A5029802661- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Lung Cancer Treatments and Mutations
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Colorectal Cancer Treatments and Studies
- Cancer Cells and Metastasis
- Cancer-related gene regulation
- Radiomics and Machine Learning in Medical Imaging
- Immune cells in cancer
- Genetic factors in colorectal cancer
- Monoclonal and Polyclonal Antibodies Research
- Cancer Mechanisms and Therapy
- Effects of Environmental Stressors on Livestock
- Immune Cell Function and Interaction
- Computational Drug Discovery Methods
- Cancer Research and Treatments
- Colorectal Cancer Surgical Treatments
- Digestive system and related health
- 3D Printing in Biomedical Research
- Birth, Development, and Health
- Molecular Biology Techniques and Applications
- MicroRNA in disease regulation
- Folate and B Vitamins Research
Charles River Laboratories (Germany)
2019-2024
University of Freiburg
2014-2022
ETH Zurich
2022
University of Zurich
2022
University of Hagen
2022
Charles River Laboratories (Netherlands)
2019
German Cancer Research Center
2017-2018
Deutschen Konsortium für Translationale Krebsforschung
2017-2018
Heidelberg University
2017-2018
University of California, Santa Barbara
2014
Colorectal cancer (CRC) accounts for about 10% of deaths worldwide. Colon carcinogenesis is critically influenced by the tumor microenvironment. Cancer associated fibroblasts (CAFs) and macrophages (TAMs) represent major components TAMs promote progression, angiogenesis tissue remodeling. However, impact molecular crosstalk cells (TCs) with CAFs on monocyte recruitment their phenotypic conversion not known in detail so far. In a 3D human organotypic CRC model, we show that normal colonic are...
Pancreatic cancer (PDAC) is a highly aggressive malignancy for which the identification of novel therapies urgently needed. Here, we establish human PDAC organoid biobank from 31 genetically distinct lines, covering representative range tumor subtypes, and demonstrate that these reflect molecular phenotypic heterogeneity primary tissue. We use CRISPR-Cas9 genome editing drug screening to characterize drug-gene interactions with ARID1A BRCA2. find missense- but not frameshift mutations in...
Late diagnosis and systemic dissemination essentially contribute to the invariably poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Therefore, development diagnostic biomarkers for PDAC are urgently needed improve patient stratification outcome in clinic. By studying transcriptomes independent cohorts tumor non-tumor tissues, we identified 81 robustly regulated genes, through a novel, generally applicable meta-analysis. Using consensus clustering on co-expression values revealed...
Smoking tobacco is a known risk factor for the development of colorectal cancer and mortality associated with disease. has been reported to be changes in DNA methylation blood lung tumour tissues, although there scant investigation how epigenetic factors may implicated increased developing cancer. To identify smoking behaviours, we performed epigenome-wide analysis tumours from 36 never-smokers, 47 former smokers, 13 active adjacent mucosa 49 64 18 smokers. Our analyses identified 15 CpG...
Abstract In humans the expression of lactase changes during post-natal development, leading to phenotypes known as persistence and non-persistence. Polymorphisms within gene ( LCT ) enhancer, in particular −13910C > T, but also others, are linked these phenotypes. We were interested identifying dynamic mediators regulation, beyond genotype at T. To this end, we investigated two levels regulation human intestinal samples obtained from New England children adolescents mixed European...
DNA methylation is recognized as one of several epigenetic regulators gene expression and potential driver carcinogenesis through gene-silencing tumor suppressors activation oncogenes. However, abnormal methylation, even promoter regions, does not necessarily alter levels, especially if the already silenced, leaving exact mechanisms unanswered. Using a large cohort matching samples colorectal cancer (CRC; n = 77) normal adjacent mucosa tissues (n 108), we investigated regulatory role on...
In up to 30% of non-small cell lung cancer (NSCLC) patients, the oncogenic driver tumor growth is a constitutively activated epidermal factor receptor (EGFR). Although these patients gain great benefit from treatment with EGFR tyrosine kinase inhibitors, development resistance inevitable. To model emergence drug resistance, an EGFR-driven, patient-derived xenograft (PDX) NSCLC was treated continuously Gefitinib in vivo. Over period more than three months, separate clones developed and were...
Heart diseases are the leading cause of death for vast majority people around world, which is often due to limited capability human cardiac regeneration. In contrast, zebrafish have capacity fully regenerate their hearts after injury. Understanding and activating these mechanisms would improve health in patients suffering from long-term consequences ischemia. Therefore, we monitored dynamic transcriptome response both mRNA microRNA at 1–160 days post cryoinjury (dpi). Using a control model...
Patient-derived xenografts (PDXs) are tumour fragments engrafted into mice for preclinical studies. PDXs offer clear advantages over simpler in vitro cancer models - such as cell lines (CCLs) and organoids terms of structural complexity, heterogeneity, stromal interactions. Here, we characterise 231 colorectal at the genomic, transcriptomic, epigenetic levels, along with their response to cetuximab, an EGFR inhibitor used clinically metastatic cancer. After evaluating PDXs' quality,...
A bstract Patient-derived xenografts (PDXs) are tumour fragments engrafted into mice for preclinical studies. PDXs offer clear advantages over simpler in vitro cancer models - such as cell lines (CCLs) and organoids terms of structural complexity, heterogeneity, stromal interactions. We characterised 231 colorectal at the genomic, transcriptomic, epigenetic level measured their response to cetuximab, an EGFR inhibitor clinical use metastatic cancer. After assessing PDXs’ quality, stability,...
Abstract Folate plays an important role in the modulation of one-carbon metabolism and DNA methylation through a complex biosynthesis pathway. deficiency during pregnancy has been associated with increased risk for birth defects. This study investigates extent to which availability folate S-Adenosylmethionine (SAM) affects placental methylation. We hypothesized that maintaining sufficient levels SAM is particularly individuals carrying MTHFR C677T polymorphism. Maternal- cord blood was...
Abstract Patient-derived tumor xenograft (PDX) models have become indispensable for the preclinical profiling of novel anti-cancer agents as they retain histological, molecular and pharmacological characteristics parental patient tumors many types collectively replicate diversity tumors. To make PDX available in vitro assays, we established a panel 79 low passage cell lines derived from PDXs representing 15 different histologies. Using, among others, non-small lung cancer model LXFE_2478...
Tubulin binding drugs are approved for the treatment of many cancer types, without use molecular markers to select patients likely respond. Plinabulin binds β-tubulin in a differentiated pocket and is being tested Phase 3 clinical study NSCLC. Additional indications considered plinabulin an algorithm selecting especially responsive cancers patient subgroups would be significant value. With this mind, Affymetrix HG-U133 Plus 2.0 array mRNA expression data 43 human breast, lung, prostate,...
Abstract In the advent of immune modulatory compounds being part most oncology drug development pipelines, available preclinical models have to be characterized with respect their interaction tumor microenvironment in general and cells host specifically. current study we analyzed 31 PDX covering a broad range solid cancer entities regard phenotypic characteristics humanized environment. Well established from six different (breast, colon, renal, pancreatic, NSCL glioblastoma) were implanted...
Abstract Tubulin binding drugs are approved for the treatment of many cancer types, without use molecular markers to select patients likely respond. Plinabulin binds β-tubulin in a differentiated pocket and is being tested Phase 3 clinical study NSCLC. Additional indications considered plinabulin an algorithm selecting especially responsive cancers patient subgroups would be significant value. With this mind, Affymetrix HG-U133 Plus 2.0 array mRNA expression data 43 human breast, lung,...
Abstract Three-dimensional (3D) cell culture platforms are increasingly being used in cancer research and drug development. Using patient derived xenograft (PDX) as tumor source the clinical relevance of those increases significantly. In combination with live imaging capabilities a powerful tool for dynamic studies drug-cell interactions arises. current study we determined penetration anti-EGFR antibodies cetuximab panitumumab NSCLC spheroids different conditions (w/wo human dermal...
Abstract The epidermal growth factor receptor (EGFR, HER1, ERBB1) is a driver of many human cancers. Standard care treatment for colon, head and neck non-small cell lung cancer includes drugs targeting EGFR. Numerous molecular alterations activating the oncogenic potential EGFR gene have been described including point mutations, mutations causing resistance against EGFR-targeting drugs, deletions truncations as well overexpression its ligands, occasionally induced by amplification. In other...
Background and Hypothesis: Expression of the cardiomyocyte (CM) protein S100A1, which improves contractile performance heart, sharply increases during postnatal myocardial maturation but declines rapidly in failing hearts. We therefore hypothesized that CMs are wired with transcriptional factors (TFs) positively negatively regulate S100A1’s gene locus activity. Understanding these reciprocal circuits may be relevant for advanced therapeutic modulation abundance diseased Methods Results: H9C2...