A5066376879- Glioma Diagnosis and Treatment
- Brain Metastases and Treatment
- Genomics and Chromatin Dynamics
- Congenital gastrointestinal and neural anomalies
- Radiomics and Machine Learning in Medical Imaging
- Intestinal Malrotation and Obstruction Disorders
- RNA Research and Splicing
- RNA modifications and cancer
- Chromosomal and Genetic Variations
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Genomics and Phylogenetic Studies
- Congenital Anomalies and Fetal Surgery
- Genetic Associations and Epidemiology
- Prenatal Screening and Diagnostics
- Genetics and Neurodevelopmental Disorders
- Renal and related cancers
- Genomic variations and chromosomal abnormalities
- Ubiquitin and proteasome pathways
- Gene expression and cancer classification
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
Erasmus MC
2016-2025
Erasmus University Rotterdam
2014-2025
Medical University of Lublin
2022
Laboratory of Molecular Genetics
2022
Instytut Biologii Doświadczalnej im. Marcelego Nenckiego
2022
Polish Academy of Sciences
2022
Erasmus MC - Sophia Children’s Hospital
2022
Harokopio University of Athens
2022
Erasmus MC Cancer Institute
2018
Netherlands Bioinformatics Centre
2011-2015
Significance For the 2m DNA to fit into tiny cell nucleus, it is wrapped around nucleosomes and folded loops clustering together in domains. Genome function depends on this 3D-organization, especially on-going dynamic processes like transcription. Techniques studying network of contacts genome-wide have recently revealed 3D architecture, but protein factors behind are not understood. We study two proteins that known help form loops: cohesin CTCC-binding factor (CTCF). Respective depletion...
Pseudo-TORCH syndrome (PTS) is characterized by microcephaly, enlarged ventricles, cerebral calcification, and, occasionally, systemic features at birth resembling the sequelae of congenital infection but in absence an infectious agent. Genetic defects resulting activation type 1 interferon (IFN) responses have been documented to cause Aicardi-Goutières syndrome, which a PTS. Ubiquitin-specific peptidase 18 (USP18) key negative regulator I IFN signaling. In this study, we identified...
Significance Rare recessive monogenic diseases are often found in isolated populations. In one such population, we identified a child carrying homozygous nonsense mutation an understudied smooth muscle-restricted gene called Leiomodin1 ( LMOD1 ). Heterozygous parents showed no disease; however, the died shortly after birth from rare condition known as megacystis microcolon intestinal hypoperistalsis syndrome. A mouse model with similar Lmod1 mutation, engineered CRISPR-Cas9 genome editing,...
Noninvasive prenatal screening (NIPS) using cell-free DNA in maternal blood is highly sensitive for detecting fetal trisomies 21, 18, and 13. Using a genome-wide approach, other chromosome anomalies can also be detected. We report on the origin, frequency, clinical significance of these aberrations found pregnancies at risk trisomy or Whole-genome shallow massively parallel sequencing was used all autosomes were analyzed. In 78 2,527 cases (3.1%) NIPS indicative 13, 41 (1.6%) aberrations....
Abstract Purpose: In a post hoc analysis of the CATNON trial (NCT00626990), we explored whether adding temozolomide to radiotherapy improves outcome in patients with IDH1/2 wildtype (wt) anaplastic astrocytomas molecular features glioblastoma [redesignated as glioblastoma, isocitrate dehydrogenase–wildtype (IDH-wt) 2021 World Health Organization (WHO) classification central nervous system tumors]. Patients and Methods: From randomized phase III study examining addition adjuvant concurrent...
Significant efforts have recently been put into the investigation of spatial organization and chromatin-interaction networks genomes. Chromosome conformation capture (3C) technology its derivatives are important tools used in this effort. However, many these limitations, such as being limited to one viewpoint, expensive with moderate low resolution, and/or requiring a large sequencing Techniques like Hi-C provide genome-wide analysis. it requires massive effort considerable costs. Here we...
Hirschsprung disease (HSCR), which is congenital obstruction of the bowel, results from a failure enteric nervous system (ENS) progenitors to migrate, proliferate, differentiate, or survive within distal intestine. Previous studies that have searched for genes underlying HSCR focused on ENS-related pathways and not fitting current knowledge thus often been ignored. We identify validate novel using whole exome sequencing (WES), burden tests, in silico prediction, unbiased vivo analyses...
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in TSC1 and TSC2. Conventional DNA diagnostic screens identify a or TSC2 mutation 75 - 90% of individuals categorised with definite TSC. The remaining either have that undetectable using conventional methods, possibly another as yet unidentified gene. Here we apply targeted Next Generation Sequencing (NGS) approach to screen the complete genomic loci 7 fulfilling clinical criteria for TSC whom no were...
The NIPBL/MAU2 heterodimer loads cohesin onto chromatin. Mutations in NIPBL account for most cases of the rare developmental disorder Cornelia de Lange syndrome (CdLS). Here we report a MAU2 variant causing CdLS, deletion seven amino acids that impairs interaction between and N terminus. Investigating this interaction, discovered terminus are largely dispensable normal function cells with early truncating mutation. Despite predicted fatal outcome an out-of-frame single nucleotide duplication...
Survival in patients with IDH1/2-mutant (mt) anaplastic astrocytomas is highly variable. We have used the prospective phase 3 CATNON trial to identify molecular factors related outcome IDH1/2mt astrocytoma patients.The randomized 751 adult newly diagnosed 1p/19q non-codeleted glioma 59.4 Gy radiotherapy +/- concurrent and/or adjuvant temozolomide. The presence of necrosis microvascular proliferation was scored at central pathology review. Infinium MethylationEPIC BeadChip arrays were for...
Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (MMIHS) is a rare congenital disorder, in which heterozygous missense variants the Enteric Smooth Muscle actin γ-2 (ACTG2) gene have been recently identified. To investigate mechanism by ACTG2 lead to MMIHS, we screened cohort of eleven MMIHS patients, eight sporadic and three familial cases, performed immunohistochemistry, molecular modeling dynamics (MD) simulations, vitro assays. In all variant was expression detected intestinal...
Non-small cell lung carcinoma (NSCLC) is a complex malignancy that owing to its heterogeneity and poor prognosis poses many challenges diagnosis, patient treatment. DNA methylation an important mechanism of epigenetic regulation involved in normal development cancer. It very stable specific modification therefore principle suitable marker for phenotyping tumors. Here we present genome-wide analysis NSCLC samples paired tissues, where combine MethylCap next generation sequencing...
A deficiency in cystic fibrosis transmembrane conductance regulator (CFTR) function CF leads to chronic lung disease. is associated with abnormalities fatty acids, ceramides, and cholesterol, their relationship pathology not completely understood. Therefore, we examined the impact of CFTR on lipid metabolism pro-inflammatory signaling airway epithelium using mass spectrometric, protein array. We observed a striking imbalance acid ceramide metabolism, oxidative stress under basal conditions...
Evasion from drug-induced apoptosis is a crucial mechanism of cancer treatment resistance. The proapoptotic protein NOXA marks an aggressive pancreatic ductal adenocarcinoma (PDAC) subtype. To identify drugs that unleash the death-inducing potential NOXA, we performed unbiased drug screening experiment. In NOXA-deficient isogenic cellular models, identified inhibitor transcription factor heterodimer CBFβ/RUNX1. By genetic gain and loss function experiments, validated mode action depends on...
Memory T cells provide long-lasting defense responses through their ability to rapidly reactivate, but how they efficiently "recall" an inflammatory transcriptional program remains unclear. Here, we show that human CD4+ memory helper 2 (TH2) carry a chromatin landscape synergistically reprogrammed at both one-dimensional (1D) and 3D levels accommodate recall responses, which is absent in naive cells. In TH2 cells, genes were epigenetically primed the maintenance of transcription-permissive...