HSCT AND JAK-STAT · Role and Modulation of Jak and STAT signaling in Graft Rejection and Graft versus Host Disease
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2011-02-01 → 2014-01-31
- Финансиране от ЕС
- 75 000 €
- Участници
- 1
- Схема
- MC-IRG
Линиите свързват координатора с партньорите.
Накратко на български
Сигналите на протеините Jak и STAT се анализират, за да се разбере как влияят на отхвърлянето на трансплантирани стволови клетки или върху развитието на болестта „транспланта срещу гостоприемник“. Това помага за разработването на нови стратегии за намаляване на смъртността при тези пациенти.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Цел на проекта
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.
Оригинален текст от CORDIS (на английски).
Участници
- FONDAZIONE IRCCS ISTITUTO NAZIONALE DEI TUMORI · MilanКоординаторИталия
Връзки
Данни: CORDIS, © Европейски съюз