A5088582087- Neonatal Respiratory Health Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Lung Cancer Treatments and Mutations
- Asthma and respiratory diseases
- Immune Response and Inflammation
- Tuberculosis Research and Epidemiology
- Molecular Biology Techniques and Applications
- Pediatric health and respiratory diseases
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Mycobacterium research and diagnosis
- Cancer Immunotherapy and Biomarkers
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Pulmonary Hypertension Research and Treatments
- Respiratory Support and Mechanisms
- Immunotherapy and Immune Responses
- Radiomics and Machine Learning in Medical Imaging
- Antimicrobial Peptides and Activities
- Nutrition, Genetics, and Disease
- Health, Environment, Cognitive Aging
- Cancer Genomics and Diagnostics
- Hemoglobin structure and function
- Immune Cell Function and Interaction
- Pneumonia and Respiratory Infections
- TGF-β signaling in diseases
Research Center Borstel - Leibniz Lung Center
2016-2025
German Center for Lung Research
2016-2025
University of Patras
2023
German Center for Infection Research
2006-2022
Uppsala University
2022
Giessen School of Theology
2021
University Medical Center
2018-2020
University of Lübeck
2010-2020
Clinical Research Center Kiel
2020
University Hospital Schleswig-Holstein
2016-2020
We have developed a high-throughput method for analyzing the methylation status of hundreds preselected genes simultaneously and applied it to discovery signatures that distinguish normal from cancer tissue samples. Through an adaptation GoldenGate genotyping assay implemented on BeadArray platform, state 1536 specific CpG sites in 371 (one nine per gene) was measured single reaction by multiplexed 200 ng bisulfite-treated genomic DNA. The used obtain quantitative measure level at each site....
Recently, models of macrophage activation have been revised. Macrophages stimulated with Th2 cytokines classified as alternatively activated.This article examines the expression and regulation CC chemokine ligand 18 (CCL18), a marker alternative activation, by human alveolar macrophages (AMs).AM were obtained from bronchoalveolar lavage (BAL) fluid patients idiopathic pulmonary fibrosis, sarcoidosis, or hypersensitivity pneumonitis (n = 69) healthy volunteers 22). Expression CCL18 was...
CpG-oligonucleotides (CpG-ODN), which induce signaling through Toll-like receptor 9 (TLR9), are currently under investigation as adjuvants in therapy against infections and cancer. CpG-ODN function Th-1 able to activate dendritic cells. In humans TLR9 has been described be strongly expressed B-lymphocytes, monocytes, plasmacytoid cells at low levels human respiratory We determined whether a direct interaction of bacterial DNA with the tumor themselves is possible investigated expression...
Abstract Backround Cigarette smoke exposure including biologically active lipopolysaccharide (LPS) in the particulate phase of cigarette induces activation alveolar macrophages (AM) and epithelial cells leading to production inflammatory mediators. This represents a crucial mechanism pathogenesis chronic obstructive pulmonary disease (COPD). Respiratory pathogens are major cause exacerbations recurrent cycles injury repair. The interaction between pathogen-associated molecular patterns host...
Abstract Lung cancer is still the leading cause of death from worldwide primarily because fact that most lung cancers are diagnosed at advanced stages. Overexpression high mobility group protein HMGA2 has been observed in a variety malignant tumors and often correlates with poor prognosis. Herein, expression levels were analyzed matching cancerous non‐cancerous samples 17 patients adenocarcinoma (AC) squamous cell carcinoma (SCC) real‐time quantitative RT‐PCR (qRT‐PCR). Transcript compared...
Legionella pneumophila, a Gram-negative facultative intracellular bacterium, causes severe pneumonia (Legionnaires' disease). Type I interferons (IFNs) were so far associated with antiviral immunity, but recent studies also indicated role of these cytokines in immune responses against (intracellular) bacteria. Here we show that wild-type L. pneumophila and flagellin-deficient Legionella, not lacking functional type IV secretion system Dot/Icm, or heat-inactivated induced IFNβ expression...
The solution structure and the mode of action arenicin isoform 1, an antimicrobial peptide with a unique 18-residue loop structure, from lugworm Arenicola marina were elucidated here. Arenicin folds into two-stranded antiparallel β-sheet. It exhibits high antibacterial activity at 37 4 °C against Gram-negative bacteria, including polymyxin B-resistant Proteus mirabilis. Bacterial killing occurs within minutes is accompanied by membrane permeabilization, detachment release cytoplasm....
Modification of the membrane lipid phosphatidylglycerol (PG) Staphylococcus aureus by enzymatic transfer a l-lysine residue leading to lysyl-PG converts net charge PG from -1 +1 and is thought confer resistance cationic antimicrobial peptides (AMPs). Lysyl-PG synthesis translocation outer leaflet bacterial are achieved protein MprF. Consequently, mutants lacking functional mprF gene in particular vulnerable action AMPs. Hence, we aim at elucidating whether which extent modulates binding,...
Non-small cell lung cancer (NSCLC) is characterized by early metastasis and has the highest mortality rate among all solid tumors, with majority of patients diagnosed at an advanced stage where curative therapeutic options are lacking. In this study, we identify a targetable mechanism involving TGFβ elevation that orchestrates tumor progression in disease. Substantial activation pathway was detected human tissues concomitant downregulation BAMBI, negative regulator signaling pathway....
Bacterial infections are known to cause severe health-threatening conditions, including sepsis. All attempts get this disease under control failed in the past, and especially times of increasing antibiotic resistance, leads one most urgent medical challenges our times. We designed a peptide bind with high affinity endotoxins, potent pathogenicity factors involved triggering The Pep19-2.5 reveals endotoxin neutralization efficiency vitro, here, we demonstrate its antiseptic/anti-inflammatory...
Several c-MET targeting inhibitory molecules have already shown promising results in the treatment of patients with Non-small Cell Lung Cancer (NSCLC). Combination EGFR- and c-MET-specific may overcome EGFR tyrosine kinase inhibitor (TKI) resistance. The aim this study was to allow for identification who might benefit from TKI treatments MET narrow on diagnostic assessment MET.222 tumor tissues NSCLC were analyzed concerning expression activation terms phosphorylation (Y1234/1235 Y1349)...
Targeting checkpoint inhibitors using monoclonal antibodies results in significantly better outcome of cancer patients compared to conventional chemotherapy. However, the current companion diagnostics predict response is so far suboptimal, since they base on more or less reliable immunohistochemical approaches. In order overcome these limitations, we analyzed epigenetic modifications PDCD1 (PD1), CD274 (PD-L1), and CTLA4 NSCLC tissues from 39 patients. Results were correlated with...
The origin of collagen-producing cells in lung fibrosis is unclear. involvement embryonic signaling pathways has been acknowledged and trans-differentiation epithelial discussed critically. work presented here investigates the role TGFB cytoskeleton remodeling expression Epithelial-Mesenchymal-Transition markers by Alveolar Epithelial Cells Type II tests hypothesis if human alveolar are capable production pro-fibrotic collagen. Primary type were extracted from donor tissues stimulated with...
The World Health Organization recommends standardised treatment durations for patients with tuberculosis (TB). We identified and validated a host-RNA signature as biomarker individualised therapy drug-susceptible (DS)- multidrug-resistant (MDR)-TB.Adult pulmonary TB were prospectively enrolled into five independent cohorts in Germany Romania. Clinical microbiological data whole blood RNA transcriptomic analysis collected at pre-defined time points throughout therapy. Treatment outcomes...
Background In vitro , animal model and clinical evidence suggests that tuberculosis is not a monomorphic disease, host response to protean with multiple distinct molecular pathways pathologies (endotypes). We applied unbiased clustering identify separate endotypes classifiable gene expression patterns outcomes. Methods A cohort comprised of microarray data from microbiologically confirmed patients was used putative endotypes. One longitudinal outcomes reserved for validation, as were two...
Background Virus infections drive COPD exacerbations and progression. Antiviral immunity centres on the activation of virus-specific CD8 + T-cells by viral epitopes presented major histocompatibility complex (MHC) class I molecules infected cells. These are generated immunoproteasome, a specialised intracellular protein degradation machine, which is induced antiviral cytokines in Methods We analysed effects cigarette smoke cytokine- virus-mediated induction immunoproteasome vitro , ex vivo...
Tuberculosis (TB) and sarcoidosis are both granulomatous diseases. Here, we compared the immunological microenvironments of granulomas from TB patients using in situ sequencing (ISS) transcriptomic analysis multiplexed immunolabeling tissue sections. lesions consisted large necrotic cellular granulomas, whereas “multifocal” with macrophages or epitheloid cell core a T-cell rim were observed samples. The was surrounded by encircled dense layer. Within layer, compact B-cell aggregates most...
Whereas endothelial responses to shear stress have been studied extensively, the circumferential vascular stretch are yet poorly defined. Circumferential in pulmonary microvessels is largely determined by transmural pressure gradient, hence both perfusion and alveolar ventilation pressures. Here, we production of nitric oxide (NO) synthase (eNOS) two different models intact lung: In isolated-perfused rat lungs, was induced elevation pressure. situ digital fluorescence microscopy revealed...