A5037430089- Genomics and Chromatin Dynamics
- Glioma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Cancer Genomics and Diagnostics
- Chromosomal and Genetic Variations
- RNA Research and Splicing
- RNA modifications and cancer
- Extracellular vesicles in disease
- Single-cell and spatial transcriptomics
- Acute Myeloid Leukemia Research
- Plant Molecular Biology Research
- Neurogenetic and Muscular Disorders Research
- Acute Lymphoblastic Leukemia research
- Advanced biosensing and bioanalysis techniques
- Vascular Malformations Diagnosis and Treatment
- Cancer-related gene regulation
- Infectious Diseases and Mycology
- Chronic Myeloid Leukemia Treatments
- Brain Tumor Detection and Classification
- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Veterinary Equine Medical Research
- Antifungal resistance and susceptibility
- Animal health and immunology
- Meningioma and schwannoma management
University Medical Center Utrecht
2016-2025
Oncode Institute
2018-2025
Utrecht University
2015-2024
Hubrecht Institute for Developmental Biology and Stem Cell Research
2016-2023
Royal Netherlands Academy of Arts and Sciences
2021
Abstract Central nervous system tumours represent one of the most lethal cancer types, particularly among children 1 . Primary treatment includes neurosurgical resection tumour, in which a delicate balance must be struck between maximizing extent and minimizing risk neurological damage comorbidity 2,3 However, surgeons have limited knowledge precise tumour type prior to surgery. Current standard practice relies on preoperative imaging intraoperative histological analysis, but these are not...
Detailed genomic contact maps have revealed that chromosomes are structurally organized in megabase-sized topologically associated domains (TADs) encompass smaller subTADs. These segregate the nuclear space to form active and inactive compartments, but cause consequence of compartmentalization largely unknown. Here, we combined lacO/lacR binding platforms with allele-specific 4C technologies track their precise position three-dimensional genome upon recruitment NANOG, SUV39H1, or EZH2. We...
Abstract DNA methylation is important for establishing and maintaining cell identity genomic stability. This achieved by regulating the accessibility of regulatory transcriptional elements compaction subtelomeric, centromeric, other inactive regions. Carcinogenesis accompanied a global loss in methylation, which facilitates transformation cells. Cancer hypomethylation may also cause instability, example through interference with protective function telomeres centromeres. However,...
Despite recent progress in genome topology knowledge, the role of repeats, which make up majority mammalian genomes, remains elusive. Satellite repeats are highly abundant sequences that cluster around centromeres, attract pericentromeric heterochromatin, and aggregate into nuclear chromocenters. These landmark structures assumed to form a repressive compartment nucleus genes recruited for silencing. We have designed strategy genome-wide identification pericentromere-associated domains...
Abstract Genomic DNA is constantly subjected to oxidative damage, which thought be one of the major drivers cancer and age-dependent decline. The most prominent consequence modification guanine into 8-hydroxyguanine (8-oxo-dG), has important mutagenic potential plays a role in methylation-mediated gene regulation. Methods simultaneously detect quantify 8-oxo-dG within its genomic context have been lacking; mainly because these methods rely on indirect detection or are based hydrolysis DNA....
Abstract In immunocompromised pediatric patients, diagnosing invasive pulmonary aspergillosis (IPA) poses a significant challenge. Next-Generation Sequencing (NGS) shows promise for detecting fungal DNA but lacks standardization. This study aims to advance towards clinical evaluation of liquid biopsy NGS Aspergillus detection, through an wet-lab procedures and computational analysis. Our findings support using both CHM13v2.0 GRCh38.p14 in host-read mapping reduce false-positives. We...
The complex 2 Mb survival motor neuron (SMN) locus on chromosome 5q13, including the spinal muscular atrophy (SMA)-causing gene SMN1 and modifier SMN2, remains incompletely resolved due to numerous segmental duplications. Variation in SMN2 copy number, presumably influenced by conversion, affects disease severity, though number alone has insufficient prognostic value limited genotype–phenotype correlations. With advancements newborn screening SMN-targeted therapies, identifying genetic...
Monoallelic inactivation of CCCTC-binding factor (CTCF) in human cancer drives altered methylated genomic states, CTCF occupancy at promoter and enhancer regions, deregulated global gene expression. In patients with T cell acute lymphoblastic leukemia (T-ALL), we find that acquired monoallelic CTCF-inactivating events drive subtle local effects nearly half t(5; 14) (q35; q32.2) rearranged patients, especially when CTCF-binding sites are preserved between the BCL11B TLX3 oncogene. These...
Abstract The complex 2 Mb survival motor neuron (SMN) locus on chromosome 5q13, including the spinal muscular atrophy (SMA)-causing gene SMN1 and modifier SMN2 , remains incompletely resolved due to numerous segmental duplications. Variation in copy number, presumably influenced by conversion, affects disease severity, though number alone has insufficient prognostic value limited genotype-phenotype correlations. With advancements newborn screening SMN -targeted therapies, identifying genetic...
Abstract Oxford Nanopore Technology (ONT) based methylation sequencing is increasingly recognized for its rapid and accurate classification of brain tumors. A process that crucial optimal patient treatment. However, widespread clinical utility currently limited by the need fresh-frozen biopsies not standard-of-care formalin-fixed, paraffin-embedded (FFPE) samples. Our study explores impact FFPE on DNA presents a developed validated protocol ONT-based tumor classification. We present...
Abstract INTRODUCTION Central nervous system tumors still represent one of the most challenging fields to create curation in pediatric oncology. The primary treatment always starts with a neurosurgical intervention obtain tumor tissue for diagnosis. In cases this is maximal safe resection tumor. oncological prognostic value extent determined by precise molecular diagnosis and per-operative ultra-fast classification central provides neurosurgeon relevant information choosing right strategy....
Abstract BACKGROUND The introduction of tumour classification by analysis DNA methylation has changed the landscape paediatric neuro-oncology. With launch Oxford Nanopore sequencing, generation sequencing data is possible in real-time, including information on base-modifications. Diverse tools for tissue have been developed recently. While this an important step towards optimization surgical treatment, pre-operative knowledge entity would further facilitate planning. Therefore, we...
Abstract Background Sepsis is the leading cause of death in newborn foals. This study investigates whether cell-free DNA (cfDNA) sequencing can enhance bacterial pathogen detection foals with suspected sepsis and addresses existing knowledge gaps diagnostic challenges. Methods We developed a f oal cf for b acteria i dentification ( FBI ) workflow, integrating wetlab computational protocols to detect increased cfDNA abundance blood. Specifically, cfFBI focusses on enriching molecules...
Abstract The primary treatment of CNS tumors starts with a neurosurgical resection in order to obtain tumor tissue for diagnosis and reduce load mass effect. neurosurgeon has decide between radical versus more conservative strategy prevent surgical morbidity. prognostic impact varies types. However due lack pre-operative tissue-based diagnostics, limited knowledge the precise type is available at time surgery. Current standard practice includes preoperative imaging intraoperative...
ABSTRACT Chromatin folding is increasingly recognized as a regulator of genomic processes such gene activity. Chromosome conformation capture (3C) methods have been developed to unravel genome topology through the analysis pair-wise chromatin contacts and identified many genes regulatory sequences that, in populations cells, are engaged multiple DNA interactions. However, cannot discern whether occur simultaneously or competition on individual chromosome. We present novel 3C method,...
Chromatin folding is increasingly recognized as a regulator of genomic processes such gene activity. Chromosome conformation capture (3C) methods have been developed to unravel genome topology through the analysis pair-wise chromatin contacts and identified many genes regulatory sequences that, in populations cells, are engaged multiple DNA interactions. However, cannot discern whether occur simultaneously or competition on individual chromosome. We present novel 3C method, Multi-Contact 4C...
The primary treatment of CNS tumors starts with a neurosurgical resection in order to obtain tumor tissue for diagnosis and reduce load mass effect. neurosurgeon has decide between radical versus more conservative strategy prevent surgical morbidity. prognostic impact varies types. However due lack pre-operative tissue-based diagnostics, limited knowledge the precise type is available at time surgery. Current standard practice includes preoperative imaging intraoperative histological...
Abstract BACKGROUND Preoperative imaging and intraoperative histological analysis provide important guidance during CNS tumor surgery but are not always precise enough. Also, the diagnosis of tumors increasingly requires a combination morphological molecular analysis. Illumina DNA methylation array provides information on hundreds thousands sites genome-wide is relatively time-consuming expensive. Nanopore sequencing enables real-time generation an profile. AIM: To exploit potential nanopore...