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Modulating Tregs in liver disease for therapeutic benefit

Objective

Regulatory T cells (Tregs) are important for maintaining tolerance to self and are known to contribute to appropriate priming in the case of foreign challenges, however, their role in liver homeostasis and disease remains to be determined. Liver disease represents a significant global health issue with Hepatitis B Virus (HBV), Metabolic dysfunction-associated Steatotic Liver Disease (MASLD), and Hepatocellular Carcinoma (HCC) resulting in considerable morbidity and mortality worldwide and limited treatments are available to address these conditions. This project aims to identify novel mechanisms of targeting Tregs in liver disease to suggest methods to manipulate these cells for therapeutic benefit. Cutting-edge mouse models of HBV, MASLD, and HCC will be used to determine the phenotypes, kinetics, and localisation of Tregs in the liver under homeostasis and during disease. High parameter flow cytometry, spatial transcriptomics, and state-of-the-art intravital imaging will allow us to investigate high-resolution spatiotemporal dynamics of liver Tregs to identify novel molecules, interactions, and functions of these cells. Tissue samples from human patient HBV and HCC cohorts are available to the host lab and can be used to screen and refine the molecules of interest identified in mouse liver Tregs to focus further investigation on clinically relevant molecules. The role of Tregs in T cell priming in HBV, and effects on MASLD progression, and HCC development will be determined using mouse models to specifically deplete Tregs, or delete molecules of interest in Tregs, at defined disease stages. Overall, this project will significantly advance our understanding of Tregs in the liver and has the potential to reveal promising clinical targets. The training in experimental techniques, research communication, and transfer of knowledge my career will be developed towards my goal of becoming an independent researcher.

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Keywords

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Programme(s)

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Topic(s)

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.

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.

(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

OSPEDALE SAN RAFFAELE SRL
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.

€ 188 590,08
Address
VIA OLGETTINA 60
20132 Milano
Italy

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Region
Nord-Ovest Lombardia Milano
Activity type
Private for-profit entities (excluding 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.

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