Objective
"Epithelial ovarian cancer is a disease with grim prognosis and high-grade serous carcinoma (HGSC) is its most common subtype. Recent literature suggests that HGSC arises in the fallopian tube (FT) epithelium, rather then in the ovary, and metastasizes to the ovary early on in the process of transformation. This hypothesis is based, among other findings, on common morphologic and immunophenotypic traits between HGSC and the fallopian tube secretory epithelial cell (FTSEC). One of the shared markers between HGSC and FTSEC is the transcription factor PAX8. PAX8 is known to play a critical role in FT organogenesis and as we have shown it is highly conserved in HGSC. I propose to study the role of PAX8 in FTSEC and in HGSC, thereby establishing its role as an essential lineage marker.
In Aim 1 I will investigate whether PAX8 is a critical factor in cells of the FTSEC lineage. For this purpose we will use PAX8 knock down in HGSC cell lines and immortalized FTSEC lines to reveal PAX8’s activity in benign and malignant cells. As part of this aim (Aim 1b) we will test whether BCL2 is a target gene of PAX8 and a direct mediator of PAX8’s anti apoptotic role in FTSEC and HGSC. I will then use expression profiling to suggest and validate additional mediators of PAX8’s activity, thereby defining additional serous determinants.
In Aim 2 I will reveal the genomic binding locations of PAX8 in benign, non-invasive and invasive carcinomas. Towards this aim we will use our unique genetically engineered mouse model of HGSC arising from the FTSEC. We will study PAX8 as a model to ask whether a transcription factor lineage marker, which is conserved throughout transformation, preserves its DNA binding profile, its target genes and its transcriptional regulatory network.
Taken together, the results generated in this study will allow better understanding of the role of PAX8 in FT transformation, and will clarify the role of a transcription factor lineage marker during transformation."
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences genetics DNA
- medical and health sciences clinical medicine oncology
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2013-CIG
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Funding Scheme
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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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
31096 Haifa
Israel
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