Project description
Mechanistic insight into PIK3CA-related overgrowth spectrum
PIK3CA-related overgrowth spectrum (PROS) encompasses disorders associated with overgrowth of certain parts of the body as well as vascular lesions. PROS is caused by activating mutations in the PIK3CA gene in somatic cells, and patients undergo extensive surgery, with a high risk of disease recurrence. The EU-funded PROS-VARIANT project aims to understand the molecular mechanisms underlying PROS development. More specifically, researchers will determine the timing, the cell type and the PIK3CA variant that contribute to PROS severity. The molecular evidence will be validated in preclinical models and will fuel future research towards new treatments.
Objective
PIK3CA-related overgrowth spectrum (PROS) is a group of rare congenital disorders that manifest as complex syndromes with overgrowth of several tissues (vasculature, adipose and muscle tissues, bones, brain and skin among others) or as localized lesions such as vascular malformations. PROS is caused by somatic activating mutations in the PIK3CA gene that arise postzigotically during embryonic development. Patients suffer dramatic functional and life-threatening complications and typically require extensive mutilating surgery, pulsed laser, and/or sclerotherapy. However, these treatment strategies are insufficient, and patients commonly experience a high risk of recurrence and progression. This is in part a reflection of poor understanding of the underlying cellular and molecular mechanism of their onset and progression. In this proposal, I aim to gain physiological and molecular insight into PROS and address fundamental biological questions concerning when (timing), where (cell linage), who (PIK3CA variant) and how (triggered mechanism) activating PIK3CA variants contribute to the development and severity of PROS. I will address the following key objectives: 1) identify the specific molecular and cellular alterations triggered by strong (H1047R) and weak (E726K) activating PIK3CA variants and 2) characterize their spatiotemporal pathogenesis in PROS using novel mice models. To this end, a combination of in vitro and in vivo approaches, using novel genetically modified mice will be implemented in order to provide new mechanistic insight into the underlying disease pathology and give rise to new preclinical models to test therapeutic treatments. Achieving these goals will strongly contribute to my training as international expert in PI3K signaling, cell biology and congenital diseases, my experimental skillset, and my development towards a well-embedded and independent researcher within European academia.
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 genetics mutation
- medical and health sciences basic medicine pathology
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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.1.3. - 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 - Marie Skłodowska-Curie Individual Fellowships (IF)
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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-2020
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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.
08916 Badalona
Spain
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.