A5025320398- DNA Repair Mechanisms
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
- T-cell and B-cell Immunology
- Atherosclerosis and Cardiovascular Diseases
- Cancer, Hypoxia, and Metabolism
- Lipoproteins and Cardiovascular Health
- Immune Cell Function and Interaction
- Acute Lymphoblastic Leukemia research
- Acute Myeloid Leukemia Research
- Phagocytosis and Immune Regulation
- Pluripotent Stem Cells Research
- Cancer-related Molecular Pathways
- PARP inhibition in cancer therapy
- Chronic Myeloid Leukemia Treatments
- Carcinogens and Genotoxicity Assessment
- CAR-T cell therapy research
- Diabetes Treatment and Management
- Molecular Biology Techniques and Applications
- Genetic factors in colorectal cancer
- Antiplatelet Therapy and Cardiovascular Diseases
- Epigenetics and DNA Methylation
- Biomedical Ethics and Regulation
- Reproductive Biology and Fertility
AstraZeneca (United Kingdom)
2024
University of Amsterdam
2015-2020
Amsterdam UMC Location University of Amsterdam
2015-2020
Amsterdam University Medical Centers
2019-2020
Resverlogix (Canada)
2018-2020
Leiden University
2013
Elevated lipoprotein(a) [Lp(a)] is strongly associated with an increased cardiovascular disease (CVD) risk. We previously reported that pro-inflammatory activation of circulating monocytes a potential mechanism by which Lp(a) mediates CVD. Since potent Lp(a)-lowering therapies are emerging, it interest whether patients elevated experience beneficial anti-inflammatory effects following large reductions in Lp(a).Using transcriptome analysis, we show healthy individuals Lp(a), as well CVD...
Abstract Background Patients with cardiovascular disease (CVD) and type 2 diabetes (DM2) have a high residual risk for experiencing major adverse cardiac event. Dysregulation of epigenetic mechanisms gene transcription in innate immune cells contributes to CVD development but is currently not targeted by therapies. Apabetalone (RVX-208) small molecule inhibitor bromodomain extra-terminal (BET) proteins—histone acetylation readers that drive pro-inflammatory pro-atherosclerotic transcription....
Genotoxic stress induces Wnt signaling that attenuates apoptosis in embryonic stem cells.
Abstract The recombination activating gene (RAG) 1 and RAG2 protein complex introduces DNA breaks at Tcr Ig segments that are required for V(D)J in developing lymphocytes. Proper regulation of RAG1/2 expression safeguards the ordered assembly Ag receptors development lymphocytes, while minimizing risk collateral damage. ataxia telangiectasia mutated (ATM) kinase is involved repair RAG1/2-mediated prevents their propagation. simultaneous occurrence RAG1/2-dependent -independent lymphocytes...
The BCR-ABL1 fusion gene is the driver oncogene in chronic myeloid leukemia (CML) and Philadelphia-chromosome positive (Ph+) acute lymphoblastic (ALL). introduction of tyrosine kinase inhibitors (TKIs) targeting ABL (such as imatinib) has dramatically improved survival CML Ph+ ALL patients. However, primary acquired resistance to TKIs remains a clinical challenge. patients who achieve complete cytogenetic (CCR) or deep molecular response (MR) (≥4.5log reduction transcripts) represent...
ABSTRACT In B cells, the error-prone repair of activation-induced cytidine deaminase (AID)-induced lesions in immunoglobulin variable genes cause somatic hypermutation (SHM) antibody genes. Due to clonal selection germinal centers (GC) this active mutation process provides molecular basis for affinity maturation. AID deaminates cytosine (C) create uracil (U) DNA. Typically, short patch base excision (spBER) effectively restores genomic U lesions. We here demonstrate that GC cells actively...
The DNA damage response orchestrates the repair of lesions that occur spontaneously, are caused by genotoxic stress, or appear in context programmed breaks lymphocytes. Ataxia-Telangiectasia Mutated kinase (ATM), ATM- and Rad3-Related (ATR) catalytic subunit DNA-dependent Protein Kinase (DNA-PKcs) among first activated upon induction damage, central regulators a network controls repair, apoptosis cell survival. As part tumor-suppressive pathway, ATM ATR activate p53 through phosphorylation,...
Introduction: Hyperactivation of the monocyte inflammatory response is partly controlled by epigenetic mechanisms and contributes to atherosclerotic plaque formation in patients with cardiovascular disease (CVD) type 2 diabetes mellitus (DM2). Hypothesis: Monocyte activation DM2+CVD regulated bromodomain extraterminal (BET) readers can be inhibited apabetalone - a clinical stage BET inhibitor. Methods: CD14+ monocytes from 14 12 matched control subjects were treated ex vivo 25 μM ± U/mL...