Objective
The aim of this proposal is to examine the role of inflammatory signalling pathways in murine models of liver and biliary disease by application of conditional gene targeting using cre/loxP technology. Previous studies have provided evidence that the NF-kB pathway and its activating kinase complex – consisting of three subunits: IKK1, IKK2 and NEMO – are crucial regulators of liver physiology and pathology, but their differential, cell specific functions in the liver are currently only poorly understood. The first part of this proposal will focus on the evaluation of molecular mechanisms underlying the development of hepatocellular carcinoma in a setting of chronic hepatitis. By using a novel mouse model of spontaneous liver cancer based on conditional deletion of NEMO in hepatocytes, the functions of cytokines, specific intracellular signalling pathways, the innate and adaptive immune system and the role of hepatic stem cells in hepatitis and carcinogenesis will be examined. In the second part of this proposal, we will extend these studies by evaluating the function of NEMO/NF-kB in other hepatic cell compartments, specifically the function of NEMO in hepatic stellate cells and liver fibrosis, the endothelial function of NEMO/NF-kB in an in vivo model of hepatic ischemia-reperfusion injury and the role of the NF-kB pathway in biliary epithelial cells and inflammatory biliary diseases. Finally, in the third part of this proposal we will analyse the unknown intrahepatic role of non-canonical, IKK1-dependent signalling pathways and the function of TAK1 – a molecule at the interface between inflammatory and developmental pathways – in liver injury, fatty-liver-disease and insulin-resistance. Knowledge gained by these studies and the further understanding of the cell specific hepatic function of NF-kB and related pathways might build the basis for the development of novel pharmacological approaches for the future treatment of liver diseases and cancer in humans.
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 clinical medicine oncology liver cancer
- medical and health sciences health sciences infectious diseases
- medical and health sciences basic medicine immunology
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine hepatology
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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.
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.
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.
ERC-2007-StG
See other projects for this call
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.
Host institution
52074 Aachen
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.