A5035799669- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Single-cell and spatial transcriptomics
- Hedgehog Signaling Pathway Studies
- Pancreatic and Hepatic Oncology Research
- Tumors and Oncological Cases
- Radiomics and Machine Learning in Medical Imaging
- AI in cancer detection
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer, Hypoxia, and Metabolism
- Medical Imaging and Pathology Studies
- Genetic factors in colorectal cancer
- Hippo pathway signaling and YAP/TAZ
- Cancer-related Molecular Pathways
- Hepatocellular Carcinoma Treatment and Prognosis
- Wnt/β-catenin signaling in development and cancer
- Gut microbiota and health
- Tissue Engineering and Regenerative Medicine
- Cancer-related gene regulation
- Mathematical Biology Tumor Growth
- Sarcoma Diagnosis and Treatment
- Oral and Maxillofacial Pathology
- Genomics and Chromatin Dynamics
Karolinska Institutet
2020-2024
University of Göttingen
2018-2021
Universitätsmedizin Göttingen
2018
A perimetastatic capsule is a strong positive prognostic factor in liver metastases, but its origin remains unclear. Here, we systematically quantify the capsule's extent and cellular composition 263 patients with colorectal cancer metastases to investigate clinical significance origin. We show that survival improves proportionally increasing encapsulation decreasing tumor-hepatocyte contact. Immunostaining reveals gradual zonation of capsule, transitioning from benign-like NGFR
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma with poor prognosis. RMS frequently show activity of PI3K signaling. In addition, they Hedgehog (HH) pathway activity, which predominantly seen in embryonal subtype (ERMS). Our vitro and vivo data demonstrate that Smoothened (SMO) antagonists strongly inhibit HH signaling efficiently reduce proliferation growth ERMS showing canonical due to germline mutations Ptch. Beyond tumors are also highly responsive towards...
Cell competition is a mechanism for cellular quality control based on cell-cell comparisons of fitness. Recent studies have unveiled central and complex role cell in cancer. Early tumors exploit to replace neighboring normal epithelial cells. Intestinal adenomas, example, use outcompete wild-type However, oncogenic mutations do not always confer an advantage: cells can identify mutant enforce their extrusion through competition, process termed "epithelial defense against cancer". A...
The development of skeletal muscle from immature precursors is partially driven by canonical WNT/β-catenin signaling. Rhabdomyosarcomas (RMS) are muscle-like, highly lethal cancers with a variably pronounced blockade differentiation. To investigate whether β-catenin signaling in RMS involved differentiation and aggressiveness RMS, we analyzed the effects WNT3A siRNA-mediated or pharmacologically induced knock-down on proliferation, apoptosis embryonal alveolar cell lines. While WNT pathway...
Abstract A prototypic pediatric cancer that frequently shows activation of RAS signaling is embryonal rhabdomyosarcoma (ERMS). ERMS also show aberrant Hedgehog (HH)/GLI activity and can be driven by germline mutations in this pathway. We show, cell lines derived from sporadic tumors i.e. not caused an inherited genetic variant, HH/GLI plays a subordinate role, because oncogenic HRAS , KRAS or NRAS (collectively named oncRAS) inhibit the main HH target GLI1 via MEK/ERK-axis, but...
Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid tumors. Based on transcriptomic classifiers, basal-like and classical PDAC subtypes have been defined that differ in prognosis. Cells both can coexist individual tumors; however, contribution either clonal heterogeneity or microenvironmental cues to subtype unclear. Here, we report spatial tumor phenotype dynamics a cohort patients whom infiltrated duodenal wall, identify epithelium as distinct...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor type characterized by particularly extensive stroma. While different types of cancer-associated fibroblasts (CAFs) in this desmoplastic stroma have been described, areas early invasion and nascent are understudied. Here, we identify distinctive PDAC niche within the pancreatic lobules, compartment dominated exocrine cells slender Cellular interaction profiling using machine learning on whole slide images human...
Abstract The first consensus guidelines for scoring the histopathological growth patterns (HGPs) of liver metastases were established in 2017. Since then, numerous studies have applied these guidelines, further substantiated potential clinical value HGPs patients with from various tumour types and are starting to shed light on biology distinct HGPs. In present we give an overview studies, discuss novel strategies predicting metastases, such as deep learning algorithms whole slide...
Abstract Colorectal cancer liver metastases (CRLM) grow in two major patterns defined by the histomorphology of invasion front, replacement or desmoplastic . The pattern, which a stromal rim separates tumor cells and parenchyma is strong positive prognostic factor, implying favorable biological features. However, origin perimetastatic stroma unknown underlying mechanisms are unclear. Here, we created spatial growth pattern maps resected CRLM at cell-level resolution using digital pathology...
Abstract Cellular identity in complex multicellular organisms is strictly maintained over the course of life. This control achieved part by organ structure itself, such that neighboring cells influence each other’s identity. However, large-scale investigation cellular interactome has been technically challenging. Here, we develop CIM-seq, an unsupervised and high-throughput method to analyze direct physical cell-cell interactions between every cell type a given tissue. CIM-seq based on RNA...
Single cell sequencing methods facilitate the study of tissues at high resolution, revealing rare types with varying transcriptomes or genomes, but so far have been lacking capacity to investigate cell-cell interactions. Here, we introduce CIM-seq, an unsupervised and high-throughput method analyze direct physical interactions between every type in a given tissue. CIM-seq is based on RNA incompletely dissociated cells, followed by computational deconvolution these into their constituent...
Single cell sequencing methods facilitate the study of tissues at high resolution, revealing rare types with varying transcriptomes or genomes, but so far have been lacking capacity to investigate cell-cell interactions. Here, we introduce CIM-seq, an unsupervised and high-throughput method analyze direct physical interactions between every type in a given tissue. CIM-seq is based on RNA incompletely dissociated cells, followed by computational deconvolution these into their constituent...