A5075871423- Cancer Genomics and Diagnostics
- Genomics and Rare Diseases
- Blood properties and coagulation
- BRCA gene mutations in cancer
- Breast Cancer Treatment Studies
- Gene expression and cancer classification
- Genetic factors in colorectal cancer
- HER2/EGFR in Cancer Research
- COVID-19 Clinical Research Studies
- 3D Printing in Biomedical Research
- Nutrition, Genetics, and Disease
- Collagen: Extraction and Characterization
- Cellular Mechanics and Interactions
- Genomic variations and chromosomal abnormalities
- Diagnosis and Treatment of Venous Diseases
- Genetics, Bioinformatics, and Biomedical Research
- Platelet Disorders and Treatments
- Molecular Biology Techniques and Applications
- Biomedical Text Mining and Ontologies
- Protease and Inhibitor Mechanisms
- Advanced Breast Cancer Therapies
- Rheology and Fluid Dynamics Studies
- Single-cell and spatial transcriptomics
- Nitric Oxide and Endothelin Effects
- Helicobacter pylori-related gastroenterology studies
Erasmus University Rotterdam
2025
Erasmus MC
2025
University Medical Center Utrecht
2022
Color (United States)
2017-2020
Agendia (Netherlands)
2012-2020
University of Amsterdam
2008-2012
European Organisation for Research and Treatment of Cancer
2012
Champalimaud Foundation
2012
UC Davis Comprehensive Cancer Center
2012
Institut Català d'Oncologia
2012
Recent advancements in next-generation sequencing have greatly expanded the use of multi-gene panel testing for hereditary cancer risk. Although genetic helps guide clinical diagnosis and management, recommendations are based on personal family history ethnicity, many carriers being missed. Herein, we report results from 23,179 individuals who were referred 30-gene risk, independent current guidelines-38.7% would not met National Comprehensive Cancer Network criteria testing. We identified a...
Many women with an elevated risk of hereditary breast and ovarian cancer have previously tested negative for pathogenic mutations in BRCA1 BRCA2. Among them, a subset has susceptibility to requires further testing. We sought identify specific groups who remain at high evaluate whether they should be offered multi-gene panel 300 on were enrolled long-term study UCSF. As part their care, all BRCA2 either by limited or comprehensive sequencing. Additionally, met one the following criteria: (i)...
While inward remodeling of small arteries in response to low blood flow, hypertension, and chronic vasoconstriction depends on type 2 transglutaminase (TG2), the mechanisms action have remained unresolved. We studied regulation TG2 activity, its (sub) cellular localization, substrates, specific mode during artery remodeling. found that isolated mouse mesenteric by exogenous required presence a reducing agent. The effect depended cross-linking as indicated lack mutant TG2. cell-permeable...
Advances in genome sequencing have led to a tremendous increase the discovery of novel missense variants, but evidence for determining clinical significance can be limited or conflicting. Here, we present Learning from Evidence Assess Pathogenicity (LEAP), machine learning model that utilizes variety feature categories classify and achieves high performance multiple genes different health conditions. Feature include functional predictions, splice population frequencies, conservation scores,...
Thrombotic complications are common in Coronavirus disease 2019 (COVID-19) patients, with pulmonary embolism (PE) being the most frequent. Randomised trials have provided inconclusive results on optimal dosage of thromboprophylaxis critically ill COVID-19 patients. We utilized data from multicentre CAPACITY-COVID patient registry to assess effect differential application Low Molecular Weight Heparin (LMWH) dose protocols PE and in-hospital mortality risk An instrumental variable analysis was...
Transglutaminase 2 (TG2) is a pleiotropic enzyme involved in both intra- and extracellular processes. In the matrix, TG2 stabilizes matrix by covalent cross-linking disulfide isomerase activity. These functions become especially apparent during remodeling as seen wound healing, tumor development vascular remodeling. However, lacks signal sequence for classical secretory mechanism, cellular mechanism of secretion currently unknown. We developed green fluorescent fusion protein to study...
Next generation sequencing (NGS) has become a common technology for clinical genetic tests. The quality of NGS calls varies widely and is influenced by features like reference sequence characteristics, read depth, mapping accuracy. With recent advances in software tools, the majority variants called using alone are fact accurate reliable. However, small subset difficult-to-call that still do require orthogonal confirmation exist. For this reason, many laboratories confirm results...
Thrombosis is a frequent and severe complication in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Lupus anticoagulant (LA) strong acquired risk factor for thrombosis various diseases frequently observed COVID-19. Whether LA associated COVID-19 currently unclear.To investigate if critically ill COVID-19.The presence of other antiphospholipid antibodies was assessed ICU. determined dilute Russell's viper venom time (dRVVT) LA-sensitive activated...
While matrix remodeling plays a key role in vascular physiology and pathology, the underlying mechanisms have remained incompletely understood. We studied of collagen matrices by individual smooth muscle cells (SMCs), clusters monolayers. In addition, we focused on contribution transglutaminase 2 (TG2), which an important small arteries. Single SMCs displaced fibers at distances up to least 300 μm course 8-12 h. This process involved both 'hauling up' local compaction distance from cells,...
Gene expression data obtained in large studies hold great promises for discovering disease signatures or subtypes through analysis. It is also prone to technical variation, whose removal essential avoid spurious discoveries. Because this variation not always known and can be confounded with biological signals, its a challenging task. Here we provide step-wise procedure comprehensive analysis of the MINDACT microarray dataset. The trial enrolled 6693 breast cancer patients prospectively...
384 Background: Between 25 and 35% of stage II colon cancer patients will experience a relapse their disease may benefit from adjuvant chemotherapy. ColoPrint is gene expression classifier that can predict in with early-stage colorectal (Salazar et al. JCO 2011). Methods: was developed using data whole genome microarrays validated in-silico datasets independent patient cohorts 5 European hospitals. Fresh frozen tissues, clinical parameters, MSI-status follow-up for were available. Samples...
Abstract Background Biology has become the main driver of breast cancer (BC) therapy. Biological subtypes have been recommended as a guide for treatment selection. Molecularly identified can be determined by gene expression profiling. Alternatively, pathology used to define surrogates these subtypes. These methodologies are not always concordant, which lead different systemic therapies. The purpose this preplanned translational research is investigate concordance between molecular based...
The relevance of large copy number variants (CNVs) to hereditary disorders has been long recognized, and population sequencing efforts have chronicled many common structural (SVs). However, limited data are available on the clinical contribution rare germline SVs. Here, a detailed characterization SVs identified using targeted next-generation was performed. Across 50 genes associated with cancer cardiovascular disorders, minimum 828 unique were reported, including 584 fully characterized...
1022 Background: Biology has become the main driver of breast cancer therapy. Intrinsic biological subtypes by gene expression profiling have been identified. Pathology can be used to define surrogates these but are not always concordant, which may lead different treatment plans. We investigated concordance between BluePrint (BP) + MammaPrint (MP) (micro array based) and pathological (based on ER, PR, HER2, Ki67). Contrary Perou set (evolved into PAM50), was trained using data. Methods:...
Microvascular remodeling is known to depend on cellular interactions with matrix tissue. However, it difficult study the role of specific cells or elements in an vivo setting. The aim this develop automated technique that can be employed obtain and analyze local collagen by single smooth muscle cells. We combined a motorized microscopic setup time-lapse video microscopy new cross-correlation based image analysis algorithm enable recording cell-induced reorganization. This method rendered...
Abstract Background: Biology has become the main driver of breast cancer therapy. Intrinsic biological subtypes by gene expression profiling have been identified. Pathology can be used to define surrogates these but are not always concordant, which may lead different treatment plans. We investigated concordance between BluePrint and MammaPrint (microarray-based) pathological (based on ER, PR, HER2 & Ki67). Methods: Using available data (centrally assessed pathology genomics) from MINDACT...
Inward remodeling of small arteries in response to low blood flow and hypertension depends on type 2 transglutaminase (TG2). We studied the regulation TG2 activity, its localization substrates during remodeling. Isolated mouse mesenteric exposed exogenous required a reducing agent induce inward The effect depended cross-linking as indicated by lack mutant TG2. cell-impermeable TCEP did not However, cell-permeable DTT induced translocation endogenous activity at smooth muscle membrane. This...
Transglutaminase 2 (TG2) is known to be important for both cross‐linking of matrix proteins as well cell adhesion, cytoskeletal organization and signaling. However, its cellular distribution mechanisms secretion activation during remodeling remain unclear. We tagged TG2 at the C‐terminal with eGFP. TG2/eGFP was transfected into HEK/293T cells using Effectene. Western blot in vitro activity assay showed a >100‐fold increase active TG2. No difference observed between non‐fluorescent...