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Melanoma cell cell samples (DIA)

ABSTRACT: Whole proteome measurement to determine selectivity profile for compound NK266 in melanoma as well as determining downstream signalling effects of DUB inhibition and degradation.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Farnusch Kaschani

LAB HEAD: Farnusch Kaschani

PROVIDER: PXD063920 | Pride | 2026-04-21

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	ACE_0883_NK45.raw	Raw
	ACE_0883_NK46.raw	Raw
	ACE_0883_NK47.raw	Raw
	ACE_0883_NK48.raw	Raw
	ACE_0883_NK49.raw	Raw

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1 - 5 of 48

Publications

Targeted degradation of USP7 in solid cancer cells reveals distinct effects of deubiquitinase degraders and inhibitors.

Klink Nikolas N Urban Sebastian S Seier Johanna A JA Adhikari Bikash B Schwalm Martin P MP Müller Juliane J Dorsch Madeleine M Steinbach Philine P Jung Jennifer J Vogt Markus M Kaschani Farnusch F Koch Johannes J Führer Siska S Kaiser Markus M Schulze Nina N Knapp Stefan S Wolf Elmar E Paschen Annette A Grüner Barbara M BM Gersch Malte M

Nature communications 20260513 1

Proteolysis-targeting chimeras (PROTACs) co-op the ubiquitin system for targeted protein degradation, creating opportunities to interrogate cellular functions of proteins through "chemical knockdown". However, matched pairs of protein degraders and inhibitors, that possess high specificity and chemical complementarity, for individual components of the ubiquitin system have remained scarce. This includes reagents to modulate activity and abundance of deubiquitinases (DUBs). Here, using an integra ...[more]

PMID: 42129197

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Whole proteome measurement to determine effects of USP7 targeting small molecules in pancreatic cancer cells (Panc89) and melanoma cells (MaMel47)

Project description:Whole Proteome measurement of pancreatic cancer cells (Panc89) or melanoma cells (MaMel47) treated with USP7 inhibitors and degrader to compare phenotypes induced by inhibition compared to degradation. We synthesized and characterized potent USP7-targeting degrader molecules (PROTACs) and compared USP7 degradation to inhibition

2026-04-21 | PXD070431 | Pride

Pancreatic cancer cell samples (DIA)

Project description:Whole proteome measurement to determine selectivitiy profile for compound NK250 in pancreatic cancer as well as determining downstream signaling effects of DUB inhibition and degradation

2026-04-21 | PXD063917 | Pride

Pancreatic cancer cell samples (DDA)

2026-04-21 | PXD063913 | Pride

Competitive target ID for inhibitor NK192

Project description:Competitive target ID for inhibitor NK192. To this end the inhibitor was decorated with biotin and used in a pull-down experiment to pull out the desired on-target (USP7) and possible off-targets. The samples were analysed by LC-MS.

2026-04-21 | PXD063889 | Pride

Altered Brain Energy Metabolism in the APPPS1 Alzheimer’s Mouse Model during Anesthesia

Project description:Background: Synaptic transmission and network activity rely on high ATP turnover. Impairments in cerebral energy metabolism are increasingly recognized as central to aging and the pathogenesis of Alzheimer’s disease (AD). AD is related to elevated risk for perioperative neurological complications, including postoperative delirium and further cognitive deterioration. However, the interaction between metabolic vulnerability and anesthetic exposure remains incompletely understood. Methods: We investigated cortical metabolic responses and potassium homeostasis in acute brain slices from wild-type (WT) and AD-like APPPS1 transgenic mice, which were either exposed to isoflurane or left untreated. Glia cells were assessed by staining microglia and astrocytes. Measurements of the cerebral metabolic rate of oxygen (CMRO2), extracellular potassium ([K+]o) dynamics, and proteomic profiling were integrated with computational modeling to assess oxidative metabolism and anesthetic effects under different conditions. Results: APPPS1 mice exhibited reduced CMRO2 and attenuated neuronal activity compared to age-matched WT animals, showing sex-specific differences. Proteomic analysis revealed the downregulation of key mitochondrial and glycolytic enzymes, indicating an impaired capacity for ATP generation. Exposure to isoflurane further suppressed CMRO2, with a more pronounced effect in the APPPS1 brain tissue, while glia cells exhibited no acute changes. Additionally, isoflurane exacerbated deficits in [K+]o clearance, highlighting impaired ion homeostasis under anesthesia. Conclusions: Our findings demonstrate that AD-like pathology is associated with a significant decline in oxidative metabolism and ATP availability. These deficits are exacerbated by anesthetic exposure, contributing to impaired potassium regulation. This suggests that diminished metabolic flexibility may underlie increased anesthetic vulnerability and postoperative complications in AD.

2026-06-08 | PXD072113 | Pride

Characterization of the adsorbed protein layer on orthopedic biomaterials and regenerative effects after the first patient contact

Project description:In this study, we investigate the intraoperative protein adsorption on the synthetic bone substitutes β-TCP (tricalcium phosphate) and PCL (polycaprolactone) using two different adsorption techniques.

2025-10-06 | PXD066010 | Pride

High-throughput proteomics of nanogram-scale samples with Zeno SWATH DIA

Project description:The ability to conduct high-quality proteomic experiments in high throughput has opened new avenues in clinical research, drug discovery, and systems biology. Next to an increase in quantitative precision, recent developments in high-throughput proteomics have also gained proteomic depth, to the extent that earlier gaps between classic and high-throughput experiments have significantly narrowed. Here we introduce and benchmark Zeno SWATH, a data-independent acquisition technique that employs a linear ion trap pulsing (Zeno trap pulsing) in order to increase proteomic depth and dynamic range in proteomic experiments. Combined with the high acquisition speed, these gains in sensitivity are particularly attractive for conducting high-throughput proteomics experiments with high chromatographic flow rates and fast gradients. We demonstrate that when combined with either micro-flow- or analytical-flow-rate chromatography, Zeno SWATH increases protein identification in complex samples 5- to 10-fold when compared to current SWATH acquisition methods on the same instrument. Using 20-min micro-flow chromatography, Zeno SWATH identified > 6,000 proteins from a 62.5 ng load of human cell lysate with more than 5,000 proteins consistently quantified in triplicate injections with a median CV of 6%. Using 5-min analytical-flow-rate chromatography (800 µl/min), Zeno SWATH identified 4,907 proteins from a triplicate injection of 2 µg of a human cell lysate; or more than 3,000 proteins from 250 ng tryptic digest. Zeno SWATH hence facilitates precise proteomic experiments with small sample amounts using a fast and robust high flow-rate chromatographic method, broadening the application space that requires precise proteomic experiments on a large scale.

2022-12-01 | PXD036786 | Pride

Identification of Plasma Biomarkers from Rheumatoid Arthritis Patients Using an Optimized SWATH Proteomics Workflow

Project description:Rheumatoid arthritis (RA) is a systemic autoimmune and inflammatory disease. Plasma biomarkers are critical for understanding disease mechanisms, treatment effects, and diagnosis. Mass spectrometry-based proteomics is a powerful tool for unbiased biomarker discovery. However, plasma proteomics is significantly hampered by signal interference from high-abundance proteins, low overall protein coverage, and high levels of missing data from data-dependent acquisition (DDA). To achieve quantitative proteomic analysis for plasma samples with a balance of throughput, performance, and cost, we developed a workflow incorporating plate-based high abundance protein depletion and sample preparation, comprehensive peptide spectral library building, and data-independent acquisition (DIA) SWATH mass spectrometry-based methodology. In this study, we analyzed plasma samples from both RA patients and healthy donors. The results showed that the new workflow performance exceeded that of the current state-of-the-art depletion-based plasma proteomic platforms in terms of both data quality and proteome coverage. Proteins from biological processes related to the activation of systemic inflammation, suppression of platelet function, and loss of muscle mass were enriched and differentially expressed in RA. Some plasma proteins, particularly acute phase reactant proteins, showed great power to distinguish between RA patients and healthy donors. Moreover, protein isoforms in the plasma were also analyzed, providing even deeper proteome coverage. This workflow can serve as a basis for further application in discovering plasma biomarkers of other diseases.

2023-10-25 | PXD045171 | Pride

Sequence context specific DNA de-methylation shapes progression of IDH mutant oligodendrogliomas and astrocytomas

Project description:Background: Aggressiveness guides treatment in IDH-mutant gliomas. Objective grading of oligodendrogliomas is therefore urgently needed. Material and Methods: 211 primary and recurrent resections from 111 oligodendroglioma patients were collected, complemented with 91 samples for validation. Samples were subjected to Ki-67 staining, proteomics and DNA-methylation profiling. Data were analyzed using various multivariate differential models and algorithms. Results & conclusion: We developed CGCψ, a continuous grading coefficient independent of tumor typing, and demonstrate its prognostic value in oligodendrogliomas. Its prognostic value outperformed WHO grade at tumor recurrence. CGCψ is linked to large scale DNA de-methylation, but increased DNA methylation of polycomb transcription factors, aging, Ki-67, and losses on chr4 and chr9p. DNA de-methylation at tumor recurrence/higher grade is sequence context specific and associated with TET recognition sites. Both oligodendrogliomas and astrocytomas progress along this shared epi-genetic axis. Oligosarcomas are characterized by a high CGCψ and low tumor purity.

2026-01-19 | PXD070222 | Pride

Dietary macronutrient composition on the total proteome of brown adipose tissue in fathers and their offspring

Project description:Brown adipose tissue (BAT) is involved in dissipating energy as heat (non-shivering thermogenesis), not only under cold exposure but also in the dissipation of excess ingested energy. Therefore, harnessing energy utilisation by BAT is a potential avenue to combat weight gain and its comorbidities. Dietary macronutrient composition can directly influence BAT size and has recently been shown to influence BAT size of daughters through non-genetic effects in the patriline of C57BL/6J mice. However, the effects of dietary macronutrient composition and any non-genetic paternal effects on BAT function have yet to be characterised. Using the Geometric Framework for Nutrition, we investigated the effects of dietary protein, carbohydrate, and fat composition on the BAT proteome in male mice (F0) and intergenerational effects in their offspring (F1). In F0 males, >50% of the proteome was affected by dietary macronutrient composition, with distinct clusters of proteins that responded to diet in similar ways. We identified two clusters with inverse expression patterns that correlated with BAT weight. Notably, Ucp1 was reduced on low fat diet compositions that promoted increased BAT mass, while on those same diets there were increased levels of proteins involved in protein turnover. These diets also led to a reduction in proteins involved in purine biosynthesis (often Ucp1 inhibitors) and increased Hsl, which facilitates free fatty acid release, critical for Ucp1 activation. We did not find any effects of paternal diet on the BAT proteome in sons, but paternal protein intake negatively affected Basigin expression in daughters; a protein that regulates Ucp1 transcription. Our study is the first characterisation of BAT protein abundance across a broad range of dietary macronutrient compositions and across two generations, with implications for our understanding of non-shivering thermogenesis and metabolism.

2025-06-27 | PXD060130 | Pride

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