A5049654634- Cytokine Signaling Pathways and Interactions
- Rheumatoid Arthritis Research and Therapies
- HER2/EGFR in Cancer Research
- Angiogenesis and VEGF in Cancer
- Blood Coagulation and Thrombosis Mechanisms
- NF-κB Signaling Pathways
- Atherosclerosis and Cardiovascular Diseases
- Inflammatory mediators and NSAID effects
- Cell Adhesion Molecules Research
- Venous Thromboembolism Diagnosis and Management
- Chemokine receptors and signaling
- Systemic Lupus Erythematosus Research
- Immune Response and Inflammation
- Platelet Disorders and Treatments
- Esophageal Cancer Research and Treatment
- Protease and Inhibitor Mechanisms
- Gastric Cancer Management and Outcomes
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Biomarkers in Disease Mechanisms
- Medicinal Plant Pharmacodynamics Research
- Lipoproteins and Cardiovascular Health
- Blood disorders and treatments
- Genetic Associations and Epidemiology
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- IL-33, ST2, and ILC Pathways
Leiden University Medical Center
2018-2021
Amsterdam UMC Location University of Amsterdam
2014-2019
University of Amsterdam
2014-2019
Amsterdam University Medical Centers
2019
Leiden University
2018
Marac (Greece)
2018
Center for Rheumatology
2016
Angiogenesis is essential during development and in pathological conditions such as chronic inflammation cancer progression. Inhibition of angiogenesis by targeting vascular endothelial growth factor (VEGF) blocks disease progression, but most patients eventually develop resistance which may result from compensatory signalling pathways. In cells (ECs), expression the pro-angiogenic chemokine CXCL12 regulated non-canonical nuclear (NF)-κB signalling. Here, we report that NF-κB-inducing kinase...
Angiogenesis is crucial in RA disease progression. Lymphotoxin β receptor (LTβR)-induced activation of the non-canonical nuclear factor-κB (NF-κB) pathway via NF-κB-inducing kinase (NIK) has been implicated this process. Consequently, inhibition may hold therapeutic potential RA. We describe a novel three-dimensional (3D) model synovial angiogenesis incorporating endothelial cells (ECs), fibroblast-like synoviocytes (RAFLSs) and fluid (RASF) to further investigate contributions NF-κB...
NF-κB-inducing kinase (NIK; also known as MAP3K14) is a central regulator of non-canonical NF-κB signaling in response to stimulation TNF receptor superfamily members, such the lymphotoxin-β (LTβR), and implicated pathological angiogenesis associated with chronic inflammation cancer. Here, we identify previously unrecognized role LTβR-NIK axis during inflammatory activation human endothelial cells (ECs). Engagement LTβR-triggered canonical promoted expression mediators adhesion molecules,...
Neovascularization is associated with atherosclerotic plaque instability and increased chance of myocardial infarction (MI). Patients chronic inflammatory diseases (CID) have risk atherosclerosis, evidence demonstrates that NF-κB inducing kinase (NIK)-mediated noncanonical signaling in endothelial cells (EC) linked to inflammation angiogenesis. Here, we hypothesized NIK may also be activated EC lesion microvessels.Using cohorts lesions from coronary carotid arteries, quantified expression...
Genome wide association studies (GWAS) identified SLC44A2 as a novel susceptibility gene for venous thrombosis (VT) and previous work established that contributed to clot formation upon vascular injury.To further investigate the role of in VT by utilizing deficient mice (Slc44a2-/- ) two representative disease models.Mice were included hypercoagulability model driven siRNA-mediated hepatic silencing anticoagulants Serpinc1 (antithrombin) Proc (protein C) flow restriction (stenosis) induced...
Abstract The plasma compartment of the blood holds important information on risk to develop cardiovascular diseases such as venous thrombosis (VT). Mass spectrometry-based targeted proteomics with internal standards quantifies proteins in multiplex allowing generation signatures associated a disease or condition. Here, demonstrate method, we investigate protein mice following onset VT, which was induced by RNA interference targeting natural anticoagulants antithrombin and C. We then study...
Anti‐angiogenic agents combined with chemotherapy is an important strategy for the treatment of solid tumors. However, survival benefit limited, urging improvement combination therapies. We aimed to clarify effects vascular endothelial growth factor receptor 2 (VEGFR2) targeting on hemodynamic function and penetration drugs in esophagogastric adenocarcinoma (EAC). Patient‐derived xenograft (PDX) models EAC were subjected long‐term short‐term anti‐VEGFR2 therapy followed by injection or...
Angiogenesis is essential for colorectal cancer (CRC) progression, as demonstrated by the beneficial clinical effects of therapeutics inhibiting VEGF signaling. However, alternative mechanisms neovascularization can develop, resulting in treatment failure. Previously we NF-κB-inducing kinase (NIK) contributes to pathological angiogenesis. Here, investigate NIK a therapeutic target endothelial cells (EC) CRC. To determine expression levels CRC tissues, immunostained both primary tumors and...
Background/Objective: Recent genome wide association studies identified SLC44A2 as a novel susceptibility locus for venous thromboembolism (VTE), region encoding the solute carrier family 44 member 2 protein (SLC44A2). Here we utilize Slc44a2 deficient mice (KO) to determine importance of in thrombotic disease. Methods: Mice lacking were included two models thrombosis: 1) spontaneous thrombosis model using siRNA targeting anti-coagulants Serpinc1 and Proc 2) deep vein (DVT) induced by flow...
<h3>Background</h3> Patients with chronic inflammatory diseases (CID) have higher risk of developing cardiovascular disease which may be in part due to increased systemic burden. In atherosclerosis, extensive neovascularization is associated plaque instability and chance myocardial infarction (MI). We established that non-canonical NF-κB signaling, its central regulator inducing kinase (NIK) endothelial cells (EC) contributes angiogenesis synovial tissue patients various types arthritis....
<h3>Background</h3> Angiogenesis is a crucial mediator in rheumatoid arthritis (RA) pathogenesis and blocking this process thought to have therapeutic potential ameliorating the disease. Current <i>in vitro</i> models of angiogenesis focus solely on endothelial cells (EC), however, RA fibroblast like synoviocytes (FLS), as well angiogenic mediators synovial fluid (SF), are also important contributors process. Therefore, model including both EC, FLS, SF would be more representative...
<h3>Background</h3> Angiogenesis contributes to rheumatoid arthritis (RA) pathogenesis, however, many models focus solely on endothelial cells (EC). We developed a 3D-spheroid model including both EC and RA fibroblast-like-synoviocytes (FLS) study angiogenesis associated with test the efficacy of several inhibitors targeting this process. Previous work demonstrated role for non-canonical NF-κB pathway its main regulator, NF-kB inducing kinase (NIK), in pathological thus we aim use 3D further...
<h3>Background</h3> Sites of chronic inflammation, such as rheumatoid arthritis (RA) synovial tissue, are characterised by neovascularization and often contain tertiary lymphoid structures with characteristic features organs high endothelial venules (HEV), sometimes even true germinal centres. Ligation the lymphotoxin (LT)-β receptor (LTβR) results in activation both canonical NF-κB-Inducing Kinase (NIK)-dependent noncanonical NF-κB signalling cells (EC) plays a crucial role neogenesis....
Atherothrombosis is the cause of death over 14 million people per year worldwide and murine models to replicate this process in vivo are mostly lacking. Previously we demonstrated that silencing anticoagulant protein C using RNA interference ( siProc ) induces spontaneous atherothrombosis aortic root apolipoprotein E-deficient Apoe -/- mice, albeit at a low incidence rate. Here aim determine if plaque susceptibility for rupture can be linked characteristics and/or blood composition,...