Objective
The liver is a crucial organ in metabolism and removal of waste products from the body. Hereto, the liver parenchyma receives a mix of nutrient-rich blood from the portal vein and oxygen-rich blood from the hepatic artery. Blood flows through the sinusoids and leaves the liver via the central and hepatic veins. Hepatic sinusoids are highly specialised channels in which hepatocytes are organised in zones according to their position relative to the portal and central veins. They are lined with a specified, fenestrated, discontinuous endothelium. Many drugs (e.g. chemotherapeutics) and toxins cause damage to the sinusoids that may lead to liver fibrosis and cirrhosis. Formation of new sinusoids is an indispensible step for liver regeneration. Furthermore, liver sinusoidal endothelial cells (LSECs) produce agents that stimulate hepatocyte proliferation. Time-dependent expression of different proteins in the developing liver is important for sinusoid formation. The host lab found that the transcription factor Zeb2 (also known as Sip1) is highly expressed in LSECs in the developing and adult liver. Furthermore, its expression in adult LSECs is mainly in those from the pericentral zone. We hypothesize that Zeb2 is a transcriptional determinant of LSEC specification, zonation, maintenance and regeneration. Here, we aim to: (i) evaluate whether/how Zeb2 contributes to LSEC specification and zonation; (ii) establish a role for Zeb2 in LSECs in adult mice; (iii) assess its role in sinusoidal regeneration during liver disease; and (iv) estimate the therapeutic potential of Zeb2-treated endothelial progenitors in recovery from liver injury. To address these aims, we will use a multidisciplinary approach based on lentiviral overexpression in cultured ECs, transgenic mice lacking or overexpressing Zeb2 in ECs and transplantation of ECs pre-specified towards LSECs. These studies will allow us to evaluate the potential of Zeb2 as a novel target to stimulate liver regeneration.
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 basic medicine pharmacology and pharmacy pharmaceutical drugs
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine hepatology
- medical and health sciences health sciences nutrition obesity
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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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF-EF-RI - RI – Reintegration panel
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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) H2020-MSCA-IF-2014
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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.
3000 LEUVEN
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.