A5046056275- Cancer Cells and Metastasis
- Digestive system and related health
- Colorectal Cancer Treatments and Studies
- Genetic factors in colorectal cancer
- Wnt/β-catenin signaling in development and cancer
- Immune cells in cancer
- CRISPR and Genetic Engineering
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Head and Neck Cancer Studies
- Pluripotent Stem Cells Research
- Hormonal Regulation and Hypertension
- Genetic Syndromes and Imprinting
- Renal and related cancers
- CAR-T cell therapy research
- Estrogen and related hormone effects
- DNA Repair Mechanisms
- Cytokine Signaling Pathways and Interactions
- Microtubule and mitosis dynamics
- Radiomics and Machine Learning in Medical Imaging
- Lung Cancer Treatments and Mutations
German Cancer Research Center
2025
Heidelberg University
2025
Georg Speyer Haus
2018-2025
Frankfurt Cancer Institute
2020-2024
Goethe University Frankfurt
2020-2024
In colorectal cancers, the tumor microenvironment plays a key role in prognosis and therapy efficacy. Patient-derived organoids (PDTO) show enormous potential for preclinical testing; however, cultured cells lose important characteristics, including consensus molecular subtypes (CMS). To better reflect cellular heterogeneity, we established cancer organoid-stroma biobank of matched PDTOs cancer-associated fibroblasts (CAF) from 30 patients. Context-specific phenotyping showed that...
Tumor progression is recognized as a result of an evolving cross-talk between tumor cells and their surrounding nontransformed stroma. Although Wnt signaling has been intensively studied in colorectal cancer, it remains unclear whether activity the tumor-associated stroma contributes to malignancy. To specifically interfere with stromal signals, we generated Wnt-independent organoids that secrete antagonist Sfrp1. Subcutaneous transplantation into immunocompetent well immunodeficient mice...
Head and neck cancers (HNC) represent an extremely heterogeneous group of diseases with a poorly predictable therapy outcome. Patient-derived tumor organoids (PDTO) offer enormous potential for individualized testing better mechanistic understanding the main HNC drivers. Here, we have established comprehensive molecularly functionally characterized head organoid biobank (HNOB) recapitulating clinically relevant subtypes TP53 mutant human papillomavirus type 16 (HPV 16) infection-driven HNC....
Microvillus inclusion disease (MVID) is a congenital intestinal malabsorption disorder caused by defective apical vesicular transport. Existing cellular models do not fully recapitulate this heterogeneous pathology. The aim of study was to characterize 3-dimensional organoids that continuously generate polarized absorptive cells as an accessible and relevant model investigate MVID.Intestinal from Munc18-2/Stxbp2-null mice are deficient for transport were subjected enterocyte-specific...
Control of tumour development and growth by the immune system critically defines patient fate survival. What regulates escape colorectal tumours from destruction remains currently unclear. Here, we investigated role intestinal synthesis glucocorticoids in during an inflammation-induced mouse model cancer. We demonstrate that local immunoregulatory has dual roles regulation inflammation development. In phase, LRH-1/Nr5A2-regulated Cyp11b1-mediated glucocorticoid prevents growth. established...
<h3>Background</h3> The actin cytoskeleton has a crucial role in the maintenance of immune homeostasis by controlling various cellular processes, including cell migration. Mutations <i>TTC7A</i> have been described as cause primary immunodeficiency associated to different degrees gut involvement and alterations dynamics. <h3>Objectives</h3> This study investigates impact TTC7A deficiency homeostasis. In particular, TTC7A/phosphatidylinositol 4 kinase type III α pathway control leukocyte...
<div>Abstract<p>In colorectal cancers (CRC) the tumor microenvironment plays a key role for prognosis and therapy efficacy. Patient-derived organoids (PDTOs) show enormous potential preclinical testing, however, cultured cells lose important characteristics including ‘consensus molecular subtypes’ (CMS). To better reflect cellular heterogeneity, we established CRC organoid-stroma biobank of matched PDTOs cancer-associated fibroblasts (CAFs) from 30 patients. Context-specific...
Abstract The EMT-transcription factor ZEB1 is heterogeneously expressed in tumor cells and cancer-associated fibroblasts (CAFs) colorectal cancer (CRC). While regulates metastasis therapy resistance, its role CAFs largely unknown. Combining fibroblast-specific Zeb1 deletion with immunocompetent mouse models of CRC, we observe that inflammation-driven tumorigenesis accelerated, whereas invasion sporadic cancers reduced upon loss . Single-cell transcriptomics, histological vitro...
Abstract The EMT-transcription factor ZEB1 is heterogeneously expressed in tumor cells and cancer-associated fibroblasts (CAFs) colorectal cancer (CRC). While regulates metastasis therapy resistance, its role CAFs largely unknown. Combining fibroblast-specific Zeb1 deletion with immunocompetent mouse models of CRC, we observe that inflammation-driven tumorigenesis accelerated, whereas invasion sporadic cancers are reduced. Single-cell transcriptomics, histological characterization, vitro...
<p>Supplementary Figure S1 shows light microscopic images of CRC organoids and CAFs. Supplementary S2 immunostaining RNA sequencing analysis cultured S3 chromosomal copy number changes in tumors matched organoids. S4 the transcriptional variation among S5 classification cancer intrinsic subtypes (CRIS) tumors, xenotransplants. S6 tissue microarray tumor samples from colorectal organoid-stroma biobank cohort. S7 association growth characteristics with molecular features biobank. S8 CMS...
<p>Supplementary Figure S1 shows light microscopic images of CRC organoids and CAFs. Supplementary S2 immunostaining RNA sequencing analysis cultured S3 chromosomal copy number changes in tumors matched organoids. S4 the transcriptional variation among S5 classification cancer intrinsic subtypes (CRIS) tumors, xenotransplants. S6 tissue microarray tumor samples from colorectal organoid-stroma biobank cohort. S7 association growth characteristics with molecular features biobank. S8 CMS...
<p>In this file we provide additional methods for the described procedures including organoid transduction/transgenesis, biological image processing and quantification. We in-depth information on RNA sequencing protocol used describe details of subsequent bioinformatic workflows 'NicheNet' analysis. Also in silico analysis CRC patient data Kaplan-Meier analysis.</p>
<p>In this file we provide additional methods for the described procedures including organoid transduction/transgenesis, biological image processing and quantification. We in-depth information on RNA sequencing protocol used describe details of subsequent bioinformatic workflows 'NicheNet' analysis. Also in silico analysis CRC patient data Kaplan-Meier analysis.</p>
<div>Abstract<p>Tumor progression is recognized as a result of an evolving cross-talk between tumor cells and their surrounding nontransformed stroma. Although Wnt signaling has been intensively studied in colorectal cancer, it remains unclear whether activity the tumor-associated stroma contributes to malignancy. To specifically interfere with stromal signals, we generated Wnt-independent organoids that secrete antagonist Sfrp1. Subcutaneous transplantation into immunocompetent...
<div>Abstract<p>Tumor progression is recognized as a result of an evolving cross-talk between tumor cells and their surrounding nontransformed stroma. Although Wnt signaling has been intensively studied in colorectal cancer, it remains unclear whether activity the tumor-associated stroma contributes to malignancy. To specifically interfere with stromal signals, we generated Wnt-independent organoids that secrete antagonist Sfrp1. Subcutaneous transplantation into immunocompetent...
<p>Supplementary Data Tables S1-S8 - Table S1. Details of all antibodies (A) and primer sequences (B) used in this study, S2. Differentially expressed genes tumor organoids cultured vitro, S3. FACS-purified cells after organoid transplantation, S4. CAFs S5. mouse fibroblasts S6. Summary GSEA results, S7. iCAF myCAF signatures, S8. identified human CRC upon xenotransplantation.</p>
<p>Figure S1. Generation of engineered tumor organoids, Figure S2. Characterization Sfrp1-expressing organoids in vitro and upon transplantation, S3. APTK S4. Dkk1-expressing S5. Immunohistology tumors after transplantation NSG Bl/6 mice, S6. Study growth xenotransplantation human CRC S7. Analysis stromal gene expression xenotransplantation, S8. Co-culture model to study the influence fibroblast differentiation on S9. 'NicheNet' analysis for identification candidate mediators...
<p>Figure S1. Generation of engineered tumor organoids, Figure S2. Characterization Sfrp1-expressing organoids in vitro and upon transplantation, S3. APTK S4. Dkk1-expressing S5. Immunohistology tumors after transplantation NSG Bl/6 mice, S6. Study growth xenotransplantation human CRC S7. Analysis stromal gene expression xenotransplantation, S8. Co-culture model to study the influence fibroblast differentiation on S9. 'NicheNet' analysis for identification candidate mediators...
<p>Supplementary Data Tables S1-S8 - Table S1. Details of all antibodies (A) and primer sequences (B) used in this study, S2. Differentially expressed genes tumor organoids cultured vitro, S3. FACS-purified cells after organoid transplantation, S4. CAFs S5. mouse fibroblasts S6. Summary GSEA results, S7. iCAF myCAF signatures, S8. identified human CRC upon xenotransplantation.</p>
<div>Abstract<p>In colorectal cancers (CRC) the tumor microenvironment plays a key role for prognosis and therapy efficacy. Patient-derived organoids (PDTOs) show enormous potential preclinical testing, however, cultured cells lose important characteristics including ‘consensus molecular subtypes’ (CMS). To better reflect cellular heterogeneity, we established CRC organoid-stroma biobank of matched PDTOs cancer-associated fibroblasts (CAFs) from 30 patients. Context-specific...