Prof. PhD R.M. Luiten (Pigment cell disorders of the skin)
Luiten's research team is specialized in the immunopathogenesis and treatment of pigment cell disorders of the skin, including vitiligo and melanoma. Luiten's research has clearly established a positive relation between vitiligo and melanoma regression, by showing that 1) vitiligo patients have a three-fold decreased life-time risk of developing melanoma , 2) vitiligo is an autoimmunity against melanocytes in the skin, leading to loss of skin pigmentation, 3) melanoma patients who develop vitiligo, referred to as melanoma-associated leucoderma or vitiligo (MAL), have immunity reactive with both melanocytes and melanoma cells, 4) the appearance of MAL in melanoma patients is associated with favorable clinical outcome (progression free- and overall survival), and 5) vitiligo-inducing compound monobenzone combined with imiquimod and/or CpG induces anti-melanoma immunity and suppresses melanoma growth in mice and patients. This highlights vitiligo as a favorable sign for melanoma patients and the importance of its mechanism of action for melanoma treatment. The group has developed a new melanoma therapy consisting of monobenzone and immune stimulation (patent granted, preclinical and clinical proof-of-concept obtained). Their investigator-initiated clinical trial at the NKI-AVL shows local clinical responses of skin metastases and successful induction of anti-melanoma immunity in most patients. This therapy is developed further clinically. New projects include biomarker research for response of melanoma patients to immune checkpoint inhibitors, targeting of melanoma cell heterogeneity by vaccination immunotherapy and diagnosis and treatment of lentigo maligna. Vitiligo clinical research aims at improving skin suspension transplantation therapy and the development of scoring systems for vitiligo disease activity. Biomarkers for the differential diagnosis of vitiligo and melanoma-associated vitiligo are studied, applicable in preventing immunesuppressive therapy in vitiligo patients with an undiagnosed melanoma. Luiten's group joined forces of the NFU expertise center on Pigment Disorders (AMC) with the skin tissue engineering expertise of prof Gibbs (VUMC), to apply this technology in vitiligo and melanoma immunotherapy research.
PhD W. Ouwerkerk
BEng S. Chielie
BEng G. Krebbers
N.O.P. van Uden
Prof. PhD D.L.P. Baeten (Immunopathology of chronic inflammatory arthritis)
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
MSc M. Leeuw
T.F. van der Plas-Heijda
A.E.M. van Tillo-Klaver
M.N. van Tok
N.O.P. van Uden