A5065618452- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- Cellular Mechanics and Interactions
- Pancreatic function and diabetes
- 3D Printing in Biomedical Research
- Single-cell and spatial transcriptomics
- Mathematical Biology Tumor Growth
- Pancreatic and Hepatic Oncology Research
- Breast Cancer Treatment Studies
- AI in cancer detection
- Estrogen and related hormone effects
- Nutrition, Genetics, and Disease
- Cell Image Analysis Techniques
- Photoacoustic and Ultrasonic Imaging
- Cancer, Stress, Anesthesia, and Immune Response
- Science, Research, and Medicine
- Cell Adhesion Molecules Research
- Planarian Biology and Electrostimulation
- Computational Drug Discovery Methods
- HER2/EGFR in Cancer Research
- Cellular transport and secretion
- Laser Applications in Dentistry and Medicine
- Radiomics and Machine Learning in Medical Imaging
- Renal and related cancers
- Brain Metastases and Treatment
Oncode Institute
2020-2025
The Netherlands Cancer Institute
2020-2025
Vrije Universiteit Brussel
2023
The Francis Crick Institute
2016-2021
The cell of origin pancreatic ductal adenocarcinoma (PDAC) has been controversial. Here, we show that identical oncogenic drivers trigger PDAC originating from both and acinar cells with similar histology but distinct pathophysiology marker expression dependent on origin. Whereas acinar-derived tumors exhibited low AGR2 were preceded by intraepithelial neoplasias (PanINs), duct-derived displayed high developed independently a PanIN stage via non-mucinous lesions. Using orthotopic...
Ductal cells have been proposed as a source of adult β cell neogenesis, but this has remained controversial. By combining lineage tracing, 3D imaging, and single-cell RNA sequencing (scRNA-seq) approaches, we show that ductal contribute to the population over time. Lineage tracing using Neurogenin3 (Ngn3)-CreERT line identified expressing endocrine master transcription factor Ngn3 were positive for δ marker somatostatin occasionally co-expressed insulin. The number hormone-expressing was...
Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer (IBC). Due to lack biomarkers able distinguish high- from low-risk cases, DCIS treated similar early IBC even though the minority untreated cases eventually become invasive. Here, we characterized 115 patient-derived mouse-intraductal (MIND) models reflecting full spectrum observed patients. Utilizing possibility follow natural progression combined with omics and imaging data, reveal multiple prognostic...
Abstract Hormone receptor-positive (HR + ) breast cancer (BC) is the most common type of among women worldwide, accounting for 70–80% all invasive cases. Patients with HR BC are commonly treated endocrine therapy, but intrinsic or acquired resistance a frequent problem, making focal point intense research. Despite this, malignancy still lacks adequate in vitro and vivo models study its initiation progression as well response to therapy. No mouse that fully mimic human disease available,...
Abstract In mammalian cell lines, the endosomal sorting complex required for transport (ESCRT)-III mediates abscission, process that physically separates daughter cells and completes division. Cep55 protein is regarded as master regulator of because it recruits ESCRT-III to midbody (MB), site abscission. However, importance this mechanism in a organism has never been tested. Here we show dispensable mouse embryonic development adult tissue homeostasis. -knockout offspring microcephaly...
In patients with pancreatic ductal adenocarcinoma (PDAC), intratumoural and intertumoural heterogeneity increases chemoresistance mortality rates. However, such morphological phenotypic diversities are not typically captured by organoid models of PDAC. Here we show that branched organoids embedded in collagen gels can recapitulate the landscape seen murine human PDAC, pronounced molecular is governed defined transcriptional programmes (notably, epithelial-to-mesenchymal plasticity),...
Ductal carcinoma in situ (DCIS) may progress to ipsilateral invasive breast cancer (iIBC), but often never will. Because DCIS is treated as early cancer, many women with harmless face overtreatment. To identify features associated progression, we developed an artificial intelligence-based morphometric analysis pipeline (AIDmap) on hematoxylin-eosin-stained (H&E) tissue sections. We analyzed 689 digitized H&Es of pure primary which 226 were diagnosed subsequent iIBC and 463 not. The...
Although initially successful, treatments with chemotherapy often fail because of the recurrence chemoresistant metastases. Since these tumors develop after treatment, resistance is generally thought to occur in response chemotherapy. However, alternative mechanisms intrinsic chemoresistance chemotherapy-naïve setting may exist but remain poorly understood. Here, we study drug-naïve murine breast cancer brain metastases (BCBMs) identify how cells growing a secondary site can acquire without...
Abstract The architecture of the mouse mammary gland is highly dynamic and constantly remodeled during pubertal development estrous cycle-driven sprouting regression alveolar side branches. During each these developmental stages, turnover driven by distinct subsets epithelial cells. Extensive previous research has shed light on unique morphological cell biological characteristics stage. However, technological shortcomings failed to capture dynamics single-cell contributions remodeling. Here,...
Abstract Mutations are abundantly present in tissues of healthy individuals, including the breast epithelium. Yet it remains unknown whether mutant cells directly induce lesion formation or first spread, leading to a field that is predisposed towards formation. To study clonal and spatial relationships between morphologically normal epithelium adjacent pre‐cancerous lesions, we developed three‐dimensional (3D) imaging pipeline combined with spatially resolved genomics on archival,...
Tracing the fate of individual cells and their progeny remains a challenging task. While imaging-based fate-mapping provides spatial information, it generally lacks complexity due to limited label diversity, resulting in diminished capture comprehensive lineages maps. Here, we introduce ′Polytope′, an epitope barcoding system capable generating up 512 unique color codes. Comprising nine tag cassettes flanked by loxP sites, Polytope allows random excision via Cre recombinase, creating codes...
Abstract The architecture of the human breast undergoes extensive remodelling throughout puberty, menstrual cycle, pregnancy, and involution with a risk accumulating genetic alterations tissue changes. Cells mutations in cancer driver genes are abundant tissues healthy individuals, but rarely develop into tumors. However, underlying mechanisms that prevent tumor formation largely unknown. We utilized clearing imaged 15 disease-free breasts resections subcellular resolution to unravel 3D...