A5079766707- Cardiomyopathy and Myosin Studies
- Ubiquitin and proteasome pathways
- Muscle Physiology and Disorders
- Force Microscopy Techniques and Applications
- Cardiovascular Effects of Exercise
- Peptidase Inhibition and Analysis
- Autophagy in Disease and Therapy
- Histone Deacetylase Inhibitors Research
- Cancer-related gene regulation
- Molecular Junctions and Nanostructures
- Cellular transport and secretion
- Nuclear Structure and Function
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Signaling Pathways in Disease
- T-cell and B-cell Immunology
- Glycosylation and Glycoproteins Research
- RNA modifications and cancer
- Acute Myeloid Leukemia Research
- Nutrition and Health in Aging
- Cellular Mechanics and Interactions
- Galectins and Cancer Biology
- Vascular Malformations Diagnosis and Treatment
- Genetics and Neurodevelopmental Disorders
- Extracellular vesicles in disease
Medizinische Hochschule Hannover
2019-2024
Goethe University Frankfurt
2013-2017
Institute of Biochemistry
2017
TU Dresden
2016
Justus-Liebig-Universität Gießen
2016
German Centre for Cardiovascular Research
2016
University Hospital Frankfurt
2016
University of Cambridge
2015
University of Würzburg
2008-2011
Johannes Gutenberg University Mainz
2009
The family of NFAT (nuclear factor activated T-cells) transcription factors plays an important role in cytokine gene regulation. In peripheral T-cells NFATc1 and -c2 are predominantly expressed. Because different promoter poly(A) site usage as well alternative splicing events, is synthesized multiple isoforms. highly inducible NFATc1/A contains a relatively short C terminus, whereas the longer, constitutively expressed isoform NFATc1/C spans extra C-terminal peptide 246 amino acids....
Abstract Tolerance to self‐antigens expressed in peripheral organs is maintained by CD4 + CD25 Foxp3 Treg cells, which are generated as a result of thymic selection or induction. Here, we demonstrate that steady‐state migratory DCs from the skin mediated conversion draining lymph nodes mice. These displayed partially mature MHC II int CD86 CD40 hi CCR7 phenotype, used endogenous TGF‐β for and showed nuclear RelB translocation. Deficiency alternative NF‐κB signaling pathway (RelB/p52) reduced...
Autophagy is an intracellular recycling and degradation pathway that depends on membrane trafficking. Rab GTPases are central for autophagy but their regulation especially through the activity of GEFs remains largely elusive. We employed a RNAi screen simultaneously monitoring different populations autophagosomes identified 34 out 186 GTPase, GAP GEF family members as potential regulators, amongst them SMCR8. SMCR8 uses overlapping binding regions to associate with C9ORF72 or C9ORF72-ULK1...
ABSTRACT Microtubules execute diverse mitotic events that are spatially and temporally separated; the underlying regulation is poorly understood. By combining drug treatments, large-scale immunoprecipitation mass spectrometry, we report first comprehensive map of phase-specific protein interactions microtubule-end binding protein, EB1. EB1 interacts with some, but not all, its partners throughout mitosis. We show interaction Astrin-SKAP complex, a key regulator chromosome segregation,...
Ribosome biogenesis is a multistep cellular pathway that involves more than 200 regulatory components to ultimately generate translation-competent 80S ribosomes. The initial steps of this process, particularly rRNA processing, take place in the nucleolus, while later stages occur nucleoplasm and cytoplasm. One critical factor 28S maturation SUMO-isopeptidase SENP3. SENP3 tightly interacts with nucleolar scaffold protein NPM1 associated 60S preribosomes. A central question how changes energy...
Myosin II is the main force-generating motor during muscle contraction. exists as different isoforms that are involved in diverse physiological functions. One outstanding question whether myosin heavy chain (MHC) alone account for these distinct properties. Unique sets of essential and regulatory light chains (RLCs) known to assemble with specific MHCs, raising intriguing possibility contribute specialized Here, we asked RLCs this functional diversification. To end, generated chimeric motors...
Abstract Background Chemotherapy is the first line of treatment for cancer patients. However, side effects cause severe muscle atrophy or chemotherapy‐induced cachexia. Previously, NF‐κB/MuRF1‐dependent pathway was shown to induce We hypothesized that acute collateral toxic chemotherapy on muscles might involve other unknown pathways promoting atrophy. In this study, we investigated differential chemotherapeutic drugs and probed whether alternative molecular mechanisms lead Methods employed...
Reactive oxygen species generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases contribute to angiogenesis and vascular repair. NADPH oxidase organizer 1 (NoxO1) is a cytosolic protein facilitating assembly of constitutively active oxidases. We speculate that NoxO1 also contributes basal reactive formation in the system thus modulates angiogenesis.A knockout mouse was generated, studied cultured cells vivo. Angiogenesis developing retina after femoral artery ligation...
Precise assembly of the sarcomere, a force-generating unit in striated muscles, is critical for muscle contraction. Defective sarcomere organization linked to myopathies and cachexia. The molecular mechanisms concerning are poorly understood. Here, we report that SUMO-specific isopeptidase SENP3 determines by specifically regulating sarcomeric contractile myosin heavy-chain gene MyHC-II. ability mature cells severely compromised SENP3-depleted cells. Mechanistically, associated with SETD7...
Abstract Myosin family motors play diverse cellular roles. Precise insights into how the light chains contribute to functional variabilities among myosin motors, however, remain unresolved. Here, it is demonstrated that fast skeletal muscle II isoform heavy chain (MHC‐IID) can be transformed a processive motor, by simply replacing native regulatory MLC2f with variant MLC2v from slow II. Single molecule kinetic analyses and optical trapping measurements of hybrid motor reveal marked changes...
The myosin II motors are ATP-powered force-generating machines driving cardiac and muscle contraction. Myosin heavy chain isoform-beta (β-MyHC) is primarily expressed in the ventricular myocardium slow-twitch fibers, such as M. soleus. soleus-derived (SolM-II) often used an alternative to β-cardiac (βM-II); however, direct assessment of biochemical mechanical features native myosins limited. By employing optical trapping, we examined mechanochemical properties isolated from rabbit heart...
Despite recent studies on the role of ubiquitin-related SUMO modifier in cell fate decisions, our understanding precise molecular mechanisms these processes is limited. Previously, we established that isopeptidase SENP3 regulates chromatin assembly MLL1/2 histone methyltransferase complex at distinct HOX genes, including osteogenic master regulator DLX3. A comprehensive mechanism transcriptional function was not understood. Here, identified flightless-I homolog (FLII), a member gelsolin...
How various myosin isoforms fulfill the diverse physiological requirements of distinct muscle types remain unclear. Myosin II expressed in skeletal muscles determine mechanical performance specific muscles. Here, we employed a single-molecule optical trapping method and compared chemomechanical properties slow fast isoforms. Stiffness motor is key to its force-generating ability during contraction. We found that acto-myosin (AM) cross-bridge stiffness depends on nucleotide state as...
Abstract Myonecrosis is a frequent clinical manifestation of envenomings by Viperidae snakes, mainly caused the toxic actions secreted phospholipase A 2 (sPLA ) enzymes and sPLA -like homologs on skeletal muscle fibers. hallmark necrotic process induced these myotoxins rapid appearance hypercontracted fibers, attributed to massive influx Ca 2+ resulting from cell membrane damage. However, possibility having, in addition, direct effect contractile machinery fibers when internalized has not...
Summary Adverse effects of chemotherapies can outweigh the benefits in cancer patients. Various chemotherapeutics are linked to muscle wasting or cachexia, drastically reducing chance survivability Insights into molecular basis chemotherapy-induced cachexia is an unmet need improve treatment strategies. Here, we investigated tyrosine kinase inhibitor class chemotherapeutic agents for their on function. Sorafenib, but not Nilotinib and Imatinib, triggered cachexia. System-wide transcriptome...