Ruben van Boxtel
A5019020568- Cancer Genomics and Diagnostics
- Acute Myeloid Leukemia Research
- Acute Lymphoblastic Leukemia research
- CRISPR and Genetic Engineering
- Cancer Research and Treatments
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- Renal and related cancers
- Genetic factors in colorectal cancer
- Single-cell and spatial transcriptomics
- Pluripotent Stem Cells Research
- DNA Repair Mechanisms
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- DNA and Nucleic Acid Chemistry
- Immune Cell Function and Interaction
- Genomics and Chromatin Dynamics
- Pancreatic and Hepatic Oncology Research
- CAR-T cell therapy research
- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Hemoglobinopathies and Related Disorders
- Sarcoma Diagnosis and Treatment
- Genomics and Rare Diseases
- Liver physiology and pathology
- Animal Genetics and Reproduction
Princess Máxima Center
2018-2025
University Medical Center Utrecht
2011-2024
Oncode Institute
2017-2024
Palo Alto University
2024
Stanford University
2024
Utrecht University
2015-2019
Heidelberg University
2013-2019
University Hospital Heidelberg
2013-2019
Royal Netherlands Academy of Arts and Sciences
2010-2019
Hubrecht Institute for Developmental Biology and Stem Cell Research
2008-2018
Despite the enormous replication potential of human liver, there are currently no culture systems available that sustain hepatocyte and/or function in vitro. We have shown previously single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids vitro and differentiated into functional hepatocytes vivo. now describe conditions allowing long-term expansion adult bile duct-derived bipotent progenitor from liver. The highly stable at chromosome structural level, while base changes...
Base substitution catalogues represent historical records of mutational processes that have been active in a cell. Such can be distinguished by various characteristics, like mutation type, sequence context, transcriptional and replicative strand bias, genomic distribution association with (epi)-genomic features. We created MutationalPatterns, an R/Bioconductor package allows researchers to characterize broad range patterns base dissect the underlying molecular mechanisms. Furthermore, it...
A signature event for organoids Human cancer genomes harbor cryptic mutational signatures that represent the cumulative effects of DNA damage and defects in repair processes. Knowledge how specific originate could have a major impact on diagnosis prevention. One approach to address this question is reproduce experimental systems by genetic engineering then match those found naturally occurring cancers. Drost et al. used CRISPR-Cas9 delete certain enzymes from human colon organoids. In...
Previous studies have described that tumor organoids can capture the diversity of defined human carcinoma types. Here, we describe conditions for long-term culture mucosal organoids. Using this protocol, a panel 31 head and neck squamous cell (HNSCC)-derived organoid lines was established. This recapitulates genetic molecular characteristics previously HNSCC. Organoids retain their tumorigenic potential upon xenotransplantation. We observe differential responses to drugs including cisplatin,...
Abstract Most known pathogenic point mutations in humans are C•G to T•A substitutions, which can be directly repaired by adenine base editors (ABEs). In this study, we investigated the efficacy and safety of ABEs livers mice cynomolgus macaques for reduction blood low-density lipoprotein (LDL) levels. Lipid nanoparticle–based delivery mRNA encoding an ABE a single-guide RNA targeting PCSK9 , negative regulator LDL, induced up 67% editing (on average, 61%) 34% 26%) macaques. Plasma LDL levels...
Abstract Kidney tumours are among the most common solid in children, comprising distinct subtypes differing many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing disease heterogeneity currently lacking. Here, we describe first paediatric cancer organoid biobank. It contains tumour matching normal kidney organoids from over 50 children with different of cancer, Wilms tumours, malignant rhabdoid renal carcinomas, congenital mesoblastic nephromas....
Significance Metastasis is the main cause of cancer death, but underlying mechanisms are largely unknown. Here, we developed an orthotopic organoid transplantation approach and used engineered human colon tumor organoids to study contribution common CRC mutations metastasis. Using this approach, show that combination oncogenic in Wnt, EGFR, P53, TGF-β signaling pathways facilitates efficient cell migration These allow growth independent stem niche factors, enabling cells grow at foreign...
Mutation accumulation during life can contribute to hematopoietic dysfunction; however, the underlying dynamics are unknown. Somatic mutations in blood progenitors provide insight into rate and processes this accumulation, as well developmental lineage tree stem cell division numbers. Here, we catalog genomes of human-bone-marrow-derived umbilical-cord-blood-derived progenitor cells (HSPCs). We find that accumulate gradually with approximately 14 base substitutions per year. The majority...
Abstract Prime editing is a recent genome technology using fusion proteins of Cas9-nickase and reverse transcriptase, that holds promise to correct the vast majority genetic defects. Here, we develop prime for primary adult stem cells grown in organoid culture models. First, generate precise in-frame deletions gene encoding β‐catenin ( CTNNB1 ) result proliferation independent Wnt-stimuli, mimicking mechanism development liver cancer. Moreover, functionally recovers disease-causing mutations...
The collective of somatic mutations in a genome represents record mutational processes that have been operative cell. These can be investigated by extracting relevant patterns from sequencing data.