Project description
Spatial proteomics to decode liver fibrosis regression in alcohol-related disease
Liver fibrosis – the accumulation of scar tissue – is a critical stage of alcoholic liver disease. Progression can result in cirrhosis and liver failure. Intervention can lead to regression but not in all patients. With the support of the Marie Skłodowska-Curie Actions programme, the RESOLiVER project aims to reveal the unknown molecular mechanisms and predictors of regression after treatment. It will leverage a rare cohort of biopsies collected before and after treatment from both responders and non-responders. Spatial proteomics data will train machine learning models to predict treatment response and identify clinically applicable protein signatures. Proteomics and phosphoproteomics could also capture dynamic extracellular matrix changes, the hallmark of liver fibrosis.
Objective
Alcoholic liver disease (ALD) is a major global health burden, with liver fibrosis representing a critical stage. Although fibrosis can regress after treatment, the molecular drivers and predictors of patient response remain unknown. RESOLiVER aims to bridge this knowledge gap using powerful and novel approaches and a unique cohort of ALD biopsies collected pre- and post-treatment from both responders and non-responders.
Macrophages and fibroblasts are critical for fibrosis regression. Deciphering their dynamics necessitates sensitive protein measurement with high spatial resolution, enabling precise quantification of molecular changes undetectable by other modalities. The host laboratory of Professor Matthias Mann is ideally suited for this investigation, given their pioneering method development, state-of-the-art instrumentation, and unparalleled proteomics expertise.
Using insights from spatial proteomics, I will develop machine learning models to predict treatment responses and identify protein signatures for clinical application. Additionally, I will employ proteomics and phosphoproteomics approaches to capture dynamic extracellular matrix (ECM) changes - the hallmark of liver fibrosis - and active cross-regulation between ECM and adjacent cells. This is enabled by recent host lab developments in ultra-sensitive phosphoproteomics from low input amounts.
The convergence of clinical expertise and distinctive patient cohorts from collaborators, unmatched proteomics capabilities of the host laboratory, and my profound background in liver research and computational analysis provides RESOLiVER with complementary skillsets to tackle this challenge. By elucidating molecular drivers of fibrosis regression and progression, RESOLiVER will advance fundamental understanding of liver disease and provide actionable insights to guide prognosis, inform therapeutic strategies, and improve ALD management.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences clinical medicine hepatology
- natural sciences computer and information sciences artificial intelligence machine learning
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2025-PF
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80539 MUNCHEN
Germany
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