A5007912668- CAR-T cell therapy research
- Asthma and respiratory diseases
- Biomedical Ethics and Regulation
- IL-33, ST2, and ILC Pathways
- T-cell and B-cell Immunology
- Single-cell and spatial transcriptomics
- Allergic Rhinitis and Sensitization
- Immune Cell Function and Interaction
- Immunotoxicology and immune responses
- Inhalation and Respiratory Drug Delivery
- Mast cells and histamine
- Lung Cancer Diagnosis and Treatment
- 3D Printing in Biomedical Research
- Respiratory and Cough-Related Research
- Cancer-related molecular mechanisms research
- COVID-19 diagnosis using AI
- Cancer Cells and Metastasis
- Computational Drug Discovery Methods
- Biosimilars and Bioanalytical Methods
- Immune Response and Inflammation
- Virus-based gene therapy research
- Pharmacogenetics and Drug Metabolism
- Influenza Virus Research Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cell Image Analysis Techniques
Fraunhofer Institute for Toxicology and Experimental Medicine
2016-2024
German Center for Lung Research
2017-2024
Fraunhofer Society
2021
Helmholtz Zentrum München
2017
Long non-coding RNAs (lncRNAs) have potential as novel therapeutic targets in cardiovascular diseases, but detailed information about the intercellular lncRNA shuttling mechanisms heart is lacking. Here, we report an important crosstalk between cardiomyocytes and fibroblasts mediated by transfer of lncRNA-enriched extracellular vesicles (EVs) context cardiac ischemia. profiling identified two hypoxia-sensitive lncRNAs: ENSMUST00000122745 was predominantly found small EVs, whereas Neat1...
Drug-induced hepatotoxicity constitutes a major reason for non-approval and post-marketing withdrawal of pharmaceuticals. In many cases, preclinical models lack predictive capacity hepatic damage in humans. A vital concern is the integration immune system effects safety assessment. The immune-related Adverse Outcome Pathway (irAOP) approach, which applied within Immune Safety Avatar (imSAVAR) consortium, presents novel method to understand predict immune-mediated adverse events elicited by...
Abstract Background Asthma is a heterogeneous chronic disease with different phenotypes and treatment responses. Thus, there high clinical need for molecular biomarkers to aid in differentiating these distinct phenotypes. As Micro RNA s (mi s), that regulate gene expression at the post‐transcriptional level, are altered experimental human asthma, circulating mi attractive candidates identification of novel biomarkers. This study aimed identify plasmatic ‐based through translational approach....
Respiratory diseases in their broad diversity need appropriate model systems to understand the underlying mechanisms and enable development of new therapeutics. Additionally, registration substances requires risk assessment with adequate testing avoid individuals being harmed, for example, working environment. Such assessments are usually conducted animal studies. In view 3Rs principle public skepticism against experiments, human alternative methods, such as precision-cut lung slices (PCLS),...
This work focuses on the need for modeling and predicting adverse outcomes in immunotoxicology to improve nonclinical assessments of safety immunomodulatory therapies. The integrated approach includes, first, outcome pathway concept established toxicology field, and, second, systems medicine disease map describing molecular mechanisms involved a particular pathology. proposed workflow is illustrated with chimeric antigen receptor (CAR) T cell treatment as use case. To this end, linear (AOP)...
Subgroups of patients with severe asthma are insensitive to inhaled corticosteroids and require novel therapies on top standard medical care. IL-13 is considered one the key cytokines in pathogenesis, however, effect was mostly studied rodents. This study aimed assess human lung tissue for development targeted therapy approaches such as inhibition soluble or its receptor IL-4Rα subunit. Precision-cut slices (PCLS) were prepared from lungs rodents, non-human primates (NHP) humans. Direct...
Recombinant human IL-2 has been used to treat inflammatory diseases and cancer; however, side effects like skin rashes limit the use of this therapeutic. To identify key molecules cells inducing effect, we characterized IL-2-induced cutaneous immune reactions investigated relevance CD25 (IL-2 receptor α) in process. We injected intradermally into WT mice observed increases cell subsets with preferential frequencies IL-4- IL-13-producing group 2 innate lymphoid IL-17-producing dermal γδ T...
Background With increasing clinical use of NK-92 cells and their CAR-modified derivatives in cancer immunotherapy, there is a growing demand for efficient production processes these “off-the-shelf” therapeutics. In order to ensure safety prevent the occurrence secondary tumors, (CAR-)NK-92 cell proliferation has be inactivated before transfusion. This commonly achieved by gamma irradiation. Recently, we showed proof concept that low energy electron irradiation (LEEI) new method inactivation....
Abstract Background The coordinated transcriptional regulation of activated T-cells is based on a complex dynamic behavior signaling networks. Given an external stimulus, T-cell gene expression characterized by impulse and sustained patterns over the course. Here, we analyze temporal pattern activation across different populations to develop consensus signatures for activation. Results identify verify general biomarker robustly evaluating in time-resolved manner. We profiles comprising 521...
The cellular serine protease TMPRSS2, a member of the type II transmembrane (TTSP) family, cleaves and activates hemagglutinin influenza A viruses (FLUAV) in cell culture is essential for spread diverse FLUAV mice. Non-human primates (NHP), particular rhesus cynomolgus macaques, serve as animal models experimental infection common marmosets has recently also been reported. However, it currently unknown whether NHP orthologues human TMPRSS2 cleave activate contribute to viral respiratory...
Respiratory diseases in their broad diversity need appropriate model systems to understand the underlying mechanisms and enable development of new therapeutics. Additionally, registration substances requires risk assessment with adequate testing avoid individuals being harmed, for example, working environment. Such assessments are usually conducted animal studies. In view 3Rs principle public skepticism against experiments, human alternative methods, such as precision-cut lung slices (PCLS),...
Abstract Background Aging is associated with an increased incidence and mortality of Pseudomonas aeruginosa -induced pneumonias. This might be partly due to age-dependent increases in inflammatory mediators, referred as inflamm-aging a decline immune functions, known immunosenescence. Still, the impact dysregulated responses on lung infection during aging poorly understood. Here, we aimed mimic using ex vivo precision-cut slices (PCLS) neutrophils – important effector cells innate immunity...
We address the need for modelling and predicting adverse outcomes in immunotoxicology to improve non-clinical assessments of immunomodulatory therapy safety efficacy. The integrated approach includes, first, outcome pathway concept established toxicology field, and, second, systems medicine disease map describing molecular mechanisms involved a particular pathology. proposed workflow is demonstrated with CAR T cell treatment as use case. To this end, linear (AOP) expanded into interaction...
Background The coordinated transcriptional regulation of activated T-cells is based on the complex dynamic behavior signaling networks. Given an external stimulus, T-cell gene expression characterized by impulse and sustained patterns over course. Here, we analyzed temporal pattern activation across different populations to develop consensus signatures for activation. Methods We applied a meta-analysis anti-CD3/CD28 induced CD4+ kinetics publicly available transcriptomewide time series using...