Hématopoïèse normale et pathologique : émergence, environnement et recherche translationnelle
Director : Stephane GIRAUDIER MD, PhD /stephane.giraudier@aphp.fr
Gestionnaire : Jacqueline Anais /jacqueline.anais@inserm.fr
The UMRS 1131 laboratory is composed of two distinct teams: team 1 is mainly focusing on transfer research on normal and pathological hematopoiesis while the team 2 is conducting a more fundamental research mainly on p53. Both teams collaborate on p53-dependent modifications of hematopoiesis.
Pathological as well as normal hematopoietic cells are in part dictated by hematopoietic cell-extrinsic mechanisms involving clone/environment interactions. Our hypothesis is that mechanisms independent of the cell-intrinsic ‘fitness’ impact the clonal evolution.
This hypothesis has two important consequences, namely that biomarkers of response/relapse/evolution/ transformation of myeloid diseases can only be sought for at the systems’ scale rather than at the clonal scale, and that strategies to channel leukemia adaptability will enhance the efficacy of current and novel treatment strategies to eradicate these pathologies. Following this aim, team 1 focuses on three points: (1) Description of pathological and normal hematopoietic cell emergence and organization of hierarchy and sensitivity to external environment modifications, (2) Description of emergence and hierarchy in normal and pathological myeloid pathologies: Pathologies emerging during childhood (JMML being a paradigm of this) and pathologies emerging during the second part of life (classical MPN) and (3) direct impact of environment modifications (genetic or epigenetic modifications) on myeloid cells behaviour (clone/stroma interactions, clone/cytokine secretion, modifications (epigenetic, transcriptomic, proteomic and functional) of environment during treatments and dynamic structure of tissue growth (homeostatic versus stress hematopoiesis).
The second team’s main research areas have been on the translation control of the p53 message in response to different stresses and signaling pathways and on the Epstein-Barr virus encoded EBNA1. This team also started a project on a non-canonical translation event that precedes the canonical translation of full length proteins and that produces antigenic peptide substrates for the MHC class I pathway.
Team 1 is directed by Stéphane Giraudier and gathers 5 groups dedicated to a translational research in myeloproliferative disorders (MPNs and JMML) with specific skills in foetal hematopoiesis, epigenetics and animal models.
- Group 1: Stephane Giraudier (MD, PhD), Jean-Jacques Kiladjian (MD, PhD), Bruno Cassinat (PharmD, PhD), Nabih Maslah (PharmD, PhD)
- Group 2: Fabien Guidez (CRCN, PhD), and Patricia Krief (CRHC, PhD).
- Group 3 : Rose Ann Padua (Emeritus Director of Research, Ph.D)
- Group 4 : Michèle Souyri (DR Inserm)
- Group 5: Hélène Cavé (PUPH), Aurélie Caye (PH), Elodie Lainey (MCU-PH), Marion Strullu (MCU-PH)
