Objective
The Gadd45 family plays a critical role in several cellular functions, including genomic stability, cell cycle regulation and apoptosis. Gadd45a is transcriptionally activated by the tumour suppressor gene p53, which is mutated in more than 50% of human tumours. Studies performed by the applicant have demonstrated that Gadd45a is an important negative regulator of T cell proliferation. Lack of Gadd45a leads to the development of an autoimmune disease remarkably similar to human lupus. Little is known about the molecular mechanism that leads to this autoimmune disease, which affects approximately 0.5% of the world's population. Recently, the applicant demonstrated that T cells derived from Gadd45a-null mice showed constitutive p38 activation, hyper-proliferative response and lower threshold of activation leading to lupus. Gadd45a is a p38 inhibitor in T cells.
Gadd45a prevents phosphorylation of tyr323 in p38, inhibiting its activation. The applicant has obtained a patent ¿Modulating p38 Kinase activity¿ (PCT App lication# PCT/US2005/003379) that describes how inhibition of phosphorylation of tyr323 in p38 is a key therapeutic target in autoimmune diseases such as lupus, rheumatoid arthritis, Crohn's disease, multiple sclerosis and some types of leukemias. The main goals of this project are a) characterization of the Gadd45 family as autoimmune disease suppressor and/or tumour suppressor genes, and b) analysis of the molecular mechanism to obtain a therapeutic target in the treatment autoimmune diseases and/or tumours.
We will generate and characterize deficient murine models in Gadd45a, Gadd45b and Gadd45g and double knockouts Gadd45ab-/-, Gadd45ag-/- and Gadd45bg-/-. We will analyse proliferation, apoptosis, differentiation and production of cytokines in T cells. The results of this project should allow us to discover new key therapeutic targets to fight against autoimmune diseases and/or cancer
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 rheumatology
- natural sciences biological sciences genetics DNA
- medical and health sciences basic medicine neurology multiple sclerosis
- medical and health sciences basic medicine immunology autoimmune diseases
- medical and health sciences clinical medicine oncology leukemia
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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)
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.
FP6-2004-MOBILITY-12
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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.
IIF - Marie Curie actions-Incoming International Fellowships
Coordinator
MADRID
Spain
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