A5107972901- Autophagy in Disease and Therapy
- Cardiomyopathy and Myosin Studies
- Genetics, Aging, and Longevity in Model Organisms
- Hepatitis C virus research
- Congenital Diaphragmatic Hernia Studies
- Neonatal Respiratory Health Research
- Renal Diseases and Glomerulopathies
- Neuroscience of respiration and sleep
- RNA modifications and cancer
- Muscle Physiology and Disorders
- Cell Adhesion Molecules Research
- Synthesis and Reactivity of Heterocycles
- Protein Degradation and Inhibitors
- Amyotrophic Lateral Sclerosis Research
- Axon Guidance and Neuronal Signaling
- Renal and related cancers
- Hereditary Neurological Disorders
- Tissue Engineering and Regenerative Medicine
- Nitric Oxide and Endothelin Effects
- Cancer-related Molecular Pathways
- Metabolomics and Mass Spectrometry Studies
- Peptidase Inhibition and Analysis
- Cannabis and Cannabinoid Research
- Gene expression and cancer classification
- Social Robot Interaction and HRI
Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
2016-2024
University of Cologne
2019-2024
Medizinische Hochschule Hannover
2018
University Medical Center Freiburg
1997-2017
Max Planck Institute for Heart and Lung Research
2011-2017
University of Freiburg
2010-2017
Institute of Genetics
2016
IL-33 is a tissue-derived cytokine that induces and amplifies eosinophilic inflammation has emerged as promising new drug target for asthma allergic disease. Common variants at IL33 IL1RL1, encoding the receptor ST2, associate with eosinophil counts asthma. Through whole-genome sequencing imputation into Icelandic population, we found rare variant in (NM_001199640:exon7:c.487-1G>C (rs146597587-C), allele frequency = 0.65%) disrupts canonical splice acceptor site before last coding exon. It...
Ageing is driven by a loss of cellular integrity
Abstract Autophagy provides nutrients during starvation and eliminates detrimental cellular components. However, accumulating evidence indicates that autophagy is not merely a housekeeping process. Here, by combining mouse models of neuron‐specific ATG5 deficiency in either excitatory or inhibitory neurons with quantitative proteomics, high‐content microscopy, live‐imaging approaches, we show protein functions to regulate cAMP‐dependent kinase A (PKA)‐mediated phosphorylation...
Severe tissue injury results in early activation of serine protease systems including the coagulation and complement cascade. In this context, little is known about factor VII-activating (FSAP), which activated by substances released from damaged cells such as histones nucleosomes. Therefore, we have measured FSAP trauma patients identified novel substrates human plasma. Mass spectrometry-based methods were used to identify binding proteins Anaphylatoxin generation was ELISA, Western...
Enlarged vestibular aqueduct (EVA) is one of the most commonly identified inner ear malformations in hearing loss patients including Pendred syndrome. While biallelic mutations SLC26A4 gene, encoding pendrin, causes non-syndromic with EVA or syndrome, a considerable number appear to carry mono-allelic mutation. This suggests faulty pendrin regulatory machinery results loss. Here we identify EPHA2 as another causative gene syndrome SLC26A4. EphA2 forms protein complex controlling...
Genetic diseases constitute the most important cause for end-stage renal disease in children and adolescents. Mutations ACTN4 gene, encoding actin-binding protein α-actinin-4, are a rare of autosomal dominant familial focal segmental glomerulosclerosis (FSGS). Here, we report identification novel, disease-causing mutation (p.G195D, de novo) sporadic case childhood FSGS using next generation sequencing. Proteome analysis by quantitative mass spectrometry (MS) patient-derived urinary...
Background . Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of premature birth, characterized by impaired alveolar development and inflammation. Pathomechanisms contributing to BPD are poorly understood. However, it assumed that genetic factors predispose other pulmonary diseases preterm neonates, such as neonatal respiratory distress syndrome (RDS). For association studies, genes upregulated during alveolarization major candidates for analysis, example, matrix...
Diseases of the kidney filtration barrier are a leading cause ESRD. Most disorders affect podocytes, polarized cells with limited capacity for self-renewal that require tightly controlled signaling to maintain their integrity, viability, and function. Here, we provide an atlas in vivo phosphorylated, glomerulus-expressed proteins, including podocyte-specific gene products, identified unbiased tandem mass spectrometry-based approach. We discovered 2449 phosphorylated proteins corresponding...
The emergence of multi-drug resistant bacteria threatens to end the era antibiotics. Drug have evolved mechanisms overcome antibiotics at therapeutic doses and further dose increases are not possible due systemic toxicity. Here we present a pilot study ex vivo lung perfusion (EVLP) with high antibiotic therapy followed by autotransplantation as new last resort for otherwise incurable multidrug infections. Severe Pseudomonas aeruginosa pneumonia was induced in lower left lungs (LLL) 18...
Bronchopulmonary dysplasia (BPD) is the chronic lung disease of preterm infants and still represents a major burden prematurity. Several clinical risk factors for onset are already known. In addition, some candidate genes have recently been identified. We set out to determine as well genetic development BPD in German population. 155 born with gestational age ࣘ 28 at tertiary neonatal Centre, Freiburg, were recruited. Clinical data recorded from hospital charts. 47 children developed moderate...
The Ras Association Domain Family (RASSF) encodes members of tumor suppressor genes which are frequently inactivated in human cancers. Here, the function and regulation RASSF10, that contains a RA (Ras-association) two coiled domains, was investigated. We utilized mass spectrometry immuno-precipitation to identify interaction partners RASSF10. Additionally, we analyzed up- downstream pathways RASSF10 involved its suppressive function. report binds ASPP1 (Apoptosis-stimulating protein p53)...
Satellite cells (SCs) represent a distinct population of stem cells, essential for maintenance, growth and regeneration adult skeletal muscle. SCs are mononuclear located between the basal lamina plasma membrane myofibers. They typically characterized by presence transcription factor paired-box 7 (PAX7) that is widely used as satellite cell marker. Under normal physiological conditions quiescent but activated insults such injury, disease or exercise. Once activated, proliferate subsequently...
Rationale: Cardiac fibroblasts are activated following myocardial infarction (MI) and cardiac fibrosis is a major driver of the growing burden heart failure. A non-invasive targeting method for would be advantageous because their importance imaging therapy. Methods: Targeting was achieved by linking 7-amino acid peptide (EP9) to perfluorocarbon-containing nanoemulsion (PFC-NE) visualization 19F-combined with 1H-MRI. In vivo ex 1H/19F MRI performed on Bruker 9.4 T AVANCE III wide-bore nuclear...
The administration of labeled amino acids has become the preferred method to measure dynamics protein turnover in living animals. Stable isotopes have been used as tracers explore acid flux different metabolic pathways. Recently, stable isotope labeling cell culture (SILAC), monitor individual rates and intact This is based on incorporation essential resulting appearance end products that can be quantified by mass spectrometry. We performed an pulsed SILAC mice calculate via rate post...
Abstract Mislocalization of the predominantly nuclear RNA/DNA binding protein, TDP-43, occurs in motor neurons ~95% ALS patients, but contribution axonal TDP-43 to this fatal neurodegenerative disease is unclear. Here, we find accumulation axons intra-muscular nerves from and neuromuscular junctions (NMJs) a mouse model with mislocalization. This leads formation G3BP1- TDP-43- positive RNA-granules neuron axons, inhibition local protein synthesis NMJs. Specifically, synaptic levels...
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