A5040726327- Gut microbiota and health
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Helicobacter pylori-related gastroenterology studies
- Bone health and treatments
- RNA regulation and disease
- Colorectal Cancer Treatments and Studies
- Microscopic Colitis
- Inflammatory Bowel Disease
- Bone health and osteoporosis research
- Cancer, Lipids, and Metabolism
- Pancreatic and Hepatic Oncology Research
- interferon and immune responses
- Genomics, phytochemicals, and oxidative stress
- Gastrointestinal disorders and treatments
- Genetic factors in colorectal cancer
- Cancer Diagnosis and Treatment
- Probiotics and Fermented Foods
- Liver Disease Diagnosis and Treatment
- Gastrointestinal motility and disorders
- Diet and metabolism studies
- Heat shock proteins research
- Ginseng Biological Effects and Applications
- Colorectal Cancer Screening and Detection
- Metabolomics and Mass Spectrometry Studies
Technical University of Munich
2016-2024
University of Luxembourg
2024
Austin Health
2024
The University of Melbourne
2024
Abstract Control of intestinal epithelial stemness is crucial for tissue homeostasis. Disturbances in function are implicated inflammatory and neoplastic diseases the gastrointestinal tract. Here we report that mitochondrial plays a critical role maintaining Using cell (IEC)-specific mouse models, show loss HSP60, chaperone, activates unfolded protein response (MT-UPR) results dysfunction. HSP60-deficient crypts display proliferation, accompanied by release WNT10A RSPO1. Sporadic failure...
Activating transcription factor 6 (ATF6) regulates endoplasmic reticulum stress. We studied whether ATF6 contributes to the development of colorectal cancer (CRC) using tissue from patients and transgenic mice.We analyzed data 541 with CRC in The Cancer Genome Atlas database for genetic variants aberrant expression levels unfolded protein response genes. Findings were validated a cohort 83 Germany. generated mice intestinal epithelial cell-specific active form Atf6 (nATF6IEC) 2 alleles...
Excess and unresolved endoplasmic reticulum (ER) stress in intestinal epithelial cells (IECs) promotes inflammation. Activating transcription factor 6 (ATF6) is one of the signaling mediators ER stress. We studied pathways that regulate ATF6 its role for inflammation IECs.We performed an RNA interference screen, using 23,349 unique small interfering RNAs targeting 7783 genes a luciferase reporter controlled by ATF6-dependent ERSE (ER stress-response element) promoter, to identify proteins...
Inflammatory bowel diseases are characterized by the chronic relapsing inflammation of gastrointestinal tract. While molecular causality between endoplasmic reticulum (ER) stress and intestinal is widely accepted, metabolic consequences ER on pathophysiology IBD remain unclear. By using in vitro, vivo models, patient datasets, we identified a distinct polarization mitochondrial one-carbon metabolism fine-tuning amino acid uptake epithelial cells tailored to support GSH NADPH upon stress....
PURPOSE Suppression of ovarian function and aromatase inhibition (AI) increases disease-free survival in premenopausal women with estrogen receptor (ER)–positive early-stage breast cancer but accelerates bone loss. We therefore hypothesized that suppressing remodeling using denosumab (DMAB) would prevent loss these women. METHODS In a 12-month double-blind randomized trial, 68 ER-positive commencing suppression AI were randomly assigned to 60 mg DMAB (n = 34) or placebo (PBO; n once every 6...
Abstract Western diet is an important risk factor for the development of sporadic colorectal cancer (CRC). Dietary fat stimulates bile acid (BA) production by host and their conversion to secondary BAs 7α-dehydroxylating (7αDH+) bacteria, but causal proof tumor-promoting effects in vivo lacking. To address this, we performed feeding studies a genetically engineered pig model CRC combined with multi-omics analyses gnotobiotic mouse studies. worsened disease phenotype APC 1311/+ pigs. This was...
A multimetabo-lipid-prote-omics workflow was developed to characterize the molecular interplay within proximal (PC) and distal (DC) colonic epithelium of healthy mice. This multiomics data set lays foundation better understand two tissue types can be used study, for example, colon-related diseases like colorectal cancer or inflammatory bowel disease. First, methyl tert-butyl ether extraction method optimized, so that from a single biopsy >350 reference-matched metabolites, >1850 lipids,...
Chronic inflammation in inflammatory bowel disease (IBD) patients represents a risk factor for developing colitis-associated cancer (CAC). We previously linked the endoplasmic reticulum unfolded protein response (UPRER) signal transducer activating transcription 6 (ATF6) with spontaneous microbiota-dependent colonic adenoma development mice expressing epithelial-specific activated ATF6 (nATF6IEC). To investigate IBD-related factors ATF6-mediated tumorigenesis, we crossed tumor-free...
Abstract The induction of endoplasmic reticulum unfolded protein responses (UPR ER ) contributes to cancer development and progression. We recently linked microbiota-related triggers the tumor-promoting role signal transducer activating transcription factor 6 (ATF6) in colon. Here we substantiate clinical relevance ATF6 related bacterial genera colorectal patient cohorts. Spatial longitudinal profiling transgenic mice (nATF6 IEC identified tumor-initiating tumor-progressing shifts...
Abstract Background Colorectal cancer (CRC) is a leading cause of deaths worldwide. The endoplasmic reticulum unfolded protein response (UPRER) signal transducer activating transcription factor 6 (ATF6) clinically relevant pre-cancerous marker in CRC and colitis-associated CRC. We established the interrelated role microbiota ATF6 signalling as novel tumor-promoting mechanism our transgenic mouse model spontaneous microbiota-dependent ATF6-driven (nATF6IEC). Methods To elucidate...
Abstract Inflammatory bowel diseases (IBD) are characterized by chronic relapsing inflammation of the gastrointestinal tract. While molecular causality between endoplasmic reticulum (ER) stress and intestinal is widely accepted, metabolic consequences ER-stress on pathophysiology IBD remain unclear. By using in vitro , ex vivo mouse models patient datasets, we identified a distinct polarisation mitochondrial one-carbon (1C) metabolism fine-tuning amino acid uptake epithelial cells tailored...