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Oncolipidomics: Why is lipidomic dysregulation pattern in blood similar for various cancers?

Project description

Advancing lipid analysis in cancer

The analysis of lipid profiles in the body helps understand various aspects of human health, offering insights into metabolic disorders and cardiovascular diseases. Accumulating evidence also indicates that cancer is associated with lipid dysregulation, but the reasons behind these observations are not fully understood. Funded by the European Research Council, the ONCOLIPID project aims to unravel the mechanism underlying lipidomic dysregulation in cancer. The working hypothesis is that the lower activity of ceramide synthase is to blame. Researchers will correlate lipidomics data with proteomics and transcriptomics in different types of cancer and also develop specialised analytical software. Project deliverables have the potential to improve lipidome quantitation for diagnostic purposes.

Objective

Lipids are involved in numerous pathways of human metabolism that are related to pathological states. Alterations of lipid concentrations in the blood of cancer patients have been reported but the biological origin is still unknown. Deciphering the mechanisms of the lipid dysregulation mechanism could dramatically change oncology because it can open new avenues for cancer detection with subsequent effective treatment and drug development targeting dysregulated pathways. Early cancer diagnosis is one of the main unmet needs in medicine, which can improve the unfavorable prognosis of patients. The potential of lipidomics has not been fully explored yet, because analytical workflows have limitations in terms of accurate molar quantitation and insufficient coverage of the lipidome. Biologists predict up to 100,000 lipid species in nature, but current methods typically report less than 1% of this number. Here, we will develop novel approaches for quantitation of more than 2,000 lipids from >80 classes using 13C stable isotope labeled internal standards and ultrahigh-resolution methods in liquid or supercritical fluid chromatography, mass spectrometry, and ion mobility. The comprehensive characterization of lipidome will allow us to construct Cancer Lipidome Atlas (WP1). We will develop new Bayesian software for automated data processing and statistical evaluation applicable to the main lipidomic and metabolomic workflows (WP2). We will correlate lipidomics data with metabolomics, proteomics, and transcriptomics data to unravel why lipidomic dysregulation in blood has a similar pattern for various cancers (WP3). This strategy will be applied for the comparison of ten types of cancer with control samples in cell lines, animal models (mice and pigs), human samples (tissues and plasma), and extracellular vesicles. Our initial hypothesis is that the lower activity of CERS2 triggered by cancer cells can downregulate very long fatty acyl ceramides and other sphingolipids.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2022-ADG

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Host institution

UNIVERZITA PARDUBICE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 3 499 413,00
Address
Studentska 95
532 10 PARDUBICE
Czechia

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Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 3 499 413,00

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