A5057858978- Advanced Proteomics Techniques and Applications
- Bioinformatics and Genomic Networks
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Gene expression and cancer classification
- Cancer, Hypoxia, and Metabolism
- Metabolomics and Mass Spectrometry Studies
- Pancreatic and Hepatic Oncology Research
- Genetics, Bioinformatics, and Biomedical Research
- Cancer Genomics and Diagnostics
- Multiple Myeloma Research and Treatments
- SARS-CoV-2 and COVID-19 Research
- Pancreatic function and diabetes
- Mass Spectrometry Techniques and Applications
- 3D Printing in Biomedical Research
- Histone Deacetylase Inhibitors Research
- Metabolism, Diabetes, and Cancer
- Monoclonal and Polyclonal Antibodies Research
- Chemical Reactions and Isotopes
- Cancer-related Molecular Pathways
- Peptidase Inhibition and Analysis
- Ferroptosis and cancer prognosis
- PI3K/AKT/mTOR signaling in cancer
- Ion channel regulation and function
- FOXO transcription factor regulation
Technical University of Munich
2015-2024
AstraZeneca (United States)
2022-2024
ID Genomics (United States)
2024
Deutschen Konsortium für Translationale Krebsforschung
2015-2023
Leibniz-Institute for Food Systems Biology at the Technical University of Munich
2022
German Cancer Research Center
2015-2021
Heidelberg University
2015-2021
Kinase inhibitors are important cancer therapeutics. Polypharmacology is commonly observed, requiring thorough target deconvolution to understand drug mechanism of action. Using chemical proteomics, we analyzed the spectrum 243 clinically evaluated kinase drugs. The data revealed previously unknown targets for established drugs, offered a perspective on "druggable" kinome, highlighted (non)kinase off-targets, and suggested potential therapeutic applications. Integration phosphoproteomic...
Article18 February 2019Open Access Transparent process A deep proteome and transcriptome abundance atlas of 29 healthy human tissues Dongxue Wang orcid.org/0000-0002-4402-0690 Chair Proteomics Bioanalytics, Technische Universität München, Freising, Germany Search for more papers by this author Basak Eraslan Computational Biology, Department Informatics, Technical University Munich, Garching bei Biochemistry, Quantitative Biosciences Gene Center, Ludwig Maximilian Universität, Thomas Wieland...
Isobaric stable isotope labeling using, for example, tandem mass tags (TMTs) is increasingly being applied large-scale proteomic studies. Experiments focusing on proteoform analysis in drug time course or perturbation studies large patient cohorts greatly benefit from the reproducible quantification of single peptides across samples. However, such often require hundreds micrograms that cost reagents represents a major contribution to overall an experiment. Here, we describe and evaluate...
Abstract Nano-flow liquid chromatography tandem mass spectrometry (nano-flow LC–MS/MS) is the mainstay in proteome research because of its excellent sensitivity but often comes at expense robustness. Here we show that micro-flow LC–MS/MS using a 1 × 150 mm column shows reproducibility chromatographic retention time (<0.3% coefficient variation, CV) and protein quantification (<7.5% data from >2000 samples human cell lines, tissues body fluids. Deep analysis identifies >9000...
Abstract ProteomicsDB (https://www.ProteomicsDB.org) started as a protein-centric in-memory database for the exploration of large collections quantitative mass spectrometry-based proteomics data. The data types and contents grew over time to include RNA-Seq expression data, drug-target interactions cell line viability In this manuscript, we summarize new developments since previous update that was published in Nucleic Acids Research 2017. Over past two years, have enriched content by...
Although most cancer drugs modulate the activities of cellular pathways by changing posttranslational modifications (PTMs), little is known regarding extent and time- dose-response characteristics drug-regulated PTMs. In this work, we introduce a proteomic assay called decryptM that quantifies drug-PTM modulation for thousands PTMs in cells to shed light on target engagement drug mechanism action. Examples range from detecting DNA damage chemotherapeutics, identifying drug-specific PTM...
The coordination of protein synthesis and degradation regulating abundance is a fundamental process in cellular homeostasis. Today, mass spectrometry-based technologies allow determination endogenous turnover on proteome-wide scale. However, standard dynamic SILAC (Stable Isotope Labeling Cell Culture) approaches can suffer from missing data across pulse time-points limiting the accuracy such analysis. This issue particular relevance when studying stability at level proteoforms because often...
HER2/ERBB2-overexpressing breast cancers targeted effectively by the small-molecule kinase inhibitor lapatinib frequently acquire resistance to this drug. In study, we employed explorative mass spectrometry profile proteome, kinome, and phosphoproteome changes in an established model of systematically investigate initial response subsequent reprogramming resistance. The resulting dataset, which collectively contains quantitative data for >7,800 proteins, >300 protein kinases, >15,000...
Abstract Proteome-wide measurements of protein turnover have largely ignored the impact post-translational modifications (PTMs). To address this gap, we employ stable isotope labeling and mass spectrometry to measure >120,000 peptidoforms including >33,000 phosphorylated, acetylated, ubiquitinated peptides for >9,000 native proteins. This site-resolved (SPOT) profiling discloses global site-specific differences in associated with presence or absence PTMs. While causal relationships...
Identifying the molecular mechanisms that promote optimal immune responses to coronavirus disease 2019 (COVID-19) vaccination is critical for future rational vaccine design. Here, we longitudinally profile innate and adaptive in 102 adults after first, second, third doses of mRNA or adenovirus-vectored COVID-19 vaccines. Using a multi-omics approach, identify key differences induced by ChAdOx1-S BNT162b2 correlate with antigen-specific antibody T cell reactogenicity. Unexpectedly, observe...
Integrated analysis of genomes, transcriptomes, proteomes and drug responses cancer cell lines (CCLs) is an emerging approach to uncover molecular mechanisms action. We extend this paradigm measuring proteome activity landscapes by acquiring integrating quantitative data for 10,000 proteins 55,000 phosphorylation sites (p-sites) from 125 CCLs. These are used contextualize p-sites predict sensitivity. For example, we find that Progesterone Receptor (PGR) associated with sensitivity drugs...
The complex architecture of transmembrane proteins requires quality control (QC) folding, membrane positioning, and trafficking as prerequisites for cellular homeostasis intercellular communication. However, it has remained unclear whether protein-specific QC hubs exist. Here we identify cereblon (CRBN), the target immunomodulatory drugs (IMiDs), a co-chaperone that specifically determines chaperone activity HSP90 toward by means counteracting AHA1. This function is abrogated IMiDs, which...
Manipulating molecules that impact T cell receptor (TCR) or cytokine signaling, such as the protein tyrosine phosphatase non-receptor type 2 (PTPN2), has significant potential for advancing cell-based immunotherapies. Nonetheless, it remains unclear how PTPN2 impacts activation, survival, and memory formation of cells. We find deficiency renders cells in vivo vitro less dependent on survival-promoting cytokines, interleukin (IL)-2 IL-15. Remarkably, briefly ex vivo-activated PTPN2-deficient...
Protein kinases are important mediators of intracellular signaling and reversibly activated by phosphorylation. Immobilized kinase inhibitors can be used to enrich these often low-abundance proteins, identify targets inhibitors, or probe their selectivity. It has been suggested that the binding affinity beads reflects a kinase's activation status, concept is under considerable debate. To assess merits idea, we performed series experiments including quantitative phosphoproteomics purification...
Lysine deacetylase inhibitors (KDACis) are approved drugs for cutaneous T cell lymphoma (CTCL), peripheral (PTCL), and multiple myeloma, but many aspects of their cellular mechanism action (MoA) substantial toxicity not well understood. To shed more light on how KDACis elicit responses, we systematically measured dose-dependent changes in acetylation, phosphorylation, protein expression response to 21 clinical pre-clinical KDACis. The resulting 862,000 dose-response curves revealed,...
Abstract Deubiquitylases (DUBs) are therapeutically amenable components of the ubiquitin machinery that stabilize substrate proteins. Their inhibition can destabilize oncoproteins may otherwise be undruggable. Here, we screened for DUB vulnerabilities in multiple myeloma, an incurable malignancy with dependency on proteasome system and identified OTUD6B as oncogene drives G1/S‐transition. LIN28B, a suppressor microRNA biogenesis, is specified bona fide cell cycle‐specific OTUD6B....
Abstract Genome-, transcriptome- and proteome-wide measurements provide valuable insights into how biological systems are regulated. However, even fundamental aspects relating to which human proteins exist, where they expressed in quantities not fully understood. Therefore, we have generated a systematic, quantitative deep proteome transcriptome abundance atlas from 29 paired healthy tissues the Human Protein Atlas Project representing genes by 17,615 transcripts 13,664 proteins. The...
Fluorescence-activated cell sorting (FACS) is a specialized technique to isolate specific subpopulations with high level of recovery and accuracy. However, the procedure can impact viability metabolic state cells. Here, we performed comparative study evaluated traditional high-pressure charged droplet-based microfluidic chip-based on phosphoproteomic profile different types. While sorted cells more closely resembled unsorted control group for most types tested, showed significant...
Abstract The electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), is the major transporter expressed in astrocytes. It highly sensitive for and main regulator of intracellular, extracellular, synaptic pH, thereby modulating neuronal excitability. However, despite these essential functions, molecular mechanisms underlying NBCe1‐mediated astrocytic response to extracellular pH changes are mostly unknown. Using primary mouse cortical astrocyte cultures, we investigated effect...
Abstract We longitudinally profiled immune responses in 102 adults who received BNT162b2 (Pfizer-BioNTech) or ChAdOx1-S (Oxford-AstraZeneca) as their primary vaccinations. Bloods were collected pre-vaccination, 1-7 days after the 1 st , 2 nd and 3 rd doses (BNT162b2 mRNA-1273) to assess innate early adaptive responses, ∼28 immunogenicity. Using a multi-omics approach including RNAseq, cytokine multiplex assay, proteomics, lipidomics, flow cytometry we identified key differences induced by...
<p>Figure S1. Quality of phospho(proteomic) dataset acquired. Figure S2. (Phospho)proteomic analysis lapatinib mode action in parental cells. S3. Signaling reprogramming resistance. S4. Identification pharmacologically actionable targets and phenotypes based on a breast cancer model S5. Metabolic changes resistant cell line model.</p>
<p>Proteome abundance dataset containing raw MaxQuant output.</p>