Created in 2008, the Innovative therapies in myeloid leukemias and hematopoietic stem cells team deciphers the molecular and cellular mechanisms involved in the physiological and pathological differentiation of hematopoietic stem cells with a primary focus on cells of the myeloid lineage. We wish to propose new therapeutic opportunities for incurable myeloid hemopathies such as MDS, AML and CMML. Recent advances in the genetic diversity of MDS, AML and CMML have led to the development of more effective therapies, but their integration into a standardized clinical approach is still under debate. In order to contribute to the development and validation of innovative therapies for these hematological diseases, we need to better understand the molecular mechanisms involved in the transformation of myeloid cells. In this context, our team studies the regulation of apoptosis, autophagy, ferroptosis, oxidative stress, differentiation and reprogramming of myeloid cells. Our projects include both fundamental and applied research, with the objective of transferring our discoveries from the laboratory to the clinic through the development of innovative therapies for the benefit of patients.
Projects
G. RobertResearcher
Mail guillaume.robert@univ-cotedazur.fr
P. AubergerResearch Director
Mail patrick.auberger@univ-cotedazur.fr
The lysosome is a key organelle for the uptake and degradation of proteins through a spectrum of processes such as Macroautophagy and Chaperone-mediated Autophagy (CMA). In our research we have highlighted the importance of this organelle during aging and its importance in the genesis of myeloid leukemias. We are currently studying the impact of the invalidation of a lysosomal protein on the deregulation of the hematopoietic compartment and the genesis of myeloid leukemias, using original mouse models.
In collaboration with the Nice Institute of Chemistry, we are developing chimeric molecules called "biodegraders" capable of targeting oncogenic proteins involved in leukemia and dealing with them within the lysosome.
C. FavreauResearch engineer
Mail cecile.favreau@univ-cotedazur.fr
C. SavyResearch engineer
Mail coline.savy@univ-cotedazur.fr
J. BiancoResearch engineer
Mail julie.bianco@univ-cotedazur.fr
M. BourgoinResearch engineer
Mail maxence.bourgoin@univ-cotedazur.fr
A. JacquelResearcher
Mail arnaud.jacquel@univ-cotedazur.fr
P. AubergerResearch Director
Mail patrick.auberger@univ-cotedazur.fr
Cellular Reprogramming
My group focus on the study of myeloid immunosuppressive cells, such as anti-inflammatory macrophages (Leukemia-Associated Macrophages and TAMs) and MDSCs (Myeloid-derived suppressor cells), in hematopoietic malignancies (AML, MDS and CMML). The main function of these cells in cancer is to inhibit the antitumor immune response. Therefore, understanding the molecular mechanisms involved in the generation of LAMs and MDSCs might provide an opportunity for the design of novel therapeutic strategies. A better characterization of their origin, phenotype and ability to trigger an antitumor response and how these different myeloid immunosuppressive subpopulations could be impacted by anticancer therapies is urgently needed to selectively target/reprogram them in different types of leukemia.
P. ChaintreuilPost-doctoral fellow
Mail paul.chaintreuil@univ-cotedazur.fr
E. KerreneurPhD student
Mail emeline.kerreneur@univ-cotedazur.fr
M. BourgoinResearch engineer
Mail maxence.bourgoin@univ-cotedazur.fr
Ml. ArcangeliResearcher
Mail marie-laure.arcangeli@univ-cotedazur.fr
P. AubergerResearch Director
Mail patrick.auberger@univ-cotedazur.fr
This project focuses on HSCs and how their fundamental properties are regulated. Hematopoietic stem cells are capable of producing all blood cells and represent a therapeutic tool of choice for gene/cell therapy, regenerative medicine and transplantation. In addition to their multipotency, they possess an almost infinite self-renewal potential that allows them to keep their numbers stable over time. The self-renewal capacity of HSCs must be finely regulated to avoid the depletion of their reserves by differentiation inducing a defect in the production of blood cells in the periphery and to prevent their leukemic transformation.
It has been shown that hematopoietic progenitors that have undergone leukemic transformation, in particular in the case of acute leukemias, have reacquired the self-renewal and quiescence programs of HSCs, allowing them on the one hand to maintain a pool of leukemic cells capable of initiating and sustaining leukemia, and on the other hand to protect themselves from chemotherapy or radiotherapy treatments. We find, among others, epigenetic actors (DNMT3, TET2) and reactive oxygen species (ROS) playing a role in both HSC self-renewal and leukemic transformation.
The overall goal of the project is to understand how antioxidants can play a role in the regulation of the quiescence and self-renewal capacities of hematopoietic and leukemic stem cells and it is organized around 3 core programs:
I- the role of antioxidants in the regulation of HSC self-renewal capacity ex vivo
II- the role of the stress response protein REDD1 in the response of HSCs after genotoxic stress
III- the role of the REDD1 stress response protein in the leukemic transformation of hematopoietic stem and progenitor cells and in the resistance of leukemic cells to treatments.
C. SavyResearch engineer
Mail coline.savy@univ-cotedazur.fr
M. BourgoinResearch engineer
Mail maxence.bourgoin@univ-cotedazur.fr
Publications
The generation, activation, and polarization of monocyte-derived macrophages in human malignancies.Authors Chaintreuil P, Kerreneur E, Bourgoin M, Savy C, Favreau C, Robert G, Jacquel A, Auberger P
Frontiers in immunology May 2023
Caspase Inhibition Modulates Monocyte-Derived Macrophage Polarization in Damaged Tissues.Authors Solier S, Mondini M, Meziani L, Jacquel A, Lacout C, Berghe TV, Julé Y, Martinou JC, Pierron G, Rivière J, Deloger M, Dupuy C, Slama-Schwok A, Droin N, Vandenabeele P, Auberger P, Deutsch E, El-Benna J, Dang PM, Solary E
International journal of molecular sciences Feb 2023
From normal hematopoiesis to malignancies: Highlights from the 2021 Meeting of the Club Hematopoiesis and Oncogenesis.Authors Troadec MB, Porteu F, Arcangeli ML, Foudi A, Bluteau D, De Sepulveda P, Guillouf C, Mazure NM, Meggetto F, Brunet De La Grange P, Broccardo C
Bulletin du cancer Feb 2023
Show all publicationsPatents
Co-inventors O. Dufies, P. Chaintreuil, J. Courjon, A. Jacquel, P. Auberger, L. Boyer
Co-inventors L. Boyer, P. Auberger, J. Courjon, C. Pomares, V. Giordanengo, O. Visvikis, C. Loubatier, O. Dufies, C. Torre, A. Doye, P. Munro, R. Lotte, A. Jacquel, A. Robert, Stoyan Ivanov; Sebastien Vitale;
Co-inventors A. Jacquel, P. Auberger, Nathalie Droin; Eric Solary