A5040334210- Gut microbiota and health
- Microscopic Colitis
- interferon and immune responses
- Tryptophan and brain disorders
- Inflammatory Bowel Disease
- Endoplasmic Reticulum Stress and Disease
- Stress Responses and Cortisol
- Eosinophilic Esophagitis
- Digestive system and related health
- DNA Repair Mechanisms
- RNA regulation and disease
- Metabolism and Genetic Disorders
- Helicobacter pylori-related gastroenterology studies
- Autophagy in Disease and Therapy
- Cytomegalovirus and herpesvirus research
- Gastrointestinal disorders and treatments
- Dermatology and Skin Diseases
- Genomics, phytochemicals, and oxidative stress
- Galectins and Cancer Biology
- Biochemical and Molecular Research
- Autoimmune and Inflammatory Disorders Research
- Ginseng Biological Effects and Applications
- Cancer Genomics and Diagnostics
- Mosquito-borne diseases and control
- Complementary and Alternative Medicine Studies
University Hospital Schleswig-Holstein
2018-2025
Kiel University
2019-2025
University of Lübeck
2018-2025
University Medical Center
2025
Clinical Research Center Kiel
2023-2025
Universitäts Hautklinik Kiel
2025
Institute of Molecular Biology
2024
A coding variant of the inflammatory bowel disease (IBD) risk gene ATG16L1 has been associated with defective autophagy and deregulation endoplasmic reticulum (ER) function. IL-22 is a barrier protective cytokine by inducing regeneration antimicrobial responses in intestinal mucosa. We show that critically orchestrates signaling epithelium. stimulation physiologically leads to transient ER stress subsequent activation STING-dependent type I interferon (IFN-I) signaling, which augmented...
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....
Background & AimsRNase H2 is a holoenzyme, composed of 3 subunits (ribonuclease A, B, and C), that cleaves RNA:DNA hybrids removes mis-incorporated ribonucleotides from genomic DNA through ribonucleotide excision repair. Ribonucleotide incorporation by eukaryotic polymerases occurs during every round genome duplication produces the most frequent type naturally occurring lesion. We investigated whether intestinal epithelial proliferation requires RNase function activity disrupted...
Background & AimsThroughout life, the intestinal epithelium undergoes constant self-renewal from stem cells. Together with genotoxic stressors and failing DNA repair, this causes susceptibility toward malignant transformation. X-box binding protein 1 (XBP1) is a stress sensor involved in unfolded response (UPR). We hypothesized that XBP1 acts as signaling hub to regulate epithelial damage responses.MethodsData The Cancer Genome Atlas were analyzed for association of colorectal cancer (CRC)...
Abstract Background RNaseH2 plays a critical role in removing mis-bounded RNA from the DNA double strand helix1. Absence of results spontaneous double-stranded breaks and cytosolic release dsDNA2. We have previously shown that epithelial deficiency RNaseH2b (H2bΔIEC) leads to p53-dependent stem cell suppression additional p53 intestinal carcinogenesis3. Due central cGAS/STING sensing dsDNA, we aim investigate STING mouse model chronic damage tumor prevention this study. Methods was assessed...
Abstract Background Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation and metabolic dysregulation in the intestinal epithelium. Serine, a non-essential amino acid synthesized via rate-limiting enzyme phosphoglycerate dehydrogenase (PHGDH) maintains cellular redox balance. Serine metabolism upregulated cancer immune cells, supporting survival growth. Our previous story shows ER stress-mediated rewiring of serine key molecular feature IBD. However, mechanism how it...
Abstract Background The course, extent, and therapeutic response in ulcerative colitis (UC) are highly heterogeneous. spatial immunological variability of chronic inflammation UC may explain the inconsistent responses to advanced therapies. Eosinophils found both inflamed non-inflamed tissue at varying numbers, though their exact role pathophysiology clinical significance is still unclear, despite being part Geboes score criteria. We therefore aimed systematically assess characteristics...
Abstract Background Tryptophan metabolism is severely disrupted in IBD. Pro-inflammatory cytokines activate the first rate-limiting enzyme IDO1 leading to tryptophan degradation through kynurenine pathway. Although Trp typically support de novo NAD synthesis via KP activation, evidence suggests a metabolic block at downstream QPRT STING has been described as inducing secretion of type I interferons and other inflammatory cytokines, suggesting its important role regulating intestinal...
Abstract Background In IBD, clinical symptoms often do not correlate with mucosal inflammation, generating an unmet need for non- or minimally invasive biomarkers of endoscopic disease activity. Furthermore, predicting course and enabling early targeted therapy are lacking. We aimed to identify serum metabolites that distinguish healthy controls (HC) from UC patients, activity predict remission in UC. Methods Serum was collected HC (n=195) patients longitudinal (n=92) cross-sectional cohorts...
Abstract Background Stimulator of interferon genes (STING) regulates intestinal homeostasis and inflammation by detecting cytoplasmic double-stranded DNA, driving type-1 (IFN) responses.1 The autophagy-related gene ATG16L1, a major risk factor for inflammatory bowel disease (IBD), links to STING overactivation in epithelial cells (IEC), causing via IFN1, NF-κB, TNFα signaling.2 Excessive activity is associated with autoinflammatory disorders1, whereas full-body Sting knockout (Tmem173gt/gt)...
Abstract Background The kynurenine pathway is upregulated in inflammatory bowel disease (IBD) a disease-activity induced manner. This route of tryptophan (Trp) degradation leads to variety bioactive compounds, including several with anti-inflammatory (e.g., kynurenic acid (Kyna), xanthurenic (Xana)) or cytotoxic (quinolinic (Quin)) effects. Our aim was stratify patients IBD into distinct subgroups based on their Trp metabolic profiles (Trp metabotypes) and assess prognostic capacity...
Inflammatory bowel disease (IBD) is associated with perturbed metabolism of the essential amino acid tryptophan (Trp). Whether increased degradation Trp directly fuels mucosal inflammation or acts as a compensatory attempt to restore cellular energy levels via
Abstract Chronic inflammatory diseases (CID) are systems disorders affecting various organs including the intestine, joint and skin. The essential amino acid tryptophan (Trp) is not only used for protein synthesis but can also be catabolized to bioactive derivatives that important cellular energy metabolism immune regulation. Increased Trp catabolism via kynurenine pathway seen across individual CID entities 1–5 . Here, we assessed levels of 13 investigate extent nature wasting as a...
Patients with inflammatory bowel disease (IBD) are predisposed to the reactivation of viral infections such as cytomegalovirus (CMV). Clinical discrimination flares and colonic CMV is difficult in patients established diagnosis IBD, there no reliable noninvasive diagnostic tools yet. Furthermore, influence novel therapeutics including biologicals Janus kinase inhibitors on risk colitis unclear. The goal this study was identify factors clinical determinants that could serve minimally invasive...
Abstract Background The gut microbiome is an important contributor to the development and course of inflammatory bowel disease (IBD). While changes in composition were observed response IBD therapy using biologics, studies elucidating human microbial proteins pathways dependence on success are sparse. Methods Fecal samples a cohort patients collected before after 14 weeks treatment with three different biologics. Clinical activity scores used determine clinical remission. metaproteomes...
<title>Abstract</title> Metabolomics provides insights into biochemical dynamics, with nuclear magnetic resonance (NMR) being one of the few noninvasive techniques. However, traditional 1H NMR often suffers from overlapping signals proteins and numerous metabolites. To address this, we employed deuterium labeling, reducing background interference streamlining metabolic analysis. Deuterium spectroscopy (DMRS) enables rapid, measurement flux without specialized equipment. In our study, first...