Objective
Our interest is to extend the understanding of Jak and STAT signaling in the immunologic processes conditioning the outcome of allogeneic hematopoietic stem cell transplant (allo-HSCT) and to develop new strategies to overcome graft rejection (GR) and graft versus host disease (GVHD).
Allo-HSCT is a potentially curative strategy for many patients. GR and GVHD hamper the success of allo-HSCT by conditioning treatment related mortality. The Janus family of kinase (Jaks) dictates T helper (Th) cells differentiation through the activation of different members of the STAT family.
We hypothesize that Jak and STAT signaling play an important role for mediating GR and GVHD and propose to: 1) evaluate the activation of Jaks and STATs after transplant in patients with or without GVHD; 2) analyze the kinetics of activation of Jaks and STATs in mouse models of GR and GVHD; 3) determine whether Jak3 has a non-dispensable role in alloreactive-driven, such as GR and GVHD, or homeostatic-driven T cell expansion; 4) explore the possible interaction between STAT6 and STAT1 to dictate Th differentiation; 5) modulate GR and GVHD through the pharmacological manipulation of Jak signaling.
We plan to achieve these objectives by an inter-disciplinary approach consisting of the analysis of in vitro experiments, in vivo data and clinical data. Jak and STAT signaling will be studied on lymphocytes form patients undergoing allo-HSCT. In parallel, in vivo mouse models will explore the role of different Jak-STAT molecules in the onset of GR and GVHD by PCR, phospho-flow cytometry and western blotting. We will utilize mice deficient for different Jak-STAT molecules to demonstrate the causal role of these proteins in GR and GVHD. These mouse models will be instrumental to test the efficacy of new drugs that can modulate Jak and STAT signaling, such as CP-690,550.
Funding of this proposal will foster the European reintegration of a scientist with extensive training in the United States.
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.
- social sciences sociology demography mortality
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine emergency medicine graft versus host disease
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
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-2010-RG
See other projects for this call
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
20133 Milan
Italy
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.