HSCT AND JAK-STAT

Role and Modulation of Jak and STAT signaling in Graft Rejection and Graft versus Host Disease

Coordinatore	FONDAZIONE IRCCS ISTITUTO NAZIONALE DEI TUMORI    more  Organization address address: Via Venezian 1 city: Milan postcode: 20133 contact info Titolo: Dr. Nome: Antonio Cognome: Cannarozzo Email: send email Telefono: 390224000000 Fax: 390224000000
Nazionalità Coordinatore	Italy [IT]
Totale costo	75˙000 €
EC contributo	75˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2010-RG
Funding Scheme	MC-IRG
Anno di inizio	2011
Periodo (anno-mese-giorno)	2011-02-01   -   2014-01-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	FONDAZIONE IRCCS ISTITUTO NAZIONALE DEI TUMORI  Organization address address: Via Venezian 1 city: Milan postcode: 20133 contact info Titolo: Dr. Nome: Antonio Cognome: Cannarozzo Email: send email Telefono: 390224000000 Fax: 390224000000	IT (Milan)	coordinator	75˙000.00

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (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.'