M.D., Ph.D., F.R.C.P.(C), F.R.S.C
Dr. Sauvageau’s laboratory focuses on the characterization of the mechanisms by which normal (and leukemia) blood stem cells uniquely undergo self-renewal divisions, a process deemed critical for successful stem cell transplantation and leukemic outgrowth. This notably led to the development of the small molecule UM171 that promotes the expansion of human cord blood-derived stem cells ex vivo.
Guy Sauvageau also oversees the Leucegene initiative which represents one of the most comprehensive efforts to characterize the genetics of acute myeloid leukemia and to develop novel therapeutic strategies.
OUR PROGRAMS
Thes multidisciplinary programs integrate cutting-edge approaches in functional genomics, epigenetics, bioinformatics, (stem) cell biology, biochemistry, pharmacology, medicinal chemistry, and preclinical in vivo mouse studies
Stem Cells and Immune Regeneration Program
One major research focus of the lab is understanding the regulatory networks governing hematopoietic stem cell (HSC) self-renewal and developing innovative strategies to expand these cells for clinical applications. As they age, HSCs gradually lose their lymphoid and regenerative potential, increasing the risk of hematologic cancers and immune dysfunction. Aging also represents a major risk factor for solid cancer, cardiovascular disease, and neurodegenerative disorders.
A major breakthrough from our lab was the discovery of the small molecule UM171, and its target KBTBD4, an E3 ubiquitin ligase involved in epigenetic remodeling. This pioneering work has reshaped our understanding of stem cell self-renewal and rejuvenation, with broad implications for cancer treatment and regenerative medicine.
This research program is structured around two main axes, with strong cross-interactions between them:
1 – Led by Jalila C.: Exploring the molecular and cellular mechanisms that regulates stem cell regenerative processes with a focus on revitalizing the immune system for transplantation and age-related therapies.
2 – Led by Houssam I.: Enhancing the potency, selectivity, and pharmacokinetic profile of the UM171 small molecule series and assess its impact on key aging hallmarks in proof-of-concept animal studies.
Bioinformatics analyses overseen by Jean-François S.
Genomics and Therapeutic Characterization Program of Acute Myeloid Leukemia
Acute myeloid leukemia (AML) remains a highly heterogeneous disease with limited therapeutic options and poor clinical outcomes. While significant efforts have been made to characterize AML at the genomic and transcriptomic levels, rare but recurrent genetic subgroups remain overlooked. This shortcoming obviously limits the development of tailored treatments. To address this gap, the program leverages the Leucegene dataset, which includes 691 primary AML specimens obtained from the Quebec Leukemia Cell Bank. This dataset has been carefully selected to capture the full genetic diversity of AML.
1 – Led by Jean-François S.: By applying advanced bioinformatics methodologies and machine learning approaches on various data types obtained from this cohort (e.g. bulk RNAseq, WGS, WES, single-cell sequencing), the team aims to uncover novel genetic anomalies and identify potential drug vulnerabilities in AML. The ultimate goal is twofold: to deepen our understanding of AML pathophysiology and, with close collaboration from the AML therapeutic program, to uncover relevant insights that can guide the development of more effective treatments.
2 – Led by Céline M.: Leveraging the genetic characterization of a large cohort of primary AML specimens from the Leucegene dataset, our goal is to identify and develop more effective treatments for the aggressive subtypes of AML. By screening extensive compound libraries, we have identified novel molecules with selective anti-AML activities, which we are optimizing in collaboration with chemists of the Drug Discovery Unit at IRIC.
Advancing Metabolic Therapies for Hard-to-Treat Cancers
Led by Houssam I.: Our goal is to develop more effective treatments for aggressive cancers, including lung, pancreatic, and liver cancers, and to advance them to clinical trials. We are focused on two anti-cancer metabolic drugs that synergistically kill cancer cells. Leveraging the medicinal chemistry expertise of Dr. Anne Marinier’s Drug Discovery Unit at IRIC, we are optimizing these drugs to enhance their efficacy. Given the variability in tumor responses, we are assembling a diverse panel of patient-derived tumor samples through clinical collaborations across Canada.