A5022659881- Sphingolipid Metabolism and Signaling
- Microbial Natural Products and Biosynthesis
- Cytokine Signaling Pathways and Interactions
- Pain Mechanisms and Treatments
- Venomous Animal Envenomation and Studies
- Microbial Metabolic Engineering and Bioproduction
- Genomics and Phylogenetic Studies
- Parasites and Host Interactions
- Plant-based Medicinal Research
- Nitric Oxide and Endothelin Effects
- Neuropeptides and Animal Physiology
- Immunotherapy and Immune Responses
- Phytochemical compounds biological activities
- Biosimilars and Bioanalytical Methods
- Immune Cell Function and Interaction
- interferon and immune responses
- Neuroinflammation and Neurodegeneration Mechanisms
- Marine Invertebrate Physiology and Ecology
- Rabies epidemiology and control
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Platelet Disorders and Treatments
- Lichen and fungal ecology
- Nuclear Structure and Function
- Acne and Rosacea Treatments and Effects
Fraunhofer Institute for Translational Medicine and Pharmacology
2015-2024
LOEWE Centre for Translational Biodiversity Genomics
2019-2024
Fraunhofer Institute for Molecular Biology and Applied Ecology
2015-2020
Institute of Molecular Biology
2019
Asklepios Fachkliniken München-Gauting
2015
Goethe University Frankfurt
2012-2015
Institute of Pharmacology
2010
Natural products (NPs) from microorganisms have been important sources for discovering new therapeutic and chemical entities. While their corresponding biosynthetic gene clusters (BGCs) can be easily identified by gene-sequence-similarity-based bioinformatics strategies, the actual access to these NPs structure elucidation bioactivity testing remains difficult. Deletion of encoding RNA chaperone, Hfq, results in strains losing production most NPs. By exchanging native promoter a desired BGC...
Lichen-forming fungi are symbiotic organisms that synthesize unique natural products with potential for new drug leads. Here, we explored the pharmacological activity of six lichen extracts (Evernia prunastri, Pseudevernia furfuracea, Umbilicaria pustulata, crustulosa, Flavoparmelia caperata, Platismatia glauca) in context cancer and inflammation using a comprehensive set 11 functional biochemical vitro screening assays. We assayed intracellular Ca2+ levels cell migration. For cancer,...
Lichen extracts containing, among other compounds, depsides such as evernic acid, atranorin, and lecanoric acid possess anti-proliferative effects. We aimed to identify lichen metabolites that are responsible for the observed performed cytotoxicity, cell colony, cycle apoptosis assays in various lines or primary immune cells. analyzed several proteins apoptosis-related gain insights into underlying mechanism. All reduced viability of tested (HCT-116, HEK293T, HeLa, NIH3T3, RAW246.7) a...
Ceramides are mediators of inflammatory processes. In experimental autoimmune encephalomyelitis (EAE), an animal model multiple sclerosis (MS), we observed that CerS6 mRNA expression was upregulated 15-fold in peripheral blood leukocytes before the onset EAE symptoms. from MS patients, a 3.9-fold upregulation found. Total genetic deletion and selective leucocytes exacerbated progression clinical symptoms mice. This associated with enhanced leukocyte, predominantly neutrophil infiltration...
Ceramide synthases (CerS) synthesize chain length specific ceramides (Cer), which mediate cellular processes in a length-dependent manner. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), we observed that the genetic deletion CerS2 suppresses EAE pathology by interaction with granulocyte-colony stimulating factor (G-CSF) signaling and CXC motif chemokine receptor 2 (CXCR2) expression, leading to impaired neutrophil migration. present study,...
The venom of honeybees is composed numerous peptides and proteins has been used for decades as an anti-inflammatory anti-cancer agent in traditional medicine. However, the bioactivity specific biomolecular components evaluated predominant constituent, melittin. So far, only a few melittin-like from solitary bee species have investigated, molecular mechanisms venoms therapeutic agents remain largely unknown. Here, preclinical pharmacological activities known proteo-transcriptomically...
Summary Prostacyclin synthesized at the sites of nerve injuries regulates accumulation resident macrophages. These cells express IL1β, which supports development neuropathic pain. is an important mediator peripheral pain sensation. Here, we investigated its potential participation in mediating and found that prostacyclin receptor (IP) knockout mice exhibited markedly decreased behavior. Application IP antagonist to injury site or selective deficiency myeloid mimicked antinociceptive effect...
Snakebite primarily impacts rural communities of Africa, Asia, and Latin America. The sharp-nosed viper (Deinagkistrodon acutus) is among the snakes highest medical importance in Asia. Despite various studies on its venom using modern venomics techniques, a comprehensive understanding composition function this species' remains lacking. We combined proteogenomics with extensive bioactivity profiling to present first genome-level catalogue D. acutus proteins their exochemistry. Our analysis...
The role of ventral hippocampus (vHipp) astroglial gliotransmission in depression was studied using chronic restraint stress (CRS) and unpredictable mild (CUMS) rodent models. CRS increased Cx43 hemichannel activity extracellular glutamate levels the vHipp blocking hemichannel-dependent during prevented development buildup. Moreover, acute blockade hemichannels induced antidepressant effects rats previously subjected to or CUMS. This effect by coinjection D-serine. Furthermore, decreased...
A promising new approach to broad spectrum antiviral drugs is the inhibition of eukaryotic translation initiation factor 4A (elF4A), a DEAD-box RNA helicase that effectively reduces replication several pathogenic virus types. Beside antipathogenic effect, modulation host enzyme activity could also have an impact on immune system. Therefore, we performed comprehensive study influence elF4A with natural and synthetic rocaglates various cells. The effect zotatifin, silvestrol CR-31-B (-), as...
Abstract FTY720 (fingolimod) is, after its phosphorylation by sphingosine kinase (SPHK) 2, a potent, non-selective sphingosine-1-phosphate (S1P) receptor agonist. has been shown to reduce the nociceptive behavior in paclitaxel model for chemotherapy-induced neuropathic pain through downregulation of S1P 1 (S1P1) microglia spinal cord. Here, we investigated mechanisms underlying antinociceptive effects trauma-induced pain. We found that intrathecal administration phosphorylated (FTY720-P)...
Abstract Natural products (NPs) from microorganisms have been important sources for discovering new therapeutic and chemical entities. While their corresponding biosynthetic gene clusters (BGCs) can be easily identified by gene‐sequence‐similarity‐based bioinformatics strategies, the actual access to these NPs structure elucidation bioactivity testing remains difficult. Deletion of encoding RNA chaperone, Hfq, results in strains losing production most NPs. By exchanging native promoter a...
We characterized the in vitro safety and bioavailability profile of silvestrol, a compound effective against various viruses, such as corona- Ebolaviruses, with an EC50 value about 5 nM. The cytotoxic silvestrol was assessed cancer cell lines, well mutagenic genotoxic potential Ames micronuclei tests, respectively. To identify off-target effects, we investigated whether modulates G-protein coupled receptor (GPCR) signaling pathways. predict its stability, permeability cellular uptake were...
Summary Introduction of biotherapeutics has been a major milestone in the treatment different chronic diseases. Nevertheless, immune system can recognize administered biological as non-self and respond with generation anti-drug antibodies (ADA), including neutralizing ADA (nADA). Immunogenic responses may result altered drug dynamics kinetics leading to changes safety efficacy. However, there are several challenges standard techniques for immunogenicity testing. Ustekinumab (UST), used...
Abstract Objective We investigated the impact of concomitant MTX on ustekinumab (UST) levels and antidrug antibody (ADA) formation in PsA evaluated consequences pharmacodynamics pharmacokinetics. Methods conducted a post-hoc analysis 112 serum samples subjects treated with open-label UST either (UST/MTX, n = 58) or placebo (UST/pbo, 54) obtained randomized (1:1), double-blind, multicentre trial. A validated antibody-binding-based multitiered testing was used to detect ADA neutralizing...
Abstract Background: Prostacyclin (PGI2) is known to be an important mediator of peripheral pain sensation (nociception) whereas little about its role in central sensitization. Methods: The levels the stable PGI2-metabolite 6-keto-prostaglandin F1α (6-keto-PGF1α) and prostaglandin E2 (PGE2) were measured dorsal horn with use mass spectrometry after inflammation. Expression prostanoid receptors was determined by immunohistology. Effects prostacyclin receptor (IP) activation on spinal neurons...
Blood-pressure-lowering drugs are proposed to foster SARS-CoV-2 infection by pharmacological upregulation of angiotensin-converting enzyme 2 (ACE2), the binding partner virus spike (S) protein, located on surface host cells. Conversely, it is postulated that angiotensin–renin system antagonists may prevent lung damage caused infection, reducing angiotensin II levels, which can induce permeability endothelial barrier via its interaction with AT1 receptor (AT1R). Methods: We have investigated...
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Altering metabolism immune cells attractive strategy to modify their activity during autoimmunity in MS. We investigated effect modulating fatty acid animal model MS, EAE. Alpha-methylacyl-CoA racemase (AMACR) converts R-configuration branched acids into S-configuration, thereby preparing them for β-oxidation. observed a significant, disease-dependent elevation AMACR expression monocytes and T...
Sodium bituminosulfonate is derived from naturally occurring sulphur-rich oil shale and used for the treatment of inflammatory skin disease rosacea. Major molecular players in development rosacea include release enzymes that process antimicrobial peptides which, together with reactive oxygen species (ROS) vascular endothelial growth factor (VEGF), promote pro-inflammatory processes angiogenesis. The aim this study was to address mechanism(s) underlying therapeutic benefit formulation sodium...