Project description
Forget me not: liver cell interactions in non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease (NAFLD) is associated with excessive accumulation of fat in the liver and may lead to significant pathologies including infections and liver damage. There are no pharmacological treatments for NAFLD, and patients are advised to lose weight. The working hypothesis of the ForgettingNAFLD project funded by the Marie Skłodowska-Curie Actions programme is that the liver possesses memory of inflammation and weight loss is insufficient to restore homeostasis. Researchers aim to investigate the cell interactions in the NAFLD liver and how their perturbation is responsible for this tissue memory. Results may serve as the foundation for resetting cell circuits as a novel treatment in NAFLD patients.
Objective
With the obesity epidemic, global prevalence of non-alcoholic fatty liver disease (NAFLD) is currently at 25% and rising. NAFLD results from accumulation of excessive fat in the liver and covers a spectrum of disease states from simple steatosis (fatty liver) to severe non-alcoholic steatohepatitis (NASH). NAFLD patients are also at increased risk of developing secondary pathologies, including infections and paracetamol-induced liver damage, although the mechanisms behind this remain unclear. As no pharmacological treatment of NAFLD exists to date, patients are typically instructed to lose weight as this can alleviate symptoms. However, with the recent proposal of tissue memory of inflammation, including NAFLD, it is unclear if weight loss alone is sufficient to restore liver homeostasis or if recovered NAFLD patients remain more susceptible to secondary inflammatory events. Recently, the host labs have identified key cell-cell circuits that control the functional specialization of liver resident macrophages in the steady-state and fatty liver. These findings led me to hypothesize that NAFLD could lead to tissue memory by disrupting the interactions between resident liver cells and establish aberrant cell-cell circuits that maintain a pathological state even after weight loss. Furthermore, I postulate that this NAFLD memory could facilitate the relapse into NAFLD but also modulate susceptibility to secondary insults. Indeed, my preliminary data indicates altered susceptibility to paracetamol overdose. Here, I propose to use single-cell RNA sequencing and epigenetics to investigate how cell-circuits in the liver are perturbed after NAFLD regression and identify the signals underlying these alterations. This project will further our understanding on how liver circuits are distorted in disease and could provide therapeutic avenues to ‘reset’ pathogenic liver circuits in patients currently suffering from NAFLD or those in the process of weight loss and recovery.
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.
- medical and health sciences basic medicine pathology
- natural sciences biological sciences genetics RNA
- medical and health sciences basic medicine physiology homeostasis
- medical and health sciences health sciences nutrition obesity
- natural sciences biological sciences genetics epigenetics
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Keywords
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)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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)
MAIN PROGRAMME
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Topic(s)
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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.
Funding Scheme
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.
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
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2021-PF-01
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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.
9052 ZWIJNAARDE - GENT
Belgium
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.