A5014361019- Muscle Physiology and Disorders
- Mitochondrial Function and Pathology
- Hippo pathway signaling and YAP/TAZ
- RNA Research and Splicing
- Adipose Tissue and Metabolism
- Ubiquitin and proteasome pathways
- Cardiomyopathy and Myosin Studies
- Microtubule and mitosis dynamics
- Advanced Proteomics Techniques and Applications
- Autophagy in Disease and Therapy
- Cell Adhesion Molecules Research
- CAR-T cell therapy research
- Neonatal Respiratory Health Research
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Cancer-related Molecular Pathways
- RNA and protein synthesis mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Muscle metabolism and nutrition
- Mass Spectrometry Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- Cellular Mechanics and Interactions
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
2016-2025
University of Cologne
2016-2025
München Klinik
2018-2025
University Hospital Cologne
2022-2024
München Klinik Harlaching
2019-2024
Institute of Genetics
2024
Düsseldorf University Hospital
2024
Martha-Maria Hospital
2024
Heinrich Heine University Düsseldorf
2024
Max Planck Institute for Heart and Lung Research
2011-2022
VSMCs respond to changes in the local environment by adjusting their phenotype from contractile synthetic, a phenomenon known as phenotypic modulation or switching. Failure of acquire and maintain plays key role number major human diseases, including arteriosclerosis. Although several regulatory circuits that control differentiation SMCs have been identified, decisive mechanisms govern remain unknown. Here, we demonstrate mouse miR-143/145 cluster, expression which is confined during...
Background— Significant evidence indicates that the failing heart is energy starved. During development of failure, capacity to utilize fatty acids, chief fuel, diminished. Identification alternate pathways for myocardial fuel oxidation could unveil novel strategies treat failure. Methods and Results— Quantitative mitochondrial proteomics was used identify metabolic derangements occur during cardiac hypertrophy failure in well-defined mouse models. As expected, amounts proteins involved acid...
The turnover of each protein in the mammalian proteome is a functionally important characteristic. Here, we employed high-resolution mass spectrometry to quantify dynamics nondividing cells. ratio externally supplied versus endogenous amino acids de novo synthesis was about 17:1. Using subsaturating SILAC labeling, obtained accurate rates 4106 proteins HeLa and 3528 C2C12 Comparison these human mouse cell lines revealed highly significant correlation orthologs thus high species conservation....
The establishment of the epigenetic mark H4K20me1 (monomethylation H4K20) by PR-Set7 during G 2 /M directly impacts S-phase progression and genome stability. However, mechanisms involved in regulation this event are not well understood. Here we show that SirT2 regulates deposition through deacetylation H4K16Ac (acetylation H4K16) determines levels H4K20me2/3 throughout cell cycle. binds deacetylates at K90, modulating its chromatin localization. Consistently, depletion significantly reduces...
The development of modern high-throughput instrumentation and improved core facility infrastructures leads to an accumulation large amounts scientific data. However, for a majority scientists the comprehensive analysis visualization their data goes beyond expertise. To reduce this hurdle, we developed software suite called Instant Clue that helps visually analyze gain insights into biological processes from high-dimensional dataset. combines power visual statistical analytics using straight...
Receptor interacting protein kinase 1 (RIPK1) regulates cell death and inflammatory responses downstream of TNFR1 other receptors, has been implicated in the pathogenesis degenerative diseases. RIPK1 activity induces apoptosis necroptosis, however mechanisms phosphorylation events regulating RIPK1-dependent signaling remain poorly understood. Here we show that autophosphorylation at serine 166 plays a critical role for activation kinase-dependent necroptosis. Moreover, S166 is required...
Impaired or excessive growth of endothelial cells contributes to several diseases. However, the functional involvement regulatory long non-coding RNAs in these processes is not well defined. Here, we show that antisense transcript GATA6 (GATA6-AS) interacts with epigenetic regulator LOXL2 regulate gene expression via changes histone methylation. Using RNA deep sequencing, find GATA6-AS upregulated during hypoxia. Silencing diminishes TGF-β2-induced endothelial-mesenchymal transition vitro...
The NAD + precursor nicotinamide improves diastolic dysfunction caused by aging, hypertension, or metabolic syndrome in rodents.
Mislocalization of the predominantly nuclear RNA/DNA binding protein, TDP-43, occurs in motor neurons ~95% amyotrophic lateral sclerosis (ALS) patients, but contribution axonal TDP-43 to this neurodegenerative disease is unclear. Here, we show accumulation intra-muscular nerves from ALS patients and axons human iPSC-derived patient, as well neuromuscular junctions (NMJs) a mislocalization mouse model. In axons, hyper-phosphorylated promotes G3BP1-positive ribonucleoprotein (RNP) condensate...
The insulin signaling pathway is of pivotal importance in metabolic diseases, such as diabetes, and cellular processes, aging. Insulin activates a tyrosine phosphorylation cascade that branches to create complex network affecting multiple biological processes. To understand the full spectrum cascade, we have defined tyrosine-phosphoproteome pathway, using high resolution mass spectrometry combination with phosphotyrosine immunoprecipitation stable isotope labeling by amino acids cell culture...
Myocardial diastolic stiffness and cardiomyocyte passive force (F(passive)) depend in part on titin isoform composition phosphorylation. Ca(2+)/calmodulin-dependent protein kinase-II (CaMKII) phosphorylates ion channels, Ca(2+)-handling proteins, chromatin-modifying enzymes the heart, but has not been known to target titin.To elucidate whether CaMKII modulates F(passive) normal failing myocardium.Titin phosphorylation was assessed CaMKIIδ/γ double-knockout (DKO) mouse, transgenic...
Caveolae are specialized compartments of the plasma membrane that involved in signaling, endocytosis, and cholesterol transport. Their formation requires transport caveolin-1 to membrane, but molecular mechanisms regulating largely unknown. Here, we identify a critical role for adhesion-mediated signaling through β1 integrins integrin-linked kinase (ILK) caveolae formation. Mice lacking or ILK keratinocytes have dramatically reduced numbers vivo, which is due impaired caveolin-1-containing...
Inflammation is a major factor in heart disease. IκB kinase (IKK) and its downstream target NF-κB are regulators of inflammation activated cardiac disorders, but their precise contributions targets unclear. We analyzed IKK/NF-κB function the by gain-of-function approach, generating an inducible transgenic mouse model with cardiomyocyte-specific expression constitutively active IKK2. In adult animals, IKK2 activation led to inflammatory dilated cardiomyopathy failure. Transgenic hearts showed...
Cardiomyocyte proteostasis is mediated by the ubiquitin/proteasome system (UPS) and autophagy/lysosome fundamental for cardiac adaptation to both physiologic (e.g., exercise) pathologic pressure overload) stresses. Both UPS exhibit reduced efficiency as a consequence of aging, dysfunction in these systems associated with cardiomyopathies. The muscle-specific ubiquitin ligase atrogin-1 targets signaling proteins involved hypertrophy degradation. Here, using KO mice combination vivo pulsed...