A5001702841- Protein Degradation and Inhibitors
- Acute Lymphoblastic Leukemia research
- Histone Deacetylase Inhibitors Research
- Chromatin Remodeling and Cancer
- Acute Myeloid Leukemia Research
- Parkinson's Disease Mechanisms and Treatments
- Cancer Immunotherapy and Biomarkers
- Nuclear Receptors and Signaling
- interferon and immune responses
- RNA modifications and cancer
- Chronic Myeloid Leukemia Treatments
- Retinoids in leukemia and cellular processes
- RNA Research and Splicing
- Autophagy in Disease and Therapy
- Autoimmune and Inflammatory Disorders Research
- Barrier Structure and Function Studies
- NF-κB Signaling Pathways
- Cancer therapeutics and mechanisms
- Lung Cancer Research Studies
- Cancer Mechanisms and Therapy
- Immunodeficiency and Autoimmune Disorders
- Immune Cell Function and Interaction
- Cellular transport and secretion
- Epigenetics and DNA Methylation
- Multiple Myeloma Research and Treatments
Amsterdam University Medical Centers
2023-2024
Amsterdam University of Applied Sciences
2023-2024
Amsterdam UMC Location Vrije Universiteit Amsterdam
2021
Cancer Center Amsterdam
2021
University of Bergen
2019-2021
Haukeland University Hospital
2019-2021
National Institutes of Health
2020
National Center for Advancing Translational Sciences
2020
National University Cancer Institute, Singapore
2015-2019
National University of Singapore
2014-2019
Somatic mutations in the spliceosome gene ZRSR2-located on X chromosome-are associated with myelodysplastic syndrome (MDS). ZRSR2 is involved recognition of 3'-splice site during early stages assembly; however, its precise role RNA splicing has remained unclear. Here we characterize as an essential component minor (U12 dependent) assembly. shRNA-mediated knockdown leads to impaired U12-type introns and RNA-sequencing MDS bone marrow reveals that loss activity causes increased mis-splicing....
Acute promyelocytic leukemia (APL) is a subtype of myeloid characterized by differentiation block at the promyelocyte stage. Besides presence chromosomal rearrangement t(15;17), leading to formation PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis primary and relapse APL identify somatic alterations, which cooperate with pathogenesis We explored landscape...
Abstract Background Parkinson’s disease (PD) is a complex, age-related neurodegenerative disorder of largely unknown etiology. PD strongly associated with mitochondrial respiratory dysfunction, which can lead to epigenetic dysregulation and specifically altered histone acetylation. Nevertheless, despite the emerging role epigenetics in brain disorders, question whether aberrant acetylation involved remains unresolved. Methods We studied fresh-frozen tissue from two independent cohorts...
<h2>Summary</h2> Transcytosis across the blood-brain barrier (BBB) regulates key processes of brain, but intracellular sorting mechanisms that determine successful receptor-mediated transcytosis in brain endothelial cells (BECs) remain unidentified. Here, we used Transferrin receptor-based Brain Shuttle constructs to investigate transport BECs, and uncovered a pathway for regulation transcytosis. By combining live-cell imaging mathematical modeling <i>in vitro</i> with super-resolution...
Precise regulation of chromatin architecture is vital to physiological processes including hematopoiesis. ARID1A a core component the mammalian SWI/SNF complex, which one ATP-dependent remodeling complexes. To uncover role in hematopoietic development, we utilized cell-specific deletion Arid1a mice. We demonstrate that essential for maintaining frequency and function stem cells its loss impairs differentiation both myeloid lymphoid lineages. deficiency led global reduction open ensuing...
Summary Background Therapeutic drug monitoring (TDM) has the potential to improve efficacy and diminish side effects. Measuring methotrexate‐polyglutamate (MTX‐PG) in erythrocytes might enable TDM for methotrexate patients with Crohn's disease (CD). Aim To investigate relationship between MTX‐PGs survival, toxicity Methods In a multicentre prospective cohort study, CD starting subcutaneous without biologics were included followed 12 months. Primary outcome was discontinuation or requirement...
CARD11 is a lymphocyte-specific scaffold molecule required for proper T/B cell activation in response to antigen. Germline gain-of-function (GOF) mutations the gene cause unique B lymphoproliferative disorder known as Expansion with NF-κB and T Anergy (BENTA). In contrast, patients carrying loss-of-function (LOF), dominant negative (DN) present severe atopic disease. Interestingly, both GOF DN variants primary immunodeficiency, recurrent bacterial viral infections, likely resulting from...
Chromosomal translocation t(8;21)(q22;q22) which leads to the generation of oncogenic RUNX1-RUNX1T1 (AML1-ETO) fusion is observed in approximately 10% acute myelogenous leukemia (AML). To identify somatic mutations that co-operate with t(8;21)-driven leukemia, we performed whole and targeted exome sequencing an Asian cohort at diagnosis relapse. We identified high frequency truncating alterations ASXL2 along recurrent KIT, TET2, MGA, FLT3, DHX15 this subtype AML. investigate depth role...
Intracellular methotrexate polyglutamates (MTX-PGs) concentrations are measurable in red blood cells (RBCs) during MTX treatment. MTX-PG
Small molecule based targeted therapies for the treatment of metastatic melanoma hold promise but responses are often not durable, and tumors frequently relapse. Response to adoptive cell transfer (ACT)-based immunotherapy in patients durable develop resistance primarily due loss antigen expression. The combination small molecules that sustain T effector function with ACT could lead long lasting responses. Here, we have developed a novel co-culture cell-based high throughput assay system...
Abstract Parkinson disease (PD) is a complex neurodegenerative disorder of largely unknown etiology. While several genetic risk factors have been identified, the involvement epigenetics in pathophysiology PD mostly unaccounted for. We conducted histone acetylome-wide association study PD, using brain tissue from two independent cohorts cases and controls. Immunoblotting revealed increased acetylation at sites with most prominent change observed for H3K27, marker active promoters enhancers....