Willem A. Dik, PhD

Dik51x53px Medical Immunologist,
 Laboratory Medical Immunology,
 Department of Immunology

 Email contact:  w.dik@erasmusmc.nl

 Immune Regulation Diagnostics (IRD) Research Group

The research in the group aims at the identification of cellular and molecular mechanisms underlying (chronic) inflammatory processes and related tissue remodeling and organ dysfunction, with the specific goal to use this information to guide the development of (novel) protective measures to be used in the clinic. There is a strong focus on ocular disease, including a.o. Graves ophthalmopathy, (autoimmune) uveitis, vitreoretinal disorders such as proliferative vitreoretinopahty (PVR), diabetic retinopathy (DR) and retinal toxicity due to treatment with the antimalarials chloroquine and hydroxychloroquine. The studies use various types of patient tissue and make extensive use of in vitro approaches (stimulation of for instance retinal pigment epithelial cells/retinal endothelial cells/orbital fibroblasts with ocular fluids, serum, plasma, or specific growth factors) as well as ex vivo approaches (tissue cultures in the presence and absence of specific drugs) to study mechanistic aspects of disease and to identify druggable targets and suitable drugs. The research is performed in a multi-disciplinary setting together with medical specialists and scientists from different (medical) fields, both national and international.

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To our diagnostic activities  

 Group members

Willem A. Dik, Group leader
Benjamin Schrijver, PhD student
Rina La Distia Nora, PhD student
Marja Smits-te Nijenhuis, Technician (Diagnostics)
Nicole Nagtzaam, Technician (Diagnostics)
Marion Kolijn-Cowenberg, Technician (Diagnostics)
Sandra Posthumus-van Sluijs, Technician (Diagnostics)
Angelique van Rijswijk, Technician (Diagnostics) 
Conny van Holten-Neelen, Technician (Research)
Pamela Vasic, Technician (Research)

 Selected Publications

(Check for all publications: Dik WA in Pubmed)

Dik WA, Virakul S, van Steensel L.
Current perspectives on the role of orbital fibroblasts in the pathogenesis of Graves’ophthalmopaty.
Exp Eye Res. 2015; in press.

Korthagen NM, van Bilsen K, Swagemakers SM, van de Peppel J, Bastiaans J, van der Spek PJ, van Hagen PM, Dik WA.
Retinal pigment epithelial cells display specific transcriptional responses upon TNF-α stimulation.
Br J Ophthalmol. 2015; in press (Epub Feb 13).

Bastiaans J, van Meurs JC, Mulder VC, Nagtzaam NM, Smits-te Nijenhuis M, Dufour-van den Goorbergh DC, van Hagen PM, Hooijkaas H, Dik WA.
The role of thrombin in proliverative vitreoretinopathy.
Invest Ophthalmol Vis Sci. 2014;55:4659-66.

Virakul S, Dalm VA, Paridaens D, van den Bosch WA, Hirankarn N, van Hagen PM, Dik WA.
The tyrosine kinase inhibitor dasatinib effectively blocks PDGF-induced orbital fibroblast activation.
Graefes Arch Clin Exp Ophthalmol. 2014;252:1101-9.

Bastiaans J, van Meurs JC, van Holten-Neelen C, Nagtzaam NM, van Hagen PM, Chambers RC, Hooijkaas H, Dik WA.
Thrombin induces epithelial-mesenchymal transition and collagen production by retinal pigment epithelial cells via autocrine PDGF-receptor signaling.
Invest Ophthalmol Vis Sci. 2013;54:8306-14.

van der Weerd K, van Hagen PM, Schrijver B, Kwekkeboom DJ, de Herder WW, ten Broek MR, Postema PT, van Dongen JJ, Staal FJ, Dik WA.
The peripheral blood compartment in patients with Graves’ disease: activated T-lymphocytes and increased transitional and pre-naive mature B-lymphocytes.
Clin Exp Immunol. 2013;174:256-64.

Bastiaans J, van Meurs JC, van Holten-Neelen C, Smits-te Nijenhuis M, Kolijn-Couwenberg MJ, van Hagen PM, Kuijpers RW, Hooijkaas H, Dik WA.
Factor Xa and thrombin stimulate proinflammatory and profibrotic mediator production by retinal pigment epithelial cells: a role in vitreoretinal disorders?
Graefes Arch Clin Exp Ophthalmol. 2013;251:1723-33.

Kamphuis LS, van Zelm MC, Lam KH, Rimmelzwaan GF, Baarsma GS, Dik WA, Thio HB, van Daele PL, van Velthoven ME, Batstra MR, van Hagen PM, van Laar JA.
Perigranuloma localization and abnormal maturation of B cells: emerging key players in sarcoidosis?
Am J Respir Crit Care Med. 2013;187:406-16.

van Steensel L, Hooijkaas H, Paridaens D, van den Bosch WA, Kuijpers RW, Drexhage HA van Hagen PM, Dik WA.
PDGF enhances orbital fibroblast responses to TSHR stimulating autoantibodies in Graves’ ophthalmopathy patients.
J Clin Endocrinol Metab. 2012;97:E944-53.

van Steensel L, Paridaens D, van Meurs M, van Hagen PM, van den Bosch WA, Kuijpers RW, Drexhage HA, Hooijkaas H, Dik WA.
Orbit infiltrating mast cells, monocytes, and macrophages produce PDGF isoforms that orchestrate orbital fibroblast activation in Graves’ ophthalmopathy.
J Clin Endocrinol Metab. 2012;97:E400-8.

van der Weerd K, Dik WA, Schrijver B, Schweitzer DH, Langerak AW, Drexhage HA, Kiewiet RM, van Aken MO, van Huisstede A, van Dongen JJ, van der Lelij AJ, Staal FJ, van Hagen PM.
Morbidly obese human subjects have increased peripheral blood CD4+ T cells with skewing toward a Treg-and Th2-dominated phenotype.
Diabetes. 2012;61:401-8.

Kamphuis LS, Lam-Tse WK, Dik WA, van Daele PL, van Biezen P, Kwekkeboom DJ, Kuijpers RW, Hooijkaas H, van Laar JA, Bastiaans J, Baarsma GS, van Hagen PM.
Efficacy of adalimumab in chronically active and symptomatic patients with sarcoidosis.
Am J Respir Crit Care Med. 2011;184:1214-6.

van der Zee HH, Laman JD, de Ruiter L, Dik WA, Prens EP.
Adalimumab (anti-tumor necrosis factor-α) treatment of hidradenitis suppuravita ameliorates skin inflammation: an in situ and ex vivo study.
Br J Dermatol. 2012;166:298-305.

van Bilsen K, van Hagen PM, Bastiaans J, van Meurs JC, Misotten T, Kuijpers RW, Hooijkaas H, Dingjan GM, Baarsma GS, Dik WA.
The neonatal Fc receptor is expressed by human retinal pigment epithelial cells and is downregulated by tumor necrosis factor-alpha.
Br J Ophthalmol. 2011;95:864-8.

van Steensel L, van Hagen PM, Paridaens D, Kuijpers RW, van den Bosch WA, Drexhage HA, Hooijkaas H, Dik WA.
Whole orbital tissue culture identifies imatinib mesylate and adalimumab as potential therapeutics for Graves’ ophthalmopathy.
Br J Ophthalmol. 2011;95:735-8.

van Steensel L, Paridaens D, Dingjan GM, van Daele PL, van Hagen PM, Kuijpers RW, van den Bosch WA, Drexhage HA, Hooijkaas H, Dik WA.
Platelet-derived growth factor-BB: a stimulus for cytokine production by orbital fibroblasts in Graves’ ophthalmopathy.
Invest Ophthalmol Vis Sci. 2010;51:1002-7.

van Steensel L, Paridaens D, Schrijver B, Dingjan GM, van Daele PL, van Hagen PM, van den Bosch WA, Drexhage HA, Hooijkaas H, Dik WA.
Imatinib mesylate and AMN107 inhibit PDGF-signaling in orbital fibroblasts: a potential treatment option for Graves’ ophthalmopathy.
Invest Ophthalmol Vis Sci. 2009;50: 3091-8.

van Daele PL, Dik WA, Thio HB, van Hal PT, van Laar JA, Hooijkaas H, van Hagen PM.
Is imatinib mesylate a promising drug in systemic sclerosis?
Arthritis Rheum. 2008;58:2549-52.