A5029180699- Fibroblast Growth Factor Research
- Cancer, Lipids, and Metabolism
- Cancer, Hypoxia, and Metabolism
- Liver Disease Diagnosis and Treatment
- Cancer Research and Treatments
- Epigenetics and DNA Methylation
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Cancer-related Molecular Pathways
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Mast cells and histamine
- RNA modifications and cancer
- Liver Disease and Transplantation
- Ferroptosis and cancer prognosis
- Invertebrate Taxonomy and Ecology
- Glioma Diagnosis and Treatment
- Pancreatic and Hepatic Oncology Research
- Lipid metabolism and biosynthesis
- Advanced biosensing and bioanalysis techniques
- Nanoplatforms for cancer theranostics
- CRISPR and Genetic Engineering
- Phagocytosis and Immune Regulation
- Radiomics and Machine Learning in Medical Imaging
- Plant and animal studies
Comprehensive Cancer Center Vienna
2016-2025
Medical University of Vienna
2016-2025
University of Vienna
2014
Insects are the most speciose group of animals, but phylogenetic relationships many major lineages remain unresolved. We inferred phylogeny insects from 1478 protein-coding genes. Phylogenomic analyses nucleotide and amino acid sequences, with site-specific or domain-specific substitution models, produced statistically robust congruent results resolving previously controversial relations hips. dated origin to Early Ordovician [~479 million years ago (Ma)], insect flight Devonian (~406 Ma),...
Tumor-infiltrating immune cells are highly relevant for prognosis and identification of immunotherapy targets in hepatocellular carcinoma (HCC). The recently developed CIBERSORT method allows cell profiling by deconvolution gene expression microarray data. By applying CIBERSORT, we assessed the relative proportions 41 healthy human livers, 305 HCC samples 82 adjacent tissues. obtained profiles provided enumeration activation status 22 subtypes. Mast were evaluated immunohistochemistry ten...
Abstract Prime editing (PE) is a powerful genome engineering approach that enables the introduction of base substitutions, insertions and deletions into any given genomic locus. However, efficiency PE varies widely depends not only on region targeted, but also genetic background edited cell. Here, to determine which cellular factors affect efficiency, we carry out focused screen targeting 32 DNA repair factors, spanning all reported pathways. We show that, depending cell line type edit,...
Transforming growth factor (TGF)-β suppresses early hepatocellular carcinoma (HCC) development but triggers pro-oncogenic abilities at later stages. Recent data suggest that the receptor tyrosine kinase Axl causes a TGF-β switch toward dedifferentiation and invasion of HCC cells. Here, we analyzed two human cellular models with opposing phenotypes in response to TGF-β. Both showed reduced proliferation clonogenic behavior following stimulation, although they exhibited differences...
Polymerase theta (POLθ) is an error-prone DNA polymerase whose loss synthetically lethal in cancer cells bearing breast susceptibility proteins 1 and 2 (BRCA1/2) mutations. To investigate the basis of this genetic interaction, we utilized a small-molecule inhibitor targeting POLθ domain. We found that processes single-stranded (ssDNA) gaps emerge absence BRCA1, thus promoting unperturbed replication fork progression survival BRCA1 mutant cells. A genome-scale CRISPR-Cas9 knockout screen...
Inhibitors of the epidermal growth factor receptor (EGFR) are first-line therapy for patients with metastatic colorectal tumors without RAS mutations. However, EGFR inhibitors ineffective in these patients, and tumor level does not associate response to therapy. We screened human EGFR-positive myeloid cells investigated their association patient outcome. also performed studies mice evaluate how expression contributes development colitis-associated cancer Apc
Studying the intracellular distribution of pharmacological agents, including anticancer compounds, is central importance in biomedical research. It constitutes a prerequisite for better understanding molecular mechanisms underlying drug action and resistance development. Hyperactivated fibroblast growth factor receptors (FGFRs) constitute promising therapy target several types malignancies lung cancer. The clinically approved small-molecule FGFR inhibitor nintedanib exerts strong...
Metal-driven self-assembly afforded a multitude of fascinating supramolecular coordination complexes (SCCs) with applications as catalysts, host-guest, and stimuli-responsive systems. However, the interest in biological SCCs is only starting to emerge thorough characterization their behavior milieus still lacking. Herein, we report on synthesis detailed in-cell tracking Pt
Increased fatty acid (FA) flux from adipose tissue to the liver contributes development of NAFLD. Because free FAs are key lipotoxic triggers accelerating disease progression, inhibiting triglyceride lipase (ATGL)/patatin-like phospholipase domain containing 2 (PNPLA2), main enzyme driving lipolysis, may attenuate steatohepatitis.Hepatocyte-specific ATGL knockout (ATGL LKO) mice were challenged with methionine-choline-deficient (MCD) or high-fat high-carbohydrate (HFHC) diet. Serum...
Liver fibrosis is the static and main (70%-80%) component of portal hypertension (PH). We investigated dynamic components PH by a three-dimensional analysis based on correlation hepatic collagen proportionate area (CPA) with pressure (PP) in animals or HVPG patients.Different animal models (bile duct ligation: n = 31, carbon tetrachloride: 12, thioacetamide: choline-deficient high-fat diet: 12) patients confirmed single etiology cholestatic (primary biliary cholangitis/primary sclerosing...
Abstract Background & Aims Experimental evidence indicates that systemic inflammation (SI) promotes liver fibrogenesis. This study investigated the potential link between SI and fibrogenesis in patients with advanced chronic disease (ACLD). Methods Serum biomarkers of (CRP, IL‐6, procalcitonin [PCT]) extracellular matrix (ECM) turnover (i.e., fibrogenesis/fibrolysis) were analysed 215 prospectively recruited ACLD (hepatic venous pressure gradient [HVPG] ≥6 mm Hg) undergoing hepatic vein...
Abstract Polyploidization frequently precedes tumorigenesis but also occurs during normal development in several tissues. Hepatocyte ploidy is controlled by the PIDDosome and regeneration. This multi‐protein complex activated supernumerary centrosomes to induce p53 restrict proliferation of polyploid cells, otherwise prone for chromosomal instability. deficiency liver results drastically increased polyploidy. To investigate PIDDosome‐induced p53‐activation pathogenesis cancer, we chemically...
Abstract Background Anaplastic large cell lymphoma (ALCL) is an aggressive non-Hodgkin T commonly driven by NPM-ALK. AP-1 transcription factors, cJUN and JUNb, act as downstream effectors of NPM-ALK transcriptionally regulate PDGFRβ. Blocking PDGFRβ kinase activity with imatinib effectively reduces tumor burden prolongs survival, although the molecular mechanisms remain elusive. Methods results In a transgenic mouse model that mimics PDGFRβ-driven human ALCL in vivo, we identify driver...
Insufficient supplementation with the micronutrient selenium and persistent hepatic inflammation predispose to hepatocellular carcinoma (HCC). Inflammation-associated reactive oxygen species attack membrane lipids form lipid hydroperoxides able propagate oxidative damage. Selenium-containing enzyme glutathione peroxidase 4 (GPx4) antagonizes this damage by reducing respective hydroxides. However, role of GPx4 in HCC remains elusive. We generated two human cell lines stable overexpression...
The interferon‐inducible transcription factor STAT1 is a tumor suppressor in various malignancies. We investigated sex‐specific functions colitis and colitis‐associated colorectal cancer (CRC) using mice with specific deletion intestinal epithelial cells (STAT1 ∆IEC ). Male but not female were more resistant to DSS‐induced than sex‐matched flox/flox controls displayed reduced intraepithelial infiltration of CD8 + TCRαβ granzyme B T cells. Moreover, DSS treatment failed induce expression...
Abstract Tumors have evolved mechanisms to escape anti-tumor immunosurveillance. They limit humoral and cellular immune activities in the stroma render tumors resistant immunotherapy. Sensitizing tumor cells attack is an important strategy revert immunosuppression. However, underlying of are still poorly understood. Here we discover Indoleamine-2,3-dioxygenase-1 (IDO1) + Paneth stem cell niche intestinal crypts tumors, which promoted colorectal cancer (CRC). Ido1 expression was strictly...
Background In cirrhosis, the nitric oxide‐soluble guanylyl cyclase (sGC)‐cyclic guanosine monophosphate (cGMP) pathway is impaired, which contributes to increased intrahepatic vascular resistance (IHVR) and fibrogenesis. We investigated if sGC stimulation (riociguat (RIO)), activation (cinaciguat (CINA)) or phosphodiesterase (PDE)‐5 inhibition (tadalafil (TADA)) improves portal hypertension (PHT) liver fibrosis. Methods Fifty male Sprague–Dawley rats underwent bile‐duct ligation (BDL) sham...
Intestinal epithelial cells are covered by the brush border, which consists of densely packed microvilli. The Intermicrovillar Adhesion Complex (IMAC) links microvilli and is required for proper border organization. Whether microvillus crosslinking involved in intestinal barrier function or colitis currently unknown. We investigate role mice with deletion IMAC component CDHR5. Electron microscopy shows pronounced defects CDHR5-deficient mice. result severe mucosal damage after exposure to...
Anaplastic Large Cell Lymphoma (ALCL) is an aggressive T-cell lymphoma affecting children and young adults. About 30% of patients develop therapy resistance therefore new precision medicine drugs are highly warranted. Multiple rounds structure-activity optimization Caffeic Acid Phenethyl Ester have resulted in CM14. CM14 causes upregulation genes involved oxidative stress response downregulation DNA replication leading to G2/M arrest subsequent apoptosis induction. In accordance with this,...
Anaplastic Large Cell Lymphoma (ALCL) is an aggressive T-cell lymphoma affecting children and young adults. About 30% of patients develop therapy resistance therefore new precision medicine drugs are highly warranted. Multiple rounds structure-activity optimization Caffeic Acid Phenethyl Ester have resulted in CM14. CM14 causes upregulation genes involved oxidative stress response downregulation DNA replication leading to G2/M arrest subsequent apoptosis induction. In accordance with this,...
Enhanced protein expression of ALL1-fused gene from chromosome 1q (AF1Q) after (chemo)radiotherapy has been described in vitro, but is largely understudied gastrointestinal cancer. We aimed to investigate AF1q rectal cancer (RC) patients treated with short-term radiation therapy and a possible correlation markers crucial for RC prognosis. A cohort 75 scheduled surgery was defined moderately locally advanced tumors (cT3Nx) received preoperative hyperfractionated (cumulative dose 25 Gy)....
Polystyrene micro- and nanoplastics (PS-MNPs) are emerging environmental pollutants with potential implications for human health. In this study, we used two different sizes of PS-MNPs (0.25 um 1 um) on non-small cell lung cancer (A549, H460), small (DMS53, H372), normal epithelial (BEAS-2B) cells, as well human-derived organoids, to investigate the cytotoxic effects PS particles. At lower concentrations (< 30 ug/cm2, equivalent 50 ug/ml), neither PS-MPs nor PS-NPs did not interfere...
Small cell lung cancer (SCLC) is an aggressive malignancy with distinct molecular subtypes defined by transcription factors and inflammatory characteristics. This follow-up study aimed to validate the unique metabolic phenotype in achaete-scute homologue 1 (ASCL1)-driven SCLC lines human tumor tissue. Metabolic alterations were analyzed using proteomic data. Structural functional differences of mitochondria investigated qPCR, flow cytometry, confocal imaging, transmission electron microscopy...