A5010265948- Cancer-related Molecular Pathways
- Liver Disease Diagnosis and Treatment
- Epigenetics and DNA Methylation
- DNA Repair Mechanisms
- Ubiquitin and proteasome pathways
- Telomeres, Telomerase, and Senescence
- Microtubule and mitosis dynamics
- Liver physiology and pathology
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Diet and metabolism studies
- Cancer Cells and Metastasis
- Pancreatic function and diabetes
- Peroxisome Proliferator-Activated Receptors
- Cancer Genomics and Diagnostics
- Hepatitis B Virus Studies
- Drug Transport and Resistance Mechanisms
- Genomics and Chromatin Dynamics
- Mitochondrial Function and Pathology
- Genetics, Aging, and Longevity in Model Organisms
- Immune Cell Function and Interaction
- NF-κB Signaling Pathways
- Autoimmune Bullous Skin Diseases
- Adipose Tissue and Metabolism
- Cancer Research and Treatments
University Medical Center Groningen
2016-2025
University of Groningen
2016-2025
Utrecht University
2016-2025
University Medical Center Utrecht
2009-2023
Cancer Genetics (United States)
2003-2023
Dialyse Centrum Groningen
2023
U-M Rogel Cancer Center
2008-2023
Maastricht University
2019-2023
University of Teramo
2022
University of Veterinary Medicine
2013-2019
Cellular senescence suppresses cancer by irreversibly arresting cell proliferation. Senescent cells acquire a proinflammatory senescence-associated secretory phenotype. Many genotoxic chemotherapies target proliferating nonspecifically, often with adverse reactions. In accord prior work, we show that several chemotherapeutic drugs induce of primary murine and human cells. Using transgenic mouse permits tracking eliminating senescent cells, therapy-induced (TIS) persist contribute to local...
Abstract We developed stromal- and epithelial-specific cre-transgenic mice to directly visualize epithelial-mesenchymal transition (EMT) during cancer progression in vivo. Using three different oncogene-driven mouse mammary tumor models cell-fate mapping strategies, we show vivo evidence for the existence of EMT breast that myc can specifically elicit this process. Hierarchical cluster analysis genome-wide loss heterozygosity reveals incidence invasive human carcinomas is rare, but when it...
Rationale: Several studies have suggested a role for the gut microbiota in inflammation and atherogenesis. A causal relation relationship between microbiota, inflammation, atherosclerosis has not been explored previously. Objective: Here, we investigated whether proinflammatory from Caspase1 −/− ( Casp1 ) mice accelerates atherogenesis Ldlr mice. Method Results: We treated female with antibiotics subsequently transplanted them fecal based on cohousing approach. Autologous transplantation of...
Aging | doi:10.18632/aging.100738. Roel A van der Heijden, Fareeba Sheedfar, Martine C Morrison, Pascal PH Hommelberg, Danny Kor, Niels J Kloosterhuis, Nanda Gruben, Sameh Youssef, Alain de Bruin, Marten H Hofker, Robert Kleemann, Debby PY Koonen, Peter Heeringa
The mammalian E2F family of transcription factors plays a crucial role in the regulation cellular proliferation, apoptosis, and differentiation. Consistent with its biological number important processes, regulates expression genes involved cell cycle, DNA replication, repair, mitosis. It has proven difficult, however, to determine specific roles played by various known members these processes. work presented here now extends complexity this even further identification novel member, which we...
In pemphigus vulgaris (PV), autoantibody binding to desmoglein (Dsg) 3 induces loss of intercellular adhesion in skin and mucous membranes. Two hypotheses are currently favored explain the underlying molecular mechanisms: (a) disruption through steric hindrance, (b) interference desmosomal cadherin-bound antibody with intracellular events, which we speculated involve plakoglobin. To investigate second hypothesis established keratinocyte cultures from plakoglobin knockout (PG−/−) embryos...
The E2F transcription factor family plays a crucial and well established role in cell cycle progression. Deregulation of activities vivo leads to developmental defects cancer. Based on current evidence the field, mammalian E2Fs can be functionally categorized into either transcriptional activators (E2F1, E2F2, E2F3a) or repressors (E2F3b, E2F4, E2F5, E2F6, E2F7). We have identified novel member, E2F8, which is conserved mice humans has its counterpart Arabidopsis thaliana (E2Ls)....
E2F transcription factors are known to be important for timely activation of G 1 /S and 2 /M genes required cell cycle progression, but transcriptional mechanisms deactivation cycle-regulated unknown. Here, we show that E2F7 is highly expressed during mid late S-phase, occupies promoters /S-regulated represses their transcription. ChIP-seq analysis revealed binds preferentially genomic sites containing the TTCCCGCC motif, which closely resembles consensus site. We identified 89 target carry...
Disruption of the retinoblastoma (RB) tumor suppressor pathway, either through genetic mutation upstream regulatory components or RB1 itself, is believed to be a required event in cancer. However, alterations RB-regulated E2F family transcription factors are infrequent, casting doubt on direct role for E2Fs driving In this work, analysis human cancer revealed subtle but impactful copy number gains E2F1 and E2F3 hepatocellular carcinoma (HCC). Using series loss- gain-of-function alleles dial...
The recent development of 3D-liver stem cell cultures (hepatic organoids) opens up new avenues for gene and/or therapy to treat liver disease. To test safety and efficacy, a relevant large animal model is essential but not yet established. Because its shared pathologies disease pathways, the dog considered best human Here we report establishment long-term canine hepatic organoid culture allowing undifferentiated expansion progenitor cells that can be differentiated toward functional...
Abstract DNA damage has been implicated in ageing, but direct evidence for a causal relationship is lacking, owing to the difficulty of inducing defined lesions cells and tissues without simultaneously damaging other biomolecules cellular structures. Here we directly test whether highly toxic double-strand breaks (DSBs) alone can drive an ageing phenotype using adenovirus-based system based on tetracycline-controlled expression SacI restriction enzyme. We deliver adenovirus mice compare...
Aging | doi:10.18632/aging.100652. Fareeba Sheedfar, Miranda MY Sung, Marcela Aparicio-Vergara, Niels J Kloosterhuis, Maria Eugenia Miquilena-Colina, Javier Vargas-Castrillón, Febbraio, René L Jacobs, Alain de Bruin, Manlio Vinciguerra, Carmelo GarcÃa-Monzón, Marten H Hofker, Jason RB Dyck, Debby PY Koonen