A5016282606- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Cancer Genomics and Diagnostics
- Genomics and Phylogenetic Studies
- Genomic variations and chromosomal abnormalities
- Cancer Immunotherapy and Biomarkers
- Genomics and Rare Diseases
- Chromosomal and Genetic Variations
- Cancer-related molecular mechanisms research
- Genetic factors in colorectal cancer
- MicroRNA in disease regulation
- Colorectal Cancer Treatments and Studies
- DNA Repair Mechanisms
- RNA modifications and cancer
- Molecular Biology Techniques and Applications
- Genomics and Chromatin Dynamics
- Ovarian cancer diagnosis and treatment
- Circular RNAs in diseases
- RNA Interference and Gene Delivery
- vaccines and immunoinformatics approaches
- Hepatocellular Carcinoma Treatment and Prognosis
- DNA and Nucleic Acid Chemistry
- RNA Research and Splicing
- Nanopore and Nanochannel Transport Studies
- CRISPR and Genetic Engineering
University Medical Center Utrecht
2015-2024
Utrecht University
2015-2023
Oncode Institute
2019-2022
Public Citizen
2022
Cancer Genomics Centre
2016-2021
University Hospital Heidelberg
2018-2020
Heidelberg University
2018-2020
University Medical Center
2019
Zero to Three
2018
ORCID
2018
MicroRNAs (miRNAs) are small noncoding RNAs, about 21 nucleotides in length, that can regulate gene expression by base-pairing to partially complementary mRNAs. Regulation miRNAs play essential roles embryonic development. We determined the temporal and spatial patterns of 115 conserved vertebrate zebrafish embryos microarrays situ hybridizations, using locked-nucleic acid–modified oligonucleotide probes. Most were expressed a highly tissue-specific manner during segmentation later stages,...
Several vertebrate microRNAs (miRNAs) have been implicated in cellular processes such as muscle differentiation, synapse function, and insulin secretion. In addition, analysis of Dicer null mutants has shown that miRNAs play a role tissue morphogenesis. Nonetheless, only few loss-of-function phenotypes for individual described to date. Here, we introduce quick versatile method interfere with miRNA function during zebrafish embryonic development. Morpholino oligonucleotides targeting the...
Abstract Background MicroRNA (miRNA) encoding genes are abundant in vertebrate genomes but very few have been studied any detail. Bioinformatic tools allow prediction of miRNA targets and this information coupled with knowledge expression profiles facilitates formulation hypotheses function. Although the central nervous system (CNS) is a prominent site expression, virtually nothing known about spatial temporal miRNAs brain. To provide an overview breadth CNS, we performed comprehensive...
Despite improvements in genomics technology, the detection of structural variants (SVs) from short-read sequencing still poses challenges, particularly for complex variation. Here we analyse genomes two patients with congenital abnormalities using MinION nanopore sequencer and a novel computational pipeline-NanoSV. We demonstrate that long reads are superior to short regard de novo chromothripsis rearrangements. The also enable efficient phasing genetic variations, which leveraged determine...
A variety of mutational mechanisms shape the dynamic architecture human genomes and occasionally result in congenital defects disease. Here, we used genome-wide long mate-pair sequencing to systematically screen for inherited de novo structural variation a trio including child with severe abnormalities. We identified 4321 variants 17 rearrangements. characterized changes base-pair level revealing complex series balanced inter- intra-chromosomal rearrangements consisting 12 breakpoints...
Abstract Aneuploidy is a hallmark of cancer and underlies genetic disorders characterized by severe developmental defects, yet the molecular mechanisms explaining its effects on cellular physiology remain elusive. Here we show, using series human cells with defined aneuploid karyotypes, that gain single chromosome increases genomic instability. Next-generation sequencing SNP-array analysis reveal accumulation chromosomal rearrangements in aneuploids, break point junction patterns suggestive...
MicroRNAs (miRNAs) are involved in the regulation of gene expression at post-transcriptional level by base pairing to 3'-UTR (untranslated region) mRNAs. The let-7 miRNA was first discovered Caenorhabditis elegans and is evolutionarily conserved. We used zebrafish embryos as a vertebrate vivo system study substrate requirements for function let-7. Injection double-stranded into zygotes frogs causes specific phenotypic defects. Only antisense strand duplex has biological activity. In...
There remains an unmet need for preclinical models to enable personalized therapy ovarian cancer (OC) patients. Here we evaluate the capacity of patient-derived organoids (PDOs) predict clinical drug response and functional consequences tumor heterogeneity. We included 36 whole-genome-characterized PDOs from 23 OC patients with known histories. maintain genomic features original lesion recapitulate patient neoadjuvant carboplatin/paclitaxel combination treatment. display inter- intrapatient...
Background: Although BRCA1-deficient tumors are extremely sensitive to DNA-damaging drugs and poly(ADP-ribose) polymerase (PARP) inhibitors, recurrences do occur and, consequently, resistance therapy remains a serious clinical problem. To study the underlying mechanisms, we induced in patient-derived xenograft (PDX) models of BRCA1-mutated BRCA1-methylated triple-negative breast cancer. Methods: A cohort 75 mice carrying PDX was treated with cisplatin, melphalan, nimustine, or olaparib,...
Structural variation (SV) influences genome organization and contributes to human disease. However, the complete mutational spectrum of SV has not been routinely captured in disease association studies. We sequenced 689 participants with autism disorder (ASD) other developmental abnormalities construct a genome-wide map large SV. Using long-insert jumping libraries at 105X mean physical coverage linked-read whole-genome sequencing from 10X Genomics, we document seven major classes ~5 kb...
Current normalization methods for RNA-sequencing data allow either intersample comparison to identify differentially expressed (DE) genes or intrasample the discovery and validation of gene signatures. Most studies on optimization typically use simulated validate methodologies. We describe a new method, GeTMM, which allows both inter- analyses with same normalized set. used actual (i.e. not simulated) RNA-seq from 263 colon cancers (no biological replicates) read count compare GeTMM most...
microRNAs (miRNAs) are small (~22 nucleotide) regulatory RNAs which play fundamental roles in many biological processes. Recent studies have shown that the expression of miRNAs is altered various human tumors and some may function as oncogenes or tumor suppressor genes. However, with exception glioblastoma multiforme, brain unknown. Furthermore, methods to profile from formalin-fixed, paraffin-embedded (FFPE) archival tissues study their cellular subcellular localization FFPE been lacking....
MicroRNAs (miRNAs) attenuate gene expression by means of translational inhibition and mRNA degradation. They are abundant, highly conserved, predicted to regulate a large number transcripts. Several hundred miRNA classes known, many associated with cell proliferation differentiation. Many exhibit tissue-specific expression, which aids in evaluating their functions, it has been assumed that high level sequence conservation implies conservation. A limited amount data supports this, although...
MicroRNAs (miRNAs) are involved in the regulation of gene expression at post-transcriptional level by base pairing to 3′-UTR (untranslated region) mRNAs. The let-7 miRNA was first discovered Caenorhabditis elegans and is evolutionarily conserved. We used zebrafish embryos as a vertebrate vivo system study substrate requirements for function let-7. Injection double-stranded into zygotes frogs causes specific phenotypic defects. Only antisense strand duplex has biological activity. In...
Structural rearrangements form a major class of somatic variation in cancer genomes. Local chromosome shattering, termed chromothripsis, is mechanism proposed to be the cause clustered chromosomal and was recently described occur small percentage tumors. The significance these clusters for tumor development or metastatic spread largely unclear.We used genome-wide long mate-pair sequencing SNP array profiling reveal that chromothripsis widespread phenomenon primary colorectal metastases. We...