A5005069677- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- CRISPR and Genetic Engineering
- Animal Genetics and Reproduction
- Cancer Research and Treatments
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Cancer Mechanisms and Therapy
- Axon Guidance and Neuronal Signaling
- Occupational and environmental lung diseases
- PI3K/AKT/mTOR signaling in cancer
- Monoclonal and Polyclonal Antibodies Research
- Cancer Cells and Metastasis
- Virus-based gene therapy research
- Pluripotent Stem Cells Research
- Cell Adhesion Molecules Research
- Peptidase Inhibition and Analysis
- Neurogenesis and neuroplasticity mechanisms
- Wnt/β-catenin signaling in development and cancer
- Telomeres, Telomerase, and Senescence
- Cellular Mechanics and Interactions
The Netherlands Cancer Institute
2014-2024
Oncode Institute
2001-2021
Cancer Genomics Centre
2001-2017
Delft University of Technology
2010
Wellcome Sanger Institute
2010
Albert Einstein College of Medicine
2010
National Hospital for Neurology and Neurosurgery
2002
University College London
2002
Pasteur Hellenic Institute
2000
Alexander Fleming Biomedical Sciences Research Center
2000
Low-grade inflammation is a hallmark of old age and central driver ageing-associated impairment disease1. Multiple factors can contribute to inflammation2; however, the molecular pathways that transduce aberrant inflammatory signalling their impact in natural ageing remain unclear. Here we show cGAS-STING pathway, which mediates immune sensing DNA3, critical chronic functional decline during ageing. Blockade STING suppresses phenotypes senescent human cells tissues, attenuates ageing-related...
Senescent renal epithelia promote fibrosis and functional loss after injury, whereas depletion improves regeneration in aged or irradiated kidneys.
Apolipoprotein (apo) E3-Leiden, described in a large Dutch family, is associated with dominantly inherited form of familial dysbetalipoproteinemia. To study the effect APOE*3-Leiden mutation vivo, transgenic mice were generated using genomic 27-kilobase DNA construct isolated from proband. This carried APOE gene, APOC1 and all known regulatory elements including an element that mediates liver expression. Three strains showed human All had significantly elevated levels total plasma...
PTEN is a tumour suppressor gene involved in cell cycle control, apoptosis and mediation of adhesion migration signalling. Germline mutations humans are associated with familial syndromes, among them Cowden disease. Glioblastomas, highly malignant glial tumours the central nervous system frequently show loss PTEN. Recent reports have outlined some aspects function development. Using conditional disruption approach, we inactivated Pten mice early during embryogenesis locally region specific...
Ligand-activated Cre recombinases are widely used for studying gene function in vitro and conditional mouse models. To compare ligand-dependent recombinases, different estrogen receptor fusions were introduced into the ROSA26 locus of embryonic stem (ES) cells assayed genotoxicity recombination efficiency. Of tested CreERT2 variant showed no toxicity was highly responsive to ligand induction. constitutively express mice also clarify whether system displays background activity, we generated a...
Abstract The PTEN tumor suppressor gene is frequently inactivated in human tumors, including prostate cancer. Based on the Cre/loxP system, we generated a novel mouse cancer model by targeted inactivation of Pten gene. In this model, Cre recombinase was expressed under control prostate-specific antigen (PSA) promoter. Conditional biallelic and monoallelic knock-out mice were viable recombination prostate-specific. Mouse cohorts systematically characterized at 4 to 5, 7 9, 10 14 months. A...
The transmembrane protein deleted in colorectal cancer (DCC) and its ligand, netrin-1, regulate synaptogenesis during development, but their function the mature central nervous system is unknown. Given that DCC promotes cell-cell adhesion, expressed by neurons, activates proteins signal at synapses, we hypothesized expression neurons regulates synaptic plasticity adult brain. We report enriched dendritic spines of pyramidal wild-type mice, demonstrate selective deletion from forebrain...
SUMMARY Breast cancer is the most common malignancy in women of Western world. Even though a large percentage breast patients show pathological complete remission after standard treatment regimes, approximately 30–40% are non-responsive and ultimately develop metastatic disease. To generate good preclinical model invasive cancer, we have taken tissue-specific approach to somatically inactivate p53 E-cadherin, cardinal cell-cell adhesion receptor that strongly associated with tumor...
Adolescence is a period of heightened susceptibility to psychiatric disorders medial prefrontal cortex (mPFC) dysfunction and cognitive impairment. mPFC dopamine (DA) projections reach maturity only in early adulthood, when their control over cognition becomes fully functional. The mechanisms governing this protracted unique development are unknown. Here we identify dcc as the first DA neuron gene regulate connectivity during adolescence dissect involved. Reduction or loss from neurons by...
Abstract Triacylglycerols (TAGs) are the main source of stored energy in body, providing an important substrate pool for mitochondrial beta-oxidation. Imbalances amount TAGs associated with obesity, cardiac disease and various other pathologies 1,2 . In humans, synthesized from excess, coenzyme A-conjugated fatty acids by diacylglycerol O -acyltransferases (DGAT1 DGAT2) 3 organisms, this activity is complemented additional enzymes 4 , but whether such alternative pathways exist humans...
The proto-oncogene bcl-3 is a member of the IkappaB family. Bcl-3 protein known to interact specifically with p50 and p52 subunits NFkappaB. However, function this interaction not well understood. To determine in vivo role Bcl-3, mice were generated that lack gene, Bcl 3(-/-). Here we report 3(-/-) appear developmentally normal, but exhibit severe defects humoral immune responses protection from pathogenic challenges. Relative wild-type mice, are unable clear L. monocytogenes more...
Vascular SMC proliferation is a crucial event in occlusive cardiovascular diseases. PPARα nuclear receptor controlling lipid metabolism and inflammation, but its role the regulation of growth remains to be established. Here, we show that controls cell-cycle progression at G1/S transition by targeting cyclin-dependent kinase inhibitor tumor suppressor p16INK4a (p16), resulting an inhibition retinoblastoma protein phosphorylation. activates p16 gene transcription both binding canonical...