissue and Digital Image Analysis Group (Dr. Tom Smeets, t.j.smeets@amc.uva.nl)