A5078807718- Cancer Cells and Metastasis
- Wnt/β-catenin signaling in development and cancer
- Colorectal Cancer Treatments and Studies
- Digestive system and related health
- Cancer-related molecular mechanisms research
- Cervical Cancer and HPV Research
- MicroRNA in disease regulation
- RNA modifications and cancer
- Genetic factors in colorectal cancer
- Cancer Genomics and Diagnostics
- Head and Neck Cancer Studies
- Ubiquitin and proteasome pathways
- Ferroptosis and cancer prognosis
- Cancer-related Molecular Pathways
- Immune cells in cancer
- Hippo pathway signaling and YAP/TAZ
- Circular RNAs in diseases
- Reproductive tract infections research
- CAR-T cell therapy research
- Cancer-related gene regulation
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Cell Function and Interaction
- Endoplasmic Reticulum Stress and Disease
- Cancer, Hypoxia, and Metabolism
- Estrogen and related hormone effects
DKFZ-ZMBH Alliance
2023-2025
Heidelberg University
2018-2025
German Cancer Research Center
2018-2025
Georg Speyer Haus
2018-2023
Goethe University Frankfurt
2018-2023
University of Münster
2021-2023
Deutschen Konsortium für Translationale Krebsforschung
2018-2023
Frankfurt Cancer Institute
2019-2023
Weizmann Institute of Science
2023
Imperial College London
2023
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...
Recently, a transcriptome-based consensus molecular subtype (CMS) classification of colorectal cancer (CRC) has been established, which may ultimately help to individualize CRC therapy. However, the lack animal models that faithfully recapitulate different subtypes impedes adequate preclinical testing stratified therapeutic concepts. Here, we demonstrate constitutive AKT activation in intestinal epithelial cells markedly enhances tumor invasion and metastasis Trp53ΔIEC mice...
CD4+ T cells are vital for host defense and immune regulation. However, the fundamental role of CD4 itself remains enigmatic. We report seven patients aged 5–61 years from five families four ancestries with autosomal recessive deficiency a range infections, including recalcitrant warts Whipple’s disease. All homozygous rare deleterious variants impacting expression canonical isoform. A shorter expressed isoform that interacts LCK, but not HLA class II, is affected by only one variant. lack...
Constitutive Wnt activation upon loss of Adenoma polyposis coli (APC) acts as main driver colorectal cancer (CRC). Targeting signaling has proven difficult because the pathway is crucial for homeostasis and stem cell renewal. To distinguish oncogenic from physiological activity, we have performed transcriptome proteome profiling in isogenic human colon organoids. Culture presence or absence exogenous ligand allowed us to discriminate receptor-mediated effects CRISPR/Cas9-induced APC loss. We...
Tumor immunosuppression is a limiting factor for successful cancer therapy. The lipid sphingosine-1-phosphate (S1P), which signals through 5 distinct G protein–coupled receptors (S1PR1–5), has emerged as an important regulator of carcinogenesis. However, the utility targeting S1P in tumors hindered by S1P's impact on immune cell trafficking. Here, we report that ablation cell–specific receptor S1PR4, plays minor role trafficking, delayed tumor development and improved therapy success murine...
Brain-resident microglia and bone marrow-derived macrophages represent the most abundant non-cancerous cells in brain tumor microenvironment with critical functions disease progression therapeutic response. To date little is known about genetic programs that drive disease-associated phenotypes of metastases. Here we used cytometric transcriptomic analyses to define cellular molecular changes myeloid compartment at distinct stages metastasis response radiotherapy. We demonstrate programming...
Abstract Background Breast cancer is the leading cause of cancer-related mortality in women. Deregulation miRNAs frequently observed breast and affects tumor biology. A pre-miRNA, such as pre-miR-1307, gives rise to several mature miRNA molecules with distinct functions. However, impact global deregulation pre-miR-1307 its individual has not been investigated cancer, yet. Results Here, we found significant upregulation three species derived from human tissue. Surprisingly, overexpression...
Abstract Individuals living with HIV are at a higher risk for developing human papillomavirus-driven oropharyngeal squamous cell carcinoma (HPV+OPSCC). There no methods early detection; however, HPV16 E6 antibodies have been identified as promising marker. The objective of this study was to evaluate the prevalence among men HIV, secondary objectives analyzing clinical and serologic predictors seropositivity. Banked blood specimens from 2,320 aged 40+ in Tennessee were evaluated following...
<div>Abstract<p>Individuals living with human immunodeficiency virus (HIV) are at a higher risk for developing papillomavirus–driven oropharyngeal squamous cell carcinoma (HPV + OPSCC). There no methods early detection; however, HPV16 E6 antibodies have been identified as promising marker. The objective of this study was to evaluate the prevalence among men HIV, secondary objectives analyzing clinical and serologic predictors seropositivity. Banked blood specimens from 2,320 ages...
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...
Intestinal epithelial cells absorb nutrients through the brush border, composed of dense arrays highly ordered microvilli at their apical membranes. A protocadherin-based intermicrovillar adhesion complex localized tips mediates packing and organization. Here, we identified a second proximal base region microvilli. This contained immunoglobulin superfamily member TMIGD1, which directly interacted with microvillar scaffolding proteins EBP50 E3KARP. Complex formation required activation by...
Abstract Background HPV-associated oropharyngeal cancer (HPV+OPSCC) is the most common in United States yet unlike cervical lacks a screening test. HPV+OPSCCs are presumed to start developing 10-15 years prior clinical diagnosis. Circulating tumor HPV DNA (ctHPVDNA) sensitive and specific biomarker for HPV+OPSCC. Taken together, blood-based HPV+OPSCC may be feasible Methods We developed an whole genome sequencing assay, HPV-DeepSeek, with 99% sensitivity specificity at 28 plasma samples from...
Abstract HER3 is highly expressed in luminal breast cancer subtypes. Its activation by NRG1 promotes of AKT and ERK1/2, contributing to tumour progression therapy resistance. HER3-targeting agents that block this activation, are currently under phase 1/2 clinical studies, although they have shown favorable tolerability, their activity as a single agent has proven be limited. Here we show phosphorylation cells occurs paracrine manner mediated cancer-associated fibroblasts (CAFs). Moreover,...
Abstract MicroRNAs (miRNAs) are small non-coding RNAs with diverse functions in post-transcriptional regulation of gene expression. Sequence and length variants miRNAs called isomiRs can exert different compared to their canonical counterparts. The Cancer Genome Atlas (TCGA) provides isomiR-level expression data for patients various cancer entities collected a multi-center approach over several years. However, the impact batch effects within individual cohorts has not been systematically...
<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...
MicroRNAs (miRNAs) and isomiRs play important roles in tumorigenesis as essential regulators of gene expression. 5'isomiRs exhibit a shifted seed sequence compared to the canonical miRNA, resulting different target spectra thereby extending phenotypic impact respective common pre-miRNA. However, for most miRNAs, expression function have not been studied detail yet. Therefore, this study aims investigate functions miRNAs their 5'isomiRs.The was assessed The Cancer Genome Atlas (TCGA) breast...
Abstract Intratumoral heterogeneity impacts the success or failure of anti-cancer therapies. Here, we investigated evolution and mechanistic in clonal populations cell models for estrogen receptor positive breast cancer. To this end, established barcoded luminal cancer rendered them resistant to commonly applied first line endocrine By isolating single clones from pools characterizing replicates individual observed inter- (between lines) intra-tumor different same line) heterogeneity....