Project description
Restoring haematopoiesis in the elderly after chemotherapy
Chemotherapy remains the conventional treatment for many types of cancer. However, it presents with adverse side effects such as myelosuppression and life-threatening neutropenia, especially in elderly patients. Scientists of the EU-funded ReSinAge project are interested to investigate the role of bone marrow sinusoidal endothelial cells on haematopoietic recovery and niche regeneration after chemotherapy. The scientific team proposes to rejuvenate vascular endothelial stem cells by targeting specific transduction pathways. Moreover, they will employ a number of cutting-edge approaches to investigate the impact of such intervention strategies on survival after chemotherapy in the elderly.
Objective
Cancer is a disease of the elderly and chemotherapy remains the mainstay of treatment. The benefits of chemotherapy include increased overall survival, improvement in quality of life, and palliation of symptoms. However, older patients are more susceptible to specific toxicities of chemotherapy, like myelosuppression and life-threatening neutropenia.
Among the tissues strongly affected by chemotherapy, the bone marrow sinusoidal endothelial cells constitute the most important supportive niche for aged hematopoietic stem cells function and for myelopoietic recovery in the elderly. Up to now, few data are available about how aged sinusoidal niches regenerate upon chemotherapy damage and whether it is possible to rejuvenate vascular endothelial stem cells and improve the regeneration of the old sinusoidal niche as an effective strategy to improve HSC function and prevent myelosuppression and life-threatening neutropenia in the elderly.
Here I hypothesize that the reduced regenerative capacity of aged sinusoidal niches can be improved by rejuvenating vascular endothelial stem cells in vivo via targeting Cdc42 activity and the Notch:Jag2 signaling. The current proposal investigates whether improving the regeneration of the aged sinusoidal niche might represent an important target to enhance the hematopoietic recovery and increase the survival after chemotherapy in the elderly.
By combining several ground-breaking approaches ranging from single-cell sequencing, whole-mount bone marrow imaging, deep learning strategies for data analysis and integration, stem cell sorting techniques and specific mouse models, this research project will demonstrate that aging is not irreversible and that targeting the stem cell niche could represent an unprecedented innovative strategy to improve the regenerative capacity not only of hematopoietic stem cells.
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.
- natural sciences biological sciences cell biology cell signaling
- medical and health sciences clinical medicine oncology
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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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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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.
ERC-COG - Consolidator Grant
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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-2020-COG
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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.
08908 L'Hospitalet De Llobregat
Spain
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