Objective
Acute Myeloid Leukemia (AML) is a poorly treatable leukemia in which a limited set of genes are involved. Trib2 is a gene that has not previously been associated with leukemia. My goal is to understand the pathogenesis of Trib2-induced acute myelogenous leukemia (AML). I identified Trib2 as a novel leukomogen that efficiently induces a clonal, transplantable AML in mice. Trib2 inhibits C/EBPalpha to cause AML, and elevated Trib2 expression associates with a cluster of human AML samples that have disrupted C/EBPalpha. This proposal will identify genetic events that cooperate with Trib2 and the Trib2 structural requirements for AML induction. Aim 1 will define the structural and functional domains of Trib2 that contribute to AML, and the domains required for C/EBPalpha inhibition. This will set the stage for Aim 2, which will identify the biochemical mechanism of Trib2-mediated C/EBPalpha degradation, and the mechanism involved in the Trib2-mediated degradation of other potential proteins. Aim 3 will ascertain cooperating events that contribute to Trib2-induced AML. The clonality of the Trib2-induced tumors suggests that the proviral integration site itself may activate genes that cooperate with Trib2. I will identify these proviral integration sites and determine whether genes at these sites synergize with Trib2 in AML pathogenesis. Together, my studies will reveal new pathogenic mechanisms and therapeutic opportunities in this aggressive cancer, which is not currently curable in the majority of patients.
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 biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology leukemia
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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.
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.
FP7-PEOPLE-IRG-2008
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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.
Coordinator
T12 YN60 Cork
Ireland
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