A5069356732- PARP inhibition in cancer therapy
- Biosimilars and Bioanalytical Methods
- Advanced Proteomics Techniques and Applications
- Health Systems, Economic Evaluations, Quality of Life
- Mass Spectrometry Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Epigenetics and DNA Methylation
- Immunotherapy and Immune Responses
- Protein Kinase Regulation and GTPase Signaling
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Cell Adhesion Molecules Research
- Analytical Chemistry and Chromatography
- Cancer-related molecular mechanisms research
- Cellular transport and secretion
- Microtubule and mitosis dynamics
- Chemical Synthesis and Analysis
- Histone Deacetylase Inhibitors Research
- RNA and protein synthesis mechanisms
- Immune cells in cancer
- Glycosylation and Glycoproteins Research
- Prostate Cancer Treatment and Research
- Genomics and Phylogenetic Studies
- Protein Tyrosine Phosphatases
- RNA modifications and cancer
European Molecular Biology Laboratory
2013-2023
GlaxoSmithKline (Germany)
2023
European Molecular Biology Laboratory
2020
Utrecht University
2009-2013
Netherlands Metabolomics Centre
2010-2013
Cancer Genomics Centre
2009
Over the past decade peptide sequencing by collision induced dissociation (CID) has become method of choice in mass spectrometry-based proteomics. The development alternative fragmentation techniques such as electron transfer (ETD) extended possibilities within tandem spectrometry. Recent advances instrumentation allow fragment ions to be detected with high speed and sensitivity (e.g., a 2D or 3D ion trap) at resolution accuracy an Orbitrap ToF). Here, we describe comprehensive experimental...
Article25 July 2017Open Access Transparent process Capturing protein communities by structural proteomics in a thermophilic eukaryote Panagiotis L Kastritis orcid.org/0000-0002-1463-8422 European Molecular Biology Laboratory, Structural and Computational Unit, Heidelberg, Germany Search for more papers this author Francis J O'Reilly Chair of Bioanalytics, Institute Biotechnology, Technische Universität Berlin, Thomas Bock orcid.org/0000-0002-9314-5318 Yuanyue Li orcid.org/0000-0001-5971-0355...
Abstract Diminishing potential to replace damaged tissues is a hallmark for ageing of somatic stem cells, but the mechanisms remain elusive. Here, we present proteome-wide atlases age-associated alterations in human haematopoietic and progenitor cells (HPCs) five other cell populations that constitute bone marrow niche. For each, abundance large fraction ~12,000 proteins identified assessed 59 subjects from different ages. As HPCs become older, pathways central carbon metabolism exhibit...
Metal and metal oxide chelating-based phosphopeptide enrichment technologies provide powerful tools for the in-depth profiling of phosphoproteomes. One weakness inherent to current strategies is poor binding phosphopeptides containing multiple basic residues. The problem exacerbated when strong cation exchange (SCX) used pre-fractionation, as under low pH SCX conditions phosphorylated peptides with residues elute bulk tryptic digest therefore require more stringent enrichment. Here, we...
Here, we describe an in-house built ultra-high pressure liquid chromatography (UHPLC) system, with little complexity in design and high separation power combined convenience operation. This system enables the use of long columns 40 cm packed 1.8 μm particles generating pressures below 1000 bar. Furthermore, could be operated at flow rates between 50 200 nL min−1 while maintaining its power. Several gradients were optimized ranging from 23 to 458 minutes. With longest gradient identified over...
Several enrichment and separation strategies are available that allow nearly pure phosphopeptide pools to be created. These too complex completely unraveled by RP-LC-MS analysis alone. Here, we implement weak anion exchange (WAX) chromatography as an additional, complementary dimension strong cation (SCX) reversed phase (RP). Initially, used SCX fractionate a human lysate digest generate fraction highly enriched for phosphopeptides. Analysis of this single with 140 min gradient method...
In order to understand cellular signaling, a clear understanding of kinase-substrate relationships is essential. Some these are defined by consensus recognition motifs present in substrates making them amendable for phosphorylation designated kinases. Here, we explore method that based on two sequential steps strong cation exchange chromatography combined with differential stable isotope labeling, define kinase high accuracy. We demonstrate the value our evaluating very distinct kinases:...
We present a straightforward method to enrich phosphopeptides with multiple basic residues, an under-represented class in common enrichment strategies. Our is based on two-dimensional strong cation exchange (SCX) strategy, operating at two different acidic pHs, enabling both separation and of classes phosphopeptides. The principle the change net charge phosphorylated peptides under conditions second SCX, whereas regular remains unchanged, thus charge. Application our tandem SCX approach...
Abstract Mechanical and metabolic cues independently contribute to the regulation of cell tissue homeostasis. However, how they cross-regulate each other during this process remains largely unknown. Here, we show that cellular metabolism can regulate integrin rigidity-sensing via sphingolipid pathway controlled by amino acid transporter coreceptor CD98hc (SLC3A2). Genetic invalidation in dermal cells impairs rigidity sensing mechanical signaling downstream integrins, including RhoA...
We developed a comprehensive resource for the genome-reduced bacterium Mycoplasma pneumoniae comprising 1748 consistently generated '-omics' data sets, and used it to quantify power of antisense non-coding RNAs (ncRNAs), lysine acetylation, protein phosphorylation in predicting abundance (11%, 24% 8%, respectively). These factors taken together are four times more predictive proteome than mRNA abundance. In bacteria, post-translational modifications (PTMs) ncRNA transcription were both found...
Disruption of epithelial architecture is a fundamental event during tumorigenesis. We show that the expression cancer-promoting phosphatase PRL-3 (PTP4A3), which overexpressed in several cancers, polarized MDCK and Caco2 cells leads to invasion formation multiple ectopic, fully lumens cysts. Both processes disrupt are hallmarks cancer. The pathological relevance these findings supported by knockdown endogenous MCF-7 breast cancer grown three-dimensional branched structures, showing rescue...
<p>Expression proteomic signature</p>
<p>Photo affinity labelling (PAL)</p>
<p>Steroidomics</p>
<p>Transcriptomic signature</p>
<p>Supplementary Materials and Methods</p>
<p>PARP1 PARP2 engagement (ITDR)</p>
<p>panPARP matrix (affinity enrichment chemoproteomics)</p>
<p>Selectivity profile live cells (2D-TPP)</p>
<p>Niraparib matrix (affinity enrichment chemoproteomics)</p>
<p>Co-inhibition of PARP and cholesterol biosynthesis pathway increase efficiency tumor cell killing</p>