A5090009576- Pain Mechanisms and Treatments
- Cancer, Hypoxia, and Metabolism
- Ion Channels and Receptors
- Ion channel regulation and function
- ATP Synthase and ATPases Research
- Neuropeptides and Animal Physiology
- DNA Repair Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Mitochondrial Function and Pathology
- Neurobiology and Insect Physiology Research
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Neuroscience and Neuropharmacology Research
- Nicotinic Acetylcholine Receptors Study
- Venomous Animal Envenomation and Studies
- Pharmacological Effects of Natural Compounds
- Cancer-related Molecular Pathways
- Gene Regulatory Network Analysis
- BRCA gene mutations in cancer
- RNA Research and Splicing
- Receptor Mechanisms and Signaling
- Anesthesia and Neurotoxicity Research
- Cancer Treatment and Pharmacology
- Traumatic Brain Injury and Neurovascular Disturbances
- Myofascial pain diagnosis and treatment
University of Cologne
2016-2024
University Hospital Cologne
2014-2024
Klinik und Poliklinik für Psychosomatik und Psychotherapie
2020
Poliklinik für Endokrinologie, Diabetologie und Präventivmedizin
2012-2020
Max Planck Institute for Molecular Genetics
2006-2017
Centrum für Integrierte Onkologie
2012
Max Planck Society
2006-2010
Charité - Universitätsmedizin Berlin
2007
University of California, San Francisco
2005
The epsilon isoform of protein kinase C (PKCepsilon) has emerged as a critical second messenger in sensitization toward mechanical stimulation models neuropathic (diabetes, alcoholism, and cancer therapy) well acute chronic inflammatory pain. Signaling pathways leading to activation PKCepsilon remain unknown. Recent results indicate signaling from cAMP PKC. A mechanism connecting PKC, two ubiquitous, commonly considered separate pathways, remains elusive. We found that, cultured DRG neurons,...
Background TRPV4 and the cellular cytoskeleton have each been reported to influence mechanosensitive processes as well development of mechanical hyperalgesia. If how interacts with microtubule actin at a molecular functional level is not known. Methodology Principal Findings We investigated interaction cytoskeletal components biochemically, cell biologically by observing morphological changes DRG-neurons DRG-neuron-derived F-11 cells, functionally calcium imaging. find that physically...
The composition of tumor-infiltrating lymphocytes (TIL) reflects biology and immunogenicity cancer. Here, we characterize T-cell subsets expression immune checkpoint molecules in head neck squamous cell carcinoma (HNSCC). We analyzed TIL primary tumors (n = 34), blood (peripheral mononuclear cells (PBMC); n 34) non-cancerous mucosa 7) 34 treatment-naïve HNSCC patients PBMC 15 healthy controls. Flow cytometry analyses revealed a highly variable infiltration mainly an effector memory phenotype...
Abstract Venoms have evolved >100 times in all major animal groups, and their components, known as toxins, been fine-tuned over millions of years into highly effective biochemical weapons. There are many outstanding questions on the evolution toxin arsenals, such how venom genes originate, contributes to fitness venomous species, which modifications at genomic, transcriptomic, protein level drive evolution. These received particularly little attention outside snakes, cone snails,...
Paralogs for several proteins implicated in neurodegenerative disorders have been identified and explored to further facilitate the identification of molecular mechanisms contributing disease pathogenesis. For disease-causing protein spinocerebellar ataxia type 2, ataxin-2, a paralog unknown function, termed ataxin-2-like, has described. We discovered that ataxin-2-like associates with known interaction partners RNA helicase DDX6 poly(A)-binding protein, ataxin-2 itself. Furthermore, we...
The antimetabolite 5-fluorouracil is a widely used chemotherapeutic for the treatment of several solid cancers. However, resistance to remains major drawback in its clinical use. In this study we report that HeLa cells with resulted de novo assembly stress granules. Moreover, revealed granule under conditions as well disassembly altered treated 5-fluorouracil. Notably, discovered RACK1, protein mediating cell survival and apoptosis, component 5-fluorouracil-induced To explore mode action...
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...
Abstract Protein kinase C epsilon (PKCε) is an important intracellular signaling molecule in primary afferent nociceptors, implicated acute and chronic inflammatory as well neuropathic pain. In behavioral experiments mediators produce PKCε‐dependent hyperalgesia only male rats. The mechanism underlying this sexual dimorphism unknown. We show that the hormone environment of female rats changes nociceptive peripheral sensory neuron. This change maintained culture also absence a...
Abstract We evaluated the signalling pathway by which estrogen acts in peripheral tissue to produce protein kinase Cɛ (PKCɛ)‐dependent mechanical hyperalgesia. Specific agonists for classical receptors (ER), ERα and ERβ, did not result activation of PKCɛ neurons dissociated rat dorsal root ganglia. In contrast, G‐1, a specific agonist recently identified G‐protein‐coupled receptor, GPR30, induced translocation. Involvement GPR30 independence ERβ was confirmed using simultaneous antagonist...
Recently, we described estrogen and agonists of the G-protein coupled receptor GPR30 to induce protein kinase C (PKC)ε-dependent pain sensitization. PKCε phosphorylates ion channel transient potential, vanilloid subclass I (TRPV1) close a novel microtubule-TRPV1 binding site. We now modeled tubulin TRPV1 C-terminus. The model suggests phosphorylation TRPV1-S800 abolish tubulin-TRPV1 interaction. Indeed, in vitro hindered tubulin-binding TRPV1. In vivo, treatment sensory neurons F-11 cells...
The voltage-gated Na + channel v 1.7 controls the balance of pain-promoting and pain-relieving receptor input.
The cellular response to heat stress is an ancient and evolutionarily highly conserved defence mechanism characterised by the transcriptional up-regulation of cyto-protective genes a partial inhibition splicing. These features closely resemble proteotoxic during tumor development. bromodomain protein BRD4 has been identified as integral member oxidative well inflammatory response, mainly due its role in regulation process. In addition, there are also several lines evidence implicating...
Functional cell-to-cell variability is ubiquitous in multicellular organisms as well bacterial populations. Even genetically identical cells of the same cell type can respond differently to stimuli. Methods have been developed analyse heterogeneous populations, e.g., mixture models and stochastic population models. The available methods are, however, either incapable simultaneously analysing different experimental conditions or are computationally demanding difficult apply. Furthermore, they...
Type II isoforms of cyclic adenosine monophosphate (cAMP)–dependent protein kinase A (PKA-II) contain a phosphorylatable epitope within the inhibitory domain RII subunits (pRII) with still unclear function. In vitro, phosphorylation occurs in absence cAMP, whereas staining cells pRII-specific antibodies revealed cAMP-dependent pattern. sensory neurons, we found that increased pRII immunoreactivity reflects accessibility already phosphorylated during cAMP-induced opening tetrameric RII2:C2...
Protein-protein interaction inhibitor of the sodium NaV1.7 channel has analgesic effects in preclinical models pain.
Electrophysiological studies demonstrate that transient receptor potential vanilloid subtype 1 (TRPV1) is involved in neuronal transmission. Although it expressed the peripheral as well central nervous system, questions remain whether TRPV1 present synaptic structures and processes. In study we gathered evidence can be detected spines of cortical neurons, colocalizes with both pre- postsynaptic proteins, regulates spine morphology. Moreover, also biochemically prepared synaptosomes...
Growth factors such as nerve growth factor and glial cell line-derived neurotrophic are known to induce pain sensitization. However, a plethora of other is released during inflammation tissue regeneration, many them essential for wound healing. Which wound-healing also alter the sensitivity nociceptive neurons not well known. We studied factor, basic fibroblast (bFGF), its role in Reverse transcription polymerase chain reaction showed that receptor bFGF, FGFR1, expressed lumbar rat dorsal...
Abstract Transient receptor potential vanilloid subtype 1 (TRPV1), a non‐selective cation channel, is present endogenously in dorsal root ganglia (DRG) neurons. It involved the recognition of various pain producing physical and chemical stimuli. In this work, we demonstrate that expression TRPV1 induces neurite‐like structures filopodia expressed protein localized at filopodial tips. Exogenous both DRG neuron‐derived F11 cells non‐neuronal cells, such as HeLa human embryonic kidney (HEK)...
Abstract Previously, we reported that TRPV1, the vanilloid receptor, interacts with soluble αβ‐tubulin dimers as well microtubules via its C‐terminal cytoplasmic domain. The interacting region of however, has not been defined. We found TRPV1 C‐terminus preferably β‐tubulin and less α‐tubulin. Using a systematic deletion approach biotinylated‐peptides identified two tubulin‐binding sites present in TRPV1. These sequence stretches are highly conserved all known mammalian orthologues partially...