Eirini TROMPOUKI invites Marie-Laure ARCANGELI from Gustave Roussy Institute for an external seminar ,open to the scientific community, on Monday 19 May at noon – Faculty of Medicine – Auditorium 2.

« Role of the stress response protein REDD1 in normal and pathological hematopoiesis« 

Abstract: The REDD1 protein, encoded by ddit4, is a stress protein whose expression is induced by genotoxic stress such as irradiation or chemotherapies. REDD1 is a well-known inhibitor of the mTOR signaling pathway. Recent data have shown that REDD1 can modulate reactive oxygen species (ROS) levels in mTOR-dependent and independent manner. Using mice deficient for ddit4 (Redd1KO) we are studying how REDD1 can participate in HSC maintenance at steady state and upon genotoxic stress. In particular, REDD1 being at the crossroad between stress response and metabolic adaptation, we investigate the function of REDD1 in the metabolic adaptation of HSC to stress.  Moreover,  in silico, using TGCA cohort, it is shown that REDD1 overexpression is bad prognosis factor in acute myeloid leukemia (AML) et is associated with chemoresistance. Therefore we speculate that during leukemic transformation and during leukemic cell response to treatment, REDD1 expression will allow leukemic cells to be protected against chemotherapies, by hijacking REDD1-dependant mechanisms of HSC. Here, we propose to investigate the role of REDD1 in leukemic growth and in leukemic cell responses to chemotherapies in vitro, using human AML cells lines expressing DDIT4/REDD1(OCI-AML3 or MOLM14) and mouse model of leukemogenesis.