A5043624517- Nanopore and Nanochannel Transport Studies
- Glioma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Advanced Neural Network Applications
- Genomics and Phylogenetic Studies
- Fuel Cells and Related Materials
- Extracellular vesicles in disease
- FOXO transcription factor regulation
- Genetic factors in colorectal cancer
- Vascular Malformations Diagnosis and Treatment
- Psoriasis: Treatment and Pathogenesis
- Cancer Cells and Metastasis
- Single-cell and spatial transcriptomics
- Cytokine Signaling Pathways and Interactions
- Retinoids in leukemia and cellular processes
- Domain Adaptation and Few-Shot Learning
- Circadian rhythm and melatonin
- Photoreceptor and optogenetics research
- Sulfur Compounds in Biology
- Genetics, Aging, and Longevity in Model Organisms
- Renal and related cancers
- Enhanced Oil Recovery Techniques
- Advanced Electron Microscopy Techniques and Applications
- S100 Proteins and Annexins
- Genomics and Chromatin Dynamics
University Medical Center Utrecht
2019-2025
Utrecht University
2019-2025
Oncode Institute
2020-2025
University of Arizona Cancer Center
2024
University Hospital Heidelberg
2019-2020
Heidelberg University
2019-2020
The Netherlands Cancer Institute
2020
Cancer Genomics Centre
2019
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...
Differential WNT and Notch signaling regulates differentiation of Lgr5+ crypt-based columnar cells (CBCs) into intestinal cell lineages. Recently we showed that mitochondrial activity supports CBCs, while adjacent Paneth (PCs) show reduced activity. This implies CBC PCs involves a metabolic transition toward downregulation dependency. Here Forkhead box O (FoxO) transcription factors interact in determining fate. In agreement with the organoid data, Foxo1/3/4 deletion mouse intestine induces...
Nanopore-based DNA sequencing relies on basecalling the electric current signal. Basecalling requires neural networks to achieve competitive accuracies. To improve accuracy further, new models are continuously proposed with architectures. However, benchmarking is currently not standardized, and evaluation metrics datasets used defined a per publication basis, impeding progress in field. This makes it impossible distinguish data from model driven improvements.
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....
Redox signaling is controlled by the reversible oxidation of cysteine thiols, a post-translational modification triggered H2O2 acting as second messenger. However, actually reacts poorly with most thiols and it not clear how discriminates between cysteines to trigger appropriate cascades in presence dedicated scavengers like peroxiredoxins (PRDXs). It was recently suggested that act peroxidases facilitate H2O2-dependent redox-regulated proteins via disulfide exchange reactions. unknown...
Shallow genome-wide cell-free DNA (cfDNA) sequencing holds great promise for non-invasive cancer monitoring by providing reliable copy number alteration (CNA) and fragmentomic profiles. Single nucleotide variations (SNVs) are, however, much harder to identify with low depth due errors. Here we present Nanopore Rolling Circle Amplification (RCA)-enhanced Consensus Sequencing (NanoRCS), which leverages RCA consensus calling based on long-read nanopore enable simultaneous multimodal tumor...
Abstract Besides genetic alterations, the cellular environment also determines disease onset and progression. When different cell types contribute to outcome, this imposes environmental challenges as likely differ in their extracellular dependencies. Hsa‐microRNA‐31‐5p (miR‐31) is highly expressed keratinocytes of psoriatic skin, we show that expression induced by limited glucose availability enables increased survival under limiting conditions increasing glutamine metabolism. In addition,...
Reversible cysteine oxidation plays an essential role in redox signaling by reversibly altering protein structure and function. Cysteine may lead to intra- intermolecular disulfide formation, the latter can drastically stabilize protein-protein interactions a more oxidizing milieu. The activity of tumor suppressor p53 is regulated at multiple levels, including various post-translational modification (PTM) interactions. In past few decades, has been shown be redox-sensitive protein, undergoes...
In eukaryotes, nucleosomes form a barrier to DNA templated reactions and must be dynamically disrupted provide access the genome. During nucleosome (re)assembly, histones can replaced by new histones, erasing post-translational modifications. Measuring histone turnover in mammalian cells has mostly relied on inducible overexpression of which may influence distort natural deposition rates. We have previously used recombination-induced tag exchange (RITE) study dynamics budding yeast. RITE is...
Summary Differential signalling of the WNT and Notch pathways regulates proliferation differentiation Lgr5 + crypt-based columnar cells (CBCs) into all cell lineages intestine. We have recently shown that high mitochondrial activity in CBCs is key maintaining stem function. Interestingly, while drives CBCs, it reduced adjacent secretory Paneth (PCs). This observation implies during towards PCs, undergo a metabolic rewiring involving downregulation number activity, through hitherto unknown...
Nanopore sequencing offers the ability for real-time analysis of long DNA sequences at a low cost, enabling new applications such as early detection cancer. Due to complex nature nanopore measurements and high cost obtaining ground truth datasets, there is need simulators. Existing simulators rely on handcrafted rules parameters do not learn an internal representation that would allow analysing underlying biological factors interest. Instead, we propose VADA, purely data-driven method...
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...
Shallow genome-wide cell-free DNA (cfDNA) sequencing holds great promise for non-invasive cancer monitoring by providing reliable copy number alteration (CNA) and fragmentomic profiles. Single nucleotide variations (SNVs) are, however, much harder to identify with low depth due errors. Here we present Nanopore Rolling Circle Amplification (RCA)-enhanced Consensus Sequencing (NanoRCS), which leverages RCA consensus calling based on long-read nanopore enable simultaneous multimodal tumor...
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 BACKGROUND Central nervous system (CNS) tumors are the most lethal category of tumors, particularly among children. Most commonly, first line treatment CNS is neurosurgical resection tumor. During this procedure a delicate balance must be struck between extent and risk comorbidity. Ideally, surgical plan based on detailed classification However often unknown at start surgery. Current practice consists preoperative imaging intraoperative diagnosis achieved by rapid histological...
A bstract Nanopore-based DNA sequencing relies on basecalling the electric current signal. Basecalling requires neural networks to achieve competitive accuracies. To improve accuracy further, new models are continuously proposed. However, benchmarking is currently not standardized, and evaluation metrics datasets used defined a per publication basis, impeding progress in field. standardize process of benchmarking, we unified existing rigorous set metrics. We benchmarked latest seven...
Differential signalling of the WNT and Notch pathways regulates proliferation differentiation Lgr5+ crypt-based columnar cells (CBCs) into all cell lineages intestine. We have recently shown that high mitochondrial activity in CBCs is key maintaining stem function. Interestingly, while drives CBCs, it reduced adjacent secretory Paneth (PCs). This observation implies during towards PCs, undergo a metabolic rewiring involving downregulation number activity, through hitherto unknown mechanism....
Abstract Psoriasis is characterized by a combination of keratinocyte hyperproliferation and immune cell activation. Immune activation requires increased glucose consumption, consequently limiting availability for other types like keratinocytes. In psoriasis Hsa-microRNA-31-5p (miR-31) highly expressed in Here we show that miR-31 expression keratinocytes induced limited increases survival under conditions, increasing glutamine metabolism. addition, metabolism results secretion specific...
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...