A5062905648- Mass Spectrometry Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Advanced Proteomics Techniques and Applications
- Alzheimer's disease research and treatments
- Molecular Biology Techniques and Applications
- Computational Drug Discovery Methods
- Protein Degradation and Inhibitors
- Cholinesterase and Neurodegenerative Diseases
- Neuroscience and Neuropharmacology Research
- Analytical Chemistry and Chromatography
- Neuroinflammation and Neurodegeneration Mechanisms
- Mitochondrial Function and Pathology
- Nuclear Physics and Applications
- Ubiquitin and proteasome pathways
- Histone Deacetylase Inhibitors Research
- Protein Structure and Dynamics
- Ion channel regulation and function
- Metabolism and Genetic Disorders
- Spectroscopy Techniques in Biomedical and Chemical Research
- Drug Transport and Resistance Mechanisms
- Liver Disease Diagnosis and Treatment
- Ion Transport and Channel Regulation
- Immune cells in cancer
- Microfluidic and Capillary Electrophoresis Applications
- Bacterial Identification and Susceptibility Testing
Heidelberg University
2016-2025
Mannheim University of Applied Sciences
2016-2025
University Hospital Heidelberg
2021-2025
Bernstein Center for Computational Neuroscience Heidelberg-Mannheim
2022-2025
Heidelberg University
2023-2024
University Medical Centre Mannheim
2022-2024
GlaxoSmithKline (Germany)
2017
Ludwig-Maximilians-Universität München
2009
Center for Integrated Protein Science Munich
2009
Roche (Switzerland)
2009
Aryl hydrocarbon receptor (AHR) activation by tryptophan (Trp) catabolites enhances tumor malignancy and suppresses anti-tumor immunity. The context specificity of AHR target genes has so far impeded systematic investigation activity its upstream enzymes across human cancers. A pan-tissue signature, derived natural language processing, revealed that 32 entities, interleukin-4-induced-1 (IL4I1) associates more frequently with than IDO1 or TDO2, hitherto recognized as the main Trp-catabolic...
Abstract The dynamics and phenotypes of intratumoral myeloid cells during tumor progression are poorly understood. Here we define cellular states in gliomas by longitudinal single-cell profiling demonstrate their strict control the genotype: isocitrate dehydrogenase (IDH)-mutant tumors, differentiation infiltrating is blocked, resulting an immature phenotype. In late-stage gliomas, monocyte-derived macrophages drive tolerogenic alignment microenvironment, thus preventing T cell response. We...
Tankyrases 1 and 2 (TNKS1/2) are promising pharmacological biotargets with possible applications for the development of novel anticancer therapeutics. A focused structure–activity relationship study was conducted based on tankyrase inhibitor JW74 (1). Chemical analoging improved 1,2,4-triazole core led to 4-{5-[(E)-2-{4-(2-chlorophenyl)-5-[5-(methylsulfonyl)pyridin-2-yl]-4H-1,2,4-triazol-3-yl}ethenyl]-1,3,4-oxadiazol-2-yl}benzonitrile (G007-LK), a potent, "rule 5" compliant metabolically...
Solid supported probes have proven to be an efficient tool for chemical proteomics. The kinobeads technology features kinase inhibitors covalently attached Sepharose affinity enrichment of kinomes from cell or tissue lysates. This technology, combined with quantitative mass spectrometry, is particular interest the profiling inhibitors. It often leads identification new targets medicinal chemistry campaigns where it allows a two-in-one binding and selectivity assay. assay can also uncover...
A commonly used small-molecule probe in cell-signaling research is the phosphoinositide 3-kinase inhibitor LY294002. Quantitative chemoproteomic profiling shows that LY294002 and LY303511, a close analogue devoid of PI3K activity, inhibit BET bromodomain proteins BRD2, BRD3, BRD4 comprise family targets structurally unrelated to PI3K. Both compounds competitively acetyl-lysine binding first but not second cell extracts. X-ray crystallography chromen-4-one scaffold represents new...
Abstract Background Glioblastoma is the most frequent and a particularly malignant primary brain tumor with no efficacy-proven standard therapy for recurrence. It has recently been discovered that excitatory synapses of AMPA-receptor subtype form between non-malignant neurons cells. This neuron-tumor network connectivity contributed to glioma progression could be efficiently targeted EMA/FDA approved antiepileptic AMPA receptor inhibitor perampanel in preclinical studies. The PerSurge trial...
Neuronal activity regulated pentraxin (Narp) has been implicated in the aggregation of AMPA-type glutamate receptors (GluR) at excitatory synapses. In present paper, we examine role endogenous Narp synapse formation by using novel, dominant-negative mutants (dnNarp) that selectively bind and prevent its accumulation Axons from neurons transfected with wild-type showed an increase their ability to cluster AMPA on spinal neurons, whereas axons dnNarp a marked decrease induce GluR1 clusters...
Most kinase inhibitor drugs target the binding site of nucleotide cosubstrate ATP. The high intracellular concentration ATP can strongly affect potency and selectivity depending on affinity for Here we used a defined chemoproteomics system based competition-binding assays in cell extracts from Jurkat SK-MEL-28 cells with immobilized mimetics (kinobeads). This enabled us to assess affinities more than 200 kinases cellular cofactors ATP, ADP, GTP effects divalent metal ions Mg(2+) Mn(2+)....
To facilitate the transition of MALDI-MS Imaging (MALDI-MSI) from basic science to clinical application, it is necessary analyze formalin-fixed paraffin-embedded (FFPE) tissues. The aim improve in situ tryptic digestion for MALDI-MSI FFPE samples and determine if similar results would be reproducible obtained different sites.
Abstract Metabolites, lipids, and other small molecules are key constituents of tissues supporting cellular programs in health disease. Here, we present METASPACE, a community-populated knowledge base spatial metabolomes from imaging mass spectrometry data. METASPACE is enabled by high-performance engine for metabolite annotation confidence-controlled way that makes results comparable between experiments laboratories. By sharing their publicly, users continuously populate annotated currently...
Abstract Pathological microglia activation can promote neuroinflammation in many neurodegenerative diseases, and it has therefore emerged as a potential therapeutic target. Increasing evidence suggests alterations lipid metabolism modulators indicators its effector functions. Yet, how dynamics activated is affected by inflammatory stimuli demands additional investigation to allow development of more effective therapies. Here, we report an extensive matrix-assisted laser desorption/ionization...
The development of miniaturized high-throughput in situ screening platforms capable handling the entire process drug synthesis to final is essential for advancing discovery future. In this study, an approach based on combinatorial solid-phase synthesis, enabling efficient libraries proteolysis targeting chimeras (PROTACs) array format presented. This on-chip platform allows direct biological without need transfer steps. UV-induced release target molecules into individual droplets facilitates...