A5069969867- Cell Adhesion Molecules Research
- Neonatal Respiratory Health Research
- Peptidase Inhibition and Analysis
- Protease and Inhibitor Mechanisms
- Antimicrobial Peptides and Activities
- Tracheal and airway disorders
- HER2/EGFR in Cancer Research
- Immune Response and Inflammation
- Oral microbiology and periodontitis research
- Inhalation and Respiratory Drug Delivery
- Signaling Pathways in Disease
- Antibiotic Resistance in Bacteria
- Biochemical and Structural Characterization
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Extracellular vesicles in disease
- Olfactory and Sensory Function Studies
- Bacterial Infections and Vaccines
- Bacterial biofilms and quorum sensing
- Biochemical Analysis and Sensing Techniques
- Medical Imaging and Pathology Studies
- Pregnancy and preeclampsia studies
- Oral and gingival health research
- Cancer Cells and Metastasis
- Macrophage Migration Inhibitory Factor
- Microfluidic and Bio-sensing Technologies
Saarland University
2020-2025
RWTH Aachen University
2020-2023
Universitätsklinikum Aachen
2023
Memorial Sisli Hospital
2005
Acute respiratory distress syndrome (ARDS) results in catastrophic lung failure and has an urgent, unmet need for improved early recognition therapeutic development. Neutrophil influx is a hallmark of ARDS associated with the release tissue-destructive immune effectors, such as matrix metalloproteinases (MMPs) membrane-anchored metalloproteinase disintegrins (ADAMs). Here, we observed using intravital microscopy that Adam8-/- mice had impaired neutrophil transmigration. In mouse pneumonia...
Probiotic bacteria, such as Lactobacilli, have been shown to elicit beneficial effects in various tissue regeneration applications. However, their formulation living bacteria is challenging, and therapeutic use proliferating microorganisms especially limited immunocompromised patients. Here, we propose a new avenue circumvent these shortcomings by developing bacteriomimetic hydrogel based on membrane vesicles (MVs) produced Lactobacilli. We coupled MVs from Lactobacillus plantarum casei,...
Abstract Tracheal tuft cells shape immune responses in the airways. While some of these effects have been attributed to differential release either acetylcholine, leukotriene C4 and/or interleukin-25 depending on activating stimuli, cell-dependent mechanisms underlying recruitment and activation are incompletely understood. Here we show that Pseudomonas aeruginosa infection activates mouse cells, which ATP via pannexin 1 channels. Taste signaling through Trpm5 channel is essential for...
Abstract The ubiquitous opportunistic pathogen Pseudomonas aeruginosa is responsible for severe infections and notoriously known acquiring antimicrobial resistance. Inhibiting the bacterium's extracellular elastase, LasB – a zinc‐dependent protease presents promising strategy to mitigate its virulence. Within this medicinal chemistry–driven hit‐to‐lead optimization campaign, new series of highly potent dipeptidic phosphonates designed synthesized following structure–based drug‐discovery...
Abstract The metalloproteinase ADAM10 critically contributes to development, inflammation, and cancer can be controlled by endogenous or synthetic inhibitors. Here, we demonstrate for the first time that loss of proteolytic activity either inhibition function mutations induces removal protease from cell surface whole cell. This process is temperature dependent, restricted mature ADAM10, associated with an increased internalization, lysosomal degradation, release in extracellular vesicles....
Abstract The median eminence (ME) is a circumventricular organ at the base of brain that controls body homeostasis. Tanycytes are its specialized glial cells constitute ventricular walls and regulate different physiological states, however individual signaling pathways in these incompletely understood. Here, we identify functional tanycyte subpopulation expresses key taste transduction genes including bitter receptors, G protein gustducin gustatory ion channel TRPM5 (M5). M5 tanycytes have...
Abstract Chronic lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis are incurable. Epithelial senescence, a state of dysfunctional cell cycle arrest, contributes to the progression diseases. Therefore, epithelial cells valuable target for therapeutic intervention. Here, we present 3D airway organoid platform preclinical testing active substances with regard toxicity, inflammation under standardized conditions in 96 well format. Senescence was induced doxorubicin...
Abstract Background Tumor cells release extracellular vesicles (EVs) that contribute to the polarization of macrophages towards tumor-associated (TAMs). High expression levels RNA binding protein IGF2BP2/IMP2 are correlated with increased tumor cell proliferation, invasion, and poor prognosis in clinic. However, there is a lack understanding whether IMP2 affects cargo cancer cell-derived EVs, thereby modulating macrophage polarization. Methods EVs were isolated from IMP2-expressing HCT116...
The transmembrane protease A Disintegrin And Metalloproteinase 10 (ADAM10) displays a "pattern regulatory function," by cleaving range of membrane-bound proteins. In endothelium, it regulates barrier function, leukocyte recruitment and angiogenesis. Previously, we showed that ADAM10 is expressed in human atherosclerotic plaques associated with neovascularization. this study, aimed to determine the causal relevance endothelial murine atherosclerosis development vivo.Endothelial Adam10...
Pneumonia is a life-threatening disease often caused by infection with Streptococcus pneumoniae and Pseudomonas aeruginosa. Many of the mediators (e.g., TNF, IL-6R) junction molecules E-cadherin) orchestrating inflammatory cell recruitment loss barrier integrity are proteolytically cleaved through disintegrin metalloproteinases (ADAMs). We could show Western blot, surface expression analysis measurement proteolytic activity in cell-based assays, that ADAM10 epithelial cells upregulated...
Understanding the mechanisms of modulators' action on enzymes is crucial for optimizing and designing pharmaceutical substances. The acute inflammatory response, in particular, regulated mainly by a disintegrin metalloproteinase (ADAM) 17. ADAM17 processes several disease mediators such as TNFα APP, releasing their soluble ectodomains (shedding). A malfunction this process leads to disturbed response. Chemical protease inhibitors TAPI-1 were used past inhibit proteolytic activity. However,...
Uptake of bacteria by phagocytes is a crucial step in innate immune defence. Members the disintegrin and metalloproteinase (ADAM) family critically control response limited proteolysis surface expressed mediator molecules. Here, we investigated significance ADAM17 its regulatory adapter molecule iRhom2 for bacterial uptake phagocytes. Inhibition activity led to increased phagocytosis pHrodo labelled Gram-negative -positive (E. coli S. aureus, respectively) human murine monocytic cell lines...
Abstract Impaired interaction of fibroblasts with pneumocytes contributes to the progression chronic lung disease such as idiopathic pulmonary fibrosis (IPF). Mucin 5B (MUC5B) is associated IPF. Here we analyzed primary and alveolar type 2 (AT2) in organoid model. Single-cell analysis, histology, qRT-PCR revealed that expressing high levels markers regulate STAT3 signaling AT2 cells, which accompanied by cystic growth MUC5B expression. Cystic expression were also caused cytokine IL-6. The...
Calcium-selective transient receptor potential Vanilloid 6 (TRPV6) channels are expressed in fetal labyrinth trophoblasts as part of the feto–maternal barrier, necessary for sufficient calcium supply, embryo growth, and bone development during pregnancy. Recently, we have shown a less- compact morphology Trpv6-deficient placentae, reduced Ca2+ uptake primary upon functional deletion TRPV6. Trpv6-/- show distinct calcium-dependent phenotype. Deep proteomic profiling wt using label-free...
As an alternative to technically demanding and ethically debatable animal models, the use of organotypic disease-relevant human cell culture models may improve throughput, speed, success rate for translation novel anti-infectives into clinic. Besides bacterial killing, host viability barrier function appear as relevant but seldomly measured readouts. Moreover, virulence factors signaling molecules are typically not addressed in current models. Here, we describe a reproducible protocol...
Staphylococcus aureus possesses a large arsenal of immune-modulating factors, enabling it to bypass the immune system’s response. Here, we demonstrate that acid phosphatase SapS is secreted during macrophage infection and promotes its intracellular survival in this type cell. In animal models, SA564 sapS mutant demonstrated significantly lower bacterial burden liver renal tissues mice at four days post comparison wild type, along with pathogenicity zebrafish model. The elicits inflammatory...
Acute and chronic liver inflammation is driven by cytokine chemokine release from various cell types in the liver. Here, we report that induction of inflammatory mediators associated with a yet undescribed upregulation metalloproteinase ADAM8 different murine hepatitis models. We further show importance expression for production cultured cells. As model acute inflammation, investigated tissue lipopolysaccharide- (LPS-) treated mice which was markedly upregulated compared to control mice. In...
By virtue of mitochondrial control energy production, reactive oxygen species (ROS) generation, and maintenance Ca2+ homeostasis, mitochondria play an essential role in modulating T cell function. The uniporter (MCU) is the pore-forming unit main protein complex mediating uptake. Recently, MCU has been shown to modulate signals at subcellular organellar interfaces, thus fine-tuning NFAT translocation activation. mechanisms underlying this modulation whether additional subpopulation-specific...
Severe epithelial dysfunction is one major hallmark throughout the pathophysiological progress of bacterial pneumonia. Junctional and cellular adhesion molecules (e.g., JAMA-A, ICAM-1), cytokines TNFα), growth factors TGFα), controlling proper lung barrier function leukocyte recruitment, are proteolytically cleaved released into extracellular space through a disintegrin metalloproteinase (ADAM) 17. In cell-based assays, we could show that protein expression, maturation, activation ADAM17...
Chronic lung diseases (e.g. chronic obstructive pulmonary disease, cystic fibrosis) are incurable. Epithelial senescence, a state of dysfunctional cell cycle arrest, contributes to the progression such diseases. We differntiated basal cells airway (bronchial) organoids. The organoids were treated with doxorubicin (Dox), quercetin (Quer) and combination Dox Quer. Single sequencing showed that composed (transitional) basal, secretory, goblet, deuterosomal ciliated cells. In addition, we...
The ubiquitous opportunistic pathogen Pseudomonas aeruginosa is responsible for severe infections and notoriously known acquiring antimicrobial resistance. Inhibiting the bacterium’s extracellular elastase, LasB – a zinc-dependent protease presents promising strategy to mitigate its virulence. Within this medicinal chemistry–driven hit-to-lead optimization campaign, new series of highly potent dipeptidic phosphonates designed synthesized following structure–based drug discovery approach. In...
ABSTRACT Aim Periodontal disease is driven by oral pathogens, including Porphyromonas gingivalis , and the release of inflammatory cytokines. These cytokines (e.g., TNF) or their receptors IL‐1R) are substrates a disintegrin metalloproteinases (ADAMs). In this study, we aimed to determine effects ADAMs on periodontal phenotypes. Materials Methods Western blot FRET‐based activity measurements gingival crevicular fluid (GCF) patients were compared with those infected ( P. ) cytokine‐stimulated...