Guy Sauvageau

Key Research Areas
Associated Researchers
Associated Organizations

Recent Research Projects

Chemical and Genetic Interrogation of Human HSC Self-Renewal: Towards Optimal Cord Blood Grafts

2015/16-2018/19 • $2,667,324 • PI,Other
HSC/progenitor cell (HSPC) transplantation can cure many hematological diseases when patients have a HLA-matched donor. For mismatched patients, the use of cord blood (CB) is ideal thanks to its immature immune system. As most CB grafts suffer from low cell numbers insufficient for adults,...

A functional surfaceome map of human hematopoietic stem and progenitor cells

2017/18-2018/19 • $417,690 • PI,CO
Hematopoietic stem cells (HSCs) ensure the lifelong production of all essential blood cells in the organism, and transplantation of these cells is used for the treatment of certain types of cancer of the blood system. HSC transplantation (HSCT) requires a stem cell source, typically peripheral...

Assessing the therapeutic potential of E4F1, a new protein of the DNA damage response, in cancer treatment.

2016/17-2018/19 • $105,000 • Scholarship/Fellowship,Other
The lifetime conservation of tissue integrity relies upon a delicate balance between cell division and differentiation. This requires a reliable system to protect the genetic information against harmful DNA damages. Thus, to prevent genetic instability and ensure cell integrity, cells have...

Aberrant expression of the platelet aggregating cell surface protein podoplanin by acute promyelocytic leukemia blasts may explain the bleeding complications associated with this disease.

2017/18-2018/19 • $100,000 • Scholarship/Fellowship,Other
Acute promyelocytic leukemia or APL represents 10% of newly diagnosed patients with acute myeloid leukemia. A portion of patients still die from the important bleedings that uniquely characterize this subgroup, and bleeding complications are more frequent and severe when diagnosis is delayed....

Innovative characterization of structural variants and differential splicing from RNA-sequencing data of 452 primary human AML specimens.

2018/19 • $8,333 • Scholarship/Fellowship,Other
Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and among the leading causes of cancer related deaths in the youngests of them. Despite advances in supportive care to treat therapy-related complications, the majority of AML patients will not exceed the two-year...

Molecular Genetics of Normal and Cancer Stem Cells

2010/11-2017/18 • $1,400,000 • PI
Inability to induce hematopoietic stem cells self-renewal ex vivo remains a major clinical challenge that excludes thousands of patients each year from transplant therapy. Methods that would permit the expansion of these cells ex vivo would be highly beneficial for these patients, including...

Clinical application of a novel molecule that expands human cord blood stem cells

2015/16-2017/18 • $1,013,167 • PI,CO
Allogeneic hematopoietic stem cell transplantation is a life-saving procedure in patients with blood cancers, but only 25% of transplant candidates have a sibling donor. A matched unrelated donor can be found for 60% of patients but this number is lower for non-Caucasians. Cord blood, another...

Stem Cell Network/Réseau de cellules souches

2012/13-2015/16 • $2,061,000 • PI,CO
No summary

BMI1 as a mutlifunctional protein master regulator of stem cell activity

2011/12-2015/16 • $595,634 • PI
Stem cell are characterized by their ability to self-renew, a process which implies the coordination between cell division and cell differentiation. Understanding the basis which underly self-renewal has relevance in regenerative medicine (e.g., stem cell expansion for bone marrow...

Identification of novel pathways essential for blood cell formation

2011/12-2015/16 • $508,098 • PI
Stem cells have received considerable public attention in part because of their potential application in regenerative therapies. Stem cells can be operationally defined as cells that have the unique property to self-renew as well as to generate more differentiated progeny (differentiation)....

Identifying therapeutic targets of the Hox-Meis network that regulate leukemia stem cell fate.

2013/14-2015/16 • $88,556 • Scholarship/Fellowship,Other
Acute myeloid leukemia (AML) is diagnosed annually in ~1,200 patients in Canada. Treatment for this disease has not changed significantly over the last 30 years and the overall survival of AML patients remains close to 20%. Unfortunately, most AML patients relapse within 3 years of diagnosis and...

Functional genomics to identify stem cell fate determinants

2010/11-2014/15 • $1,076,250 • PI
Stem cells have received considerable public attention in part because of their potential application in regenerative therapies. Stem cells can be operationally defined as cells that have the unique property to self-renew as well as to generate more differentiated progeny (differentiation)....

Characterization of the leukemia-inducing NUP98-HOXA9 oncogene using Drosophila and mouse models

2010/11-2013/14 • $577,436 • PI,CO
Oncogenes have the capacity to transform cells and promote cancer. They often result from specific mutations that hyper-activate or change normal gene function and thereby force a cell to engage in a path that it normally does not follow. While a large number of oncogenes have been identified to...

The Polycomb Repressive Complex 2 (PRC2): a mechanistic investigation of its role in normal and leukemia stem cells.

2012/13-2013/14 • $140,000 • Scholarship/Fellowship,Other
The polycomb repressive complex 2 (PRC2) consists of a number of proteins that together regulate the activity of adult stem cells in our body. In the blood system, their tightly regulated activity is important to ensure the life-long production of blood cells. At the same time, it has become...

A novel putative Bmi1-E4F1-Map1s complex regulates self-renewal of hematopoietic stem/progenitor cells

2010/11-2012/13 • $135,000 • Scholarship/Fellowship,Other
Hematopoietic stem cells (HSCs) have the unique ability to give rise to all blood cell types and are thus indispensable for hematpoietic system development, homeostasis and repair. Normal HSC function critically depends on pronounced self-renewal capabilities, which make HSCs the preferred...

Stem Cell Network/Réseau de cellules souches

2010/11-2011/12 • $1,280,000 • PI,CO
No summary

Regulation of HSC self-renewal by bmi1 and associated proteins

2010/11-2011/12 • $242,559 • PI
Hemopoietic stem cells (HSC) are responsible for the transfer of a bone marrow cell graft between donors and recipients, a procedure called "bone marrow transplantation" and routinely used worldwide to cure a variety of blood cell diseases in humans. The ability of stem cells to divide almost...

Identification of murine embryonic stem cells fate determinants

2010/11-2011/12 • $70,000 • Scholarship/Fellowship,Other
Embryonic stem cells (ESC) are pluripotent, meaning that they can differentiate in almost every cell types of the organism. Critical genes and proteins are needed to allow differentiation. We have generated in our lab a library of ESC which contain chromosomal deletions, resulting in several...

Deciphering leukemogenesis through analysis of transcriptional complexes: The Meis-Prep model.

2010/11-2011/12 • $37,500 • Scholarship/Fellowship,Other
Leukemias are blood cancers characterized by an abnormal proliferation of blood cells that fail to complete their specialization process. The subsequent lack of functional cells (red blood cells, white blood cells, platelets...) will result in symptoms ranging from weakness, fever, bruising to...

CIHR Team in Stem Cell Expansion

2010/11 • $820,000 • PI,CO
¿Self-renewal¿ is a process central to the expansion of normal and cancerous stem cells and its understanding is critical for future advances in transplantation-based therapies and cancer treatment. Although the molecular machinery controlling self-renewal of hematopoietic stem cells (HSCs)...

Chaire de recherche du Canada en génétique moléculaire des cellules souches normales et concéreuses

2010/11 • $150,000 • PI
My research interests are to understand the molecular basis for a process called Self-Renewal which is central to the regulation of stem cells whether they are normal (e.g., blood stem cells, etc) or cancerous (e.g., leukemia). We have recently shown that tumor stem cells are uniquely dependent...

HoxB4 as a tool to characterize molecular regulators of HSC self renewal

2010/11 • $57,500 • PI,Other
Bone marrow transplantation (BMT) is a procedure where all the cellular component of the blood of a recipient are replaced with that of a donor. The potential of primitive cells, called hematopoietic stem cells (HSC), to divide and give rise to all the mature elements of the blood, renders the...

Functional in vivo screen of hematopoietic stem cell (HSC) self-renewal regulators

2010/11 • $12,500 • Scholarship/Fellowship,Other
«Self-renewal» is a crucial process for the expansion of normal and cancerous stem cells and its understanding is critical for future advances in transplantation-based therapies and cancer treatment. Even today, many patients are deprived of the benefit of a successful blood stem cell transplant...

Dissecting hematopoietic stem cell self-renewal with RNA interference

2010/11 • $3,333 • Scholarship/Fellowship,Other
Self-renewal is a specialized process whereby daughter cells inherit properties identical to those of the parent and is central to the regenerative capacity of all stem cells. As self-renewal is necessary for expansion of normal and neoplastic stem cells, its understanding is at the cornerstone...

Patents

PYRIMIDO[4,5-B]INDOLE DERIVATIVES AND USE THEREOF IN THE EXPANSION OF HEMATOPOIETIC STEM CELLS

Pyrimido[4,5-b]indole derivatives are provided. These compounds are useful to expand hematopoietic stem cell populations, particularly, human hematopoietic stem cell populations. The compounds are also useful in the medical treatment of diseases that involve hematopoietic stem cells.
Related applications: EP20130740815, PL20130740815T, HR2019P001189T, ES20130740815T, CA20132862140, EP20130740815, WO2013CA50052

METHODS TO MODULATE ACUTE MYELOID LEUKEMIA STEM/PROGENITOR CELL EXPANSION AND/OR DIFFERENTIATION

Novel methods for modulating acute myeloid leukemia stem/progenitor cell expansion and/or differentiation are disclosed. These methods are based on the use of aryl hydrocarbon receptor (AhR) modulators and/or compounds of formula I or II (see formula I) (see formula II) Screening assays to identify compounds that may be useful for inhibiting and/or eliminating AML initiating cells using AhR modulators and/or the compounds of formula I or ll are also disclosed. The use of pharmaceutically...
Related applications: CA20142848575

COMPOUNDS AND USE THEREOF IN THE EXPANSION OF HEMATOPOIETIC STEM CELLS AND/OR HEMATOPOIETIC PROGENITOR CELLS

Compounds of general formula or salts or prodrugs thereof, are provided and described herein. The compounds are useful to expand hematopoietic stem cell and/or hematopoietic progenitor cell populations. Particularly, the hematopoietic cells are human cells. The compounds are also useful in the medical treatment of hematopoietic disorder/malignancy, an autoimmune disease and/or an inherited immune-deficient disease in a subject.
Related applications: WO2015CA50330, EP20150782744, CA20152946446

COMPOUNDS AND METHODS FOR ENHANCING VIRAL GENE TRANSFER TO HUMAN HEMATOPOIETIC CELLS

Methods and compositions for enhancing viral gene transfer, such as lentiviral gene transfer, and improving the efficacy of gene delivery to cells such as primitive hematopoietic cells, are described. These methods and compositions are based on the use of pyrimido[4,5- b]indole derivatives. Cell-based compositions and methods useful for therapeutic indications amenable to treatment with gene therapies, including hematopoietic stem cell therapies, are also described.
Related applications: PL20150841193T, CA20152961535, WO2015CA50907, EP20150841193

PROGNOSTIC MARKERS OF ACUTE MYELOID LEUKEMIA SURVIVAL

Methods and kits for the diagnosis and prognosis of acute myeloid leukemia (AML) are described. These methods and kits are based on the assessment of the level of expression of the gene High Mobility Group AT-hook 2 (HMGA2), and optionally of the level of expression of at least one additional prognostic marker gene such as PRKC Apoptosis WT1 Regulator (PAWR), in a biological sample from an AML patient. High levels of expression of HMGA2 and PAWR in the sample are associated with poor disease...
Related applications: WO2016CA50562

SELECTION OF HUMAN HEMATOPOETIC STEM CELLS USING EPCR

It is provided a method of expanding ex vivo hematopoietic stem cells (HSC), the method comprising selecting a population of Endothelial Protein C Receptor (EPCR)+ HSC, culturing the selected HSC thereby expanding said EPCR+ HSC and the use of the expanded EPCR+ HSC for stem cells transplantation.
Related applications: EP20170805448, CA20173024273, WO2017CA50661

USE OF MITOCHONDRIAL ACTIVITY INHIBITORS FOR THE TREATMENT OF POOR PROGNOSIS ACUTE MYELOID LEUKEMIA

A method for treating acute myeloid leukemia (AML), such as poor risk AML, by administering to a subject in need thereof an effective amount of a mitochondrial activity inhibitor, for example a class A electron transport chain (ETC) complex I inhibitor such as Mubritinib or a pharmaceutically acceptable salt thereof, is disclosed. The AML to be treated may be characterized by certain features, such as high level of expression of one or more Homeobox (HOX)-network genes, high and/or low...
Related applications: EP20170836123, WO2017CA50921, CA20162937896, CA20173032470

HETEROCYCLIC MITOCHONDRIAL ACTIVITY INHIBITORS AND USES THEREOF

Heterocyclic compounds of Formula (I) and pharmaceutically acceptable salt thereof are disclosed. The use of such heterocyclic compounds and pharmaceutically acceptable salt thereof for the treatment of cancers, and more particularly cancers sensitive to mitochondrial activity inhibition and increased reactive oxygen species (ROS) levels, is also disclosed. Such cancers include acute myeloid leukemia (AML), preferably AML characterized by certain features, such as high level of expression of...
Related applications: CA20182995617, WO2018CA00206

COMPOUNDS AND USE THEREOF IN THE EXPANSION OF STEM CELLS AND/OR PROGENITOR CELLS

The invention relates to compounds of formula I and pharmaceutical compositions containing them. Also, the invention relates to methods for expanding stem cells and/or progenitor cells and methods for treating a hematopoietic disorder/malignancy, and autoimmune disease and/or an inherited immunodeficient disease (I).
Related applications: WO2018IB58593

EXPANSION OF NK AND DC CELLS IN VIVO MEDIATING IMMUNE RESPONSE

It is provided a method of expanding dendritic (DC) cells and/or natural killer (NK) cells in vivo in a patient comprising the steps of producing a graft of stem and progenitor cells cultured with UM171 or analogues therefrom and expanded before being administered to the patient. The expansion or increase in dendritic (DC) cells and/or natural killer (NK) cells population in the patient results in an increase immune response reducing transplant related mortality (TRM), severe...
Related applications: WO2019CA50208