A5003606943- Liver physiology and pathology
- Pancreatic function and diabetes
- Cancer Cells and Metastasis
- Hepatitis B Virus Studies
- Digestive system and related health
- Pancreatic and Hepatic Oncology Research
- Cellular transport and secretion
- 3D Printing in Biomedical Research
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Calcium signaling and nucleotide metabolism
- Epigenetics and DNA Methylation
- Renal and related cancers
- Clinical Nutrition and Gastroenterology
- Pediatric Hepatobiliary Diseases and Treatments
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Liver Disease Diagnosis and Treatment
- Pluripotent Stem Cells Research
- PI3K/AKT/mTOR signaling in cancer
- Genetic and Kidney Cyst Diseases
- Cancer-related gene regulation
- Cytokine Signaling Pathways and Interactions
- Mast cells and histamine
- CRISPR and Genetic Engineering
- Whipple's Disease and Interleukins
ETH Zurich
2010-2024
Royal Netherlands Academy of Arts and Sciences
2015-2022
Hubrecht Institute for Developmental Biology and Stem Cell Research
2016-2021
University Medical Center Utrecht
2016-2021
Utrecht University
2019-2020
Oncode Institute
2018-2020
Royal Academy of Art
2015-2018
Inserm
2012-2013
Centre National de la Recherche Scientifique
2012-2013
Université de Strasbourg
2012-2013
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...
The molecular events that drive hepatitis B virus (HBV)-mediated transformation and tumorigenesis have remained largely unclear, due to the absence of a relevant primary model system. Here we propose use human liver organoids as platform for modeling HBV infection related tumorigenesis. We first describe ex vivo HBV-infection derived from healthy donor after challenge with recombinant or HBV-infected patient serum. produced covalently closed circular DNA (cccDNA) early antigen (HBeAg),...
Article23 December 2019Open Access Transparent process NEDD4 and NEDD4L regulate Wnt signalling intestinal stem cell priming by degrading LGR5 receptor Laura Novellasdemunt Stem Cell Cancer Biology Laboratory, The Francis Crick Institute, London, UK Search for more papers this author Anna Kucharska Cara Jamieson Oncode Institute Department of Biology, Center Molecular Medicine, University Medical Utrecht, Netherlands Maria Prange-Barczynska Baulies Pedro Antas Jelte van der Vaart Hubrecht...
Abstract The development, homeostasis, and repair of intrahepatic extrahepatic bile ducts are thought to involve distinct mechanisms including proliferation maturation cholangiocyte progenitor cells. This study aimed characterize human organoids (ECO) using canonical Wnt-stimulated culture medium previously developed for (ICO). Paired ECO ICO were derived from common duct liver tissue, respectively. Characterization showed both organoid types highly similar, though some differences in size...
Despite their role in resolving inflammatory insults, neutrophils trigger inflammation-induced acute lung injury (ALI), culminating respiratory distress syndrome (ARDS), a frequent complication with high mortality humans. Molecular mechanisms underlying recruitment of to sites inflammation remain poorly understood. Here, we show that p38 MAP kinase p38δ is required for into sites. Global and myeloid-restricted deletion mice results decreased alveolar neutrophil accumulation attenuation ALI....
Hepatoblastoma is the most common childhood liver cancer. Although survival has improved significantly over past few decades, there remains a group of children with aggressive disease who do not respond to current treatment regimens. There critical need for novel models study hepatoblastoma as research find new treatments hampered by small number laboratory disease. Organoids have emerged robust many diseases, including We generated and characterized organoid model directly from freshly...
Abstract The DNA-PKcs inhibitor AZD7648 enhances CRISPR–Cas9-directed homology-directed repair efficiencies, with potential for clinical utility, but its possible on-target consequences are unknown. We found that genome editing causes frequent kilobase-scale and megabase-scale deletions, chromosome arm loss translocations. These large-scale chromosomal alterations evade detection through typical assays, prompting caution in deploying reinforcing the need to investigate multiple types of outcomes.
Abstract The rat is an important model for liver regeneration. However, there no in vitro culture system that can capture the massive proliferation be observed after partial hepatectomy rats. We here describe generation of stem cell lines. Rat cells, which grow as cystic organoids, were characterized by high expression marker Lgr5 , progenitor and duct markers low hepatocyte markers, oval stellate markers. Prolonged cultures organoids depended on levels WNT-signalling inhibition...
The shortage of liver organ donors is increasing and the need for viable alternatives urgent. Liver cell (hepatocyte) transplantation may be a less invasive treatment compared with transplantation. Unfortunately, hepatocytes cannot expanded in vitro, allogenic requires long-term immunosuppression. Organoid-derived adult stem cells can cultured indefinitely to create sufficient numbers transplantation, they are amenable gene correction. This study provides preclinical proof concept potential...
Fibrolamellar carcinoma (FLC) is a rare, often lethal, liver cancer affecting adolescents and young adults, for which there are no approved therapeutics. The development of therapeutics hampered by lack in vitro models. Organoids have shown utility as model system studying many diseases. In this study, tumor tissue the adjacent non-tumor were obtained at time surgery. was dissociated grown organoids. We developed 21 patient-derived organoid lines: 12 from metastases, three six liver. These...
Abstract The molecular events that drive Hepatitis B virus (HBV)-mediated transformation and tumorigenesis have remained largely unclear, due to the absence of a relevant primary model system. Here we propose use human liver organoids as platform for modeling HBV infection related tumorigenesis. We first describe ex vivo HBV-infection derived from healthy donor after challenge with recombinant or HBV-infected patient serum. infected produced cccDNA, expressed intracellular RNA proteins,...