Objective
Acute graft-versus-host disease (GVHD) and leukemia relapse cause 75% of the mortality of patients having undergone allogeneic hematopoietic cell transplantation (allo-HCT). A better understanding of signalling in immune cells, tissue specific cell types and leukemia cells is key to develop novel therapies against GVHD and leukemia relapse. The ambitious overall goal of AlloCure is to identify the pathogenic events that initiate GVHD (1), maintain therapy-refractory GVHD (2) and mediate immune escape causing leukemia relapse (3). To address these high risk/high gain questions novel methods and developments across disciplines are required. (1) I hypothesize that a loss of to date unexplored intestinal enteroendocrine cells promotes GVHD initiation. To study these small cell subsets, we will use reporter genes and novel imaging methods to systematically evaluate their fate and signalling during intestinal GVHD. (2) Signalling propagating refractory GVHD is not well-understood. Our phospho-proteomics data set from corticosteroid- and ruxolitinib-refractory GVHD patients will instruct selective analysis of kinase activation in immune cells and enterocytes by using genetic Cre-lox-based and pharmacological approaches. (3) I have shown that leukemia-derived lactic acid inhibits glycolysis and MEK/ERK signalling in T cells, thereby impairing graft-versus-leukemia (GVL) effects. Here, I will decipher which other leukemia-derived metabolites mediate pathogenic signalling in immune cells and test if oncogenic signalling in leukemia cells drives immunosuppressive metabolite production. To enhance GVL we will inhibit pathogenic kinase activation in leukemia cells and myeloid suppressor cells. Using high risk/high gain approaches in a combination of murine and human studies AlloCure aims to develop individualized therapeutic strategies to interfere with pathogenic signalling responsible for GVHD or leukemia relapse to reduce the mortality rate of patients undergoing allo-HCT.
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.
- social sciences sociology demography mortality
- medical and health sciences clinical medicine emergency medicine graft versus host disease
- medical and health sciences clinical medicine transplantation
- medical and health sciences clinical medicine oncology leukemia
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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.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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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.
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-ERC - HORIZON ERC Grants
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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) ERC-2022-ADG
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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.
79106 Freiburg
Germany
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.