1) B cell autoimmunity: we study the cellular and molecular mechanisms operating in human autoreactive B cells, using mainly ACPA-positive B cells as model. In collaboration with Prof Hergen Spits, we cloned a large series of normal and autoreactive memory B cells from rheumatoid arthritis patients and healthy controls. We study key molecular switches in these cells, including mechanisms related to co-stimulation, germinal center formation, cytokine production, and B-T cell interactions. In collaboration with Dr Niek de Vries, we study the clonal expansion and repertoires of these autoreactive cells.
2) Cellular and molecular pathways of chronic tissue inflammation: using synovial inflammation in human spondyloarthritis as model, we study how key cytokine axis (in particular: TNF and IL-23/IL-17) operate in chronic tissue inflammation.
3) Animal models of spondyloarthritis: rheumatic diseases are not only characterized by chronic inflammation but also by pronounced structural damage to musculoskeletal organs. Spondyloarthritis is characterized by pathological new bone formation, which is very difficult to study in humans as this is a very slow process and access to tissue samples is difficult. Therefore, we set up animal models of SpA which allow us to mechanistaically study the interaction between inflammation and new bone formation and to preclinically test novel therapeutic strategies.
4) Novel therapies in spondyloarthritis: in this clinical part of our research program, we conduct phase II and IIIa clinical trials (both investigator-initiated and pharma-driven) with novel compounds in spondyloarthritis. Biological samples obtained in these trials are used for translational lab reserach (see 2). Moreover, we study biomarkers that can help us to select and stratify patient populations of appropriate treatment strategies.
5) Fc receptors as key determinants of myeloid cell-driven inflammation: this program is driven by a junior independent researcher, Jeroen den Dunnen (VENI and AMC Fellowship) and studies how different Fc receptors interact with TLRs to determine the myeloid immune response in infection and inflammation.
Theme: Infection and Immunity