The research work carried out in the Sauvageau lab focuses on the study of hematopoietic stem cells (HSCs) and acute myeloid leukemia (AML). Dr. Sauvageau’s research has led to major breakthroughs in the study of HSCs and AML, notably the identification of several epigenetic regulators in HSC self-renewal, the discovery of the UM171 molecule that promotes the expansion of human cord blood-derived HSCs, as well as the identification of multiple mutations, gene expression profiles and vulnerability to chemical agents for the various AML subgroups.
The laboratory’s research program includes the elucidation of the mechanisms governing HSC specification and self-renewal and the identification of innovative strategies to expand these stem cells in culture for clinical purposes. HSCs are widely used in transplantation to cure many blood diseases, but unfortunately, a compatible donor is unavailable for 40% of patients. Cord blood is a very promising source of stem cells for transplantation, but its use is limited by the low stem cell dose in a cord blood unit. Dr. Sauvageau’s team, in collaboration with Anne Marinier’s group, discovered the UM171 molecule, which promotes the expansion of human cord blood-derived HSCs ex vivo. This breakthrough led to the initiation of a clinical trial aimed at assessing the therapeutic benefits of UM171-expanded cord blood cell transplantation for the treatment of various hematological diseases. The HSC program of the Sauvageau laboratory aims to better characterize HSCs and to identify additional innovative strategies to further improve HSC expansion, optimize cord blood graft composition and translate these discoveries into clinical applications for AML treatment.
Dr. Sauvageau is also the leader of the Leucegene Project, which aims to improve AML stratification and identify new therapeutic solutions for this disease using an integrated approach combining genomics, bioinformatics, medicinal chemistry, molecular and cell biology, as well as proteomics. RNA sequencing and chemical screening of primary AML specimens from the Quebec Leukemia Cell Bank have already led to a better characterization of the various AML subgroups in terms of mutations and gene expression profiles, as well as to the identification of molecules selectively targeting AML subtypes. The Leucegene team, in collaboration with Josée Hébert’s group, has also developed and validated a novel AML prognostic test that predicts resistance to current therapies. The genetic and chemical characterization of AML subgroups continues in order to identify novel therapies for the disease. This research program now also includes the analysis of the surface proteome of the various AML subgroups in order to identify antigens specific to each subtype that could eventually be targeted using immunotherapeutic approaches.