A5052644596- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Hematopoietic Stem Cell Transplantation
- Histone Deacetylase Inhibitors Research
- CRISPR and Genetic Engineering
- Multiple Myeloma Research and Treatments
- Pluripotent Stem Cells Research
- Retinoids in leukemia and cellular processes
- Epigenetics and DNA Methylation
- Lymphatic System and Diseases
- Immune Cell Function and Interaction
- Ubiquitin and proteasome pathways
- Hemoglobinopathies and Related Disorders
- T-cell and B-cell Immunology
- Cancer Genomics and Diagnostics
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- Immune cells in cancer
- Trace Elements in Health
- Acute Lymphoblastic Leukemia research
- RNA Interference and Gene Delivery
- Drug Transport and Resistance Mechanisms
- Cytokine Signaling Pathways and Interactions
- Hedgehog Signaling Pathway Studies
- RNA Research and Splicing
Université de Montréal
2013-2025
Institute for Research in Immunology and Cancer
2013-2025
In a phenotypical screen of 56 acute myeloid leukemia (AML) patient samples and using library 10,000 compounds, we identified hit with increased sensitivity toward
Transplantation of expanded hematopoietic stem cells (HSCs) and gene therapy based on HSC engineering have emerged as promising approaches for the treatment hematological diseases. Nevertheless, immunophenotype cultured HSCs remains poorly defined. Here, we identify Integrin-α3 (ITGA3) a marker human HSCs. Exploiting pyrimidoindole derivative UM171 to expand cord blood (CB) cells, show that ITGA3 expression is sufficient separate primitive EPCR+CD90+CD133+CD34+CD45RA- population into two...
Accurate quantification of gene expression by qRT-PCR relies on normalization against a consistently expressed control gene. However, genes in common use often vary greatly between samples, especially cancer. The advent Next Generation Sequencing technology offers the possibility to better select with least cell variability steady state transcript levels. Here we analyze transcriptomes 55 leukemia samples identify most consistent genes. This list is enriched for components proteasome (ex....
Purpose:RUNX1-mutated (RUNX1mut) acute myeloid leukemia (AML) is associated with adverse outcome, highlighting the urgent need for a better genetic characterization of this AML subgroup and design efficient therapeutic strategies disease. Toward goal, we further dissected mutational spectrum gene expression profile RUNX1mut correlated these results to drug sensitivity identify novel compounds targeting subgroup.Experimental Design: RNA-sequencing 47 primary specimens was performed sequencing...
Elucidation of the molecular cues required to balance adult stem cell self-renewal and differentiation is critical for advancing cellular therapies. Herein, we report that hematopoietic (HSC) agonist UM171 triggers a balanced pro- anti-inflammatory/detoxification network relies on NFKB activation protein C receptor-dependent ROS detoxification, respectively. We demonstrate within this network, EPCR serves as protective component its deletion hypersensitizes primitive cells pro-inflammatory...
In a functional genomics screen of mouse embryonic stem cells (ESCs) with nested hemizygous chromosomal deletions, we reveal that ribosomal protein (RP) genes are the most significant haploinsufficient determinants for embryoid body (EB) formation. Hemizygocity three RP (Rps5, Rps14, or Rps28), distinguished by proximity their corresponding to ribosome's mRNA exit site, is associated profound phenotype. This EB phenotype was fully rescued BAC cDNA complementation but not reduction p53...
Abstract In efforts to identify additional therapeutic targets for Acute Myeloid Leukemia (AML), we performed a high-throughput screen that includes 56 primary specimens tested with 10,000 structurally diverse small molecules. One specific hit, called S656 acts as molecular glue degrader (MGD), mediates the CRL4-dependent proteolysis of cyclin K. Structurally, features moiety binds ATP binding site cyclin-dependent kinases (CDKs), allowing recruitment CDK12-cyclin K complex, along DDB1...
Immunotherapies in acute myeloid leukemia (AML) are limited by shared antigen expression between leukemic and healthy hematopoietic cells, leading to on-target toxicity. Here we developed a clinically scalable strategy engineer cord blood (CB)-derived stem progenitor cell (HSPC) grafts resistant CD33-directed therapies. Leveraging UM171-mediated expansion adenine base editing, precisely disrupted critical epitope CD33 required for gemtuzumab ozogamicin (GO) binding, centered on phenylalanine...
High-mobility group AT-hook 2 (HMGA2) is a nonhistone chromatin-binding protein that normally expressed in stem cells of various tissues and aberrantly detected several tumor types. We recently observed one-fourth human acute myeloid leukemia (AML) specimens express HMGA2, which associates with very poor prognosis. present results indicating HMGA2+ AMLs share distinct transcriptional signature representing an immature phenotype. Using single-cell analyses, we showed HMGA2 CD34+ subsets early...
The cystatin protein superfamily is characterized by the presence of conserved sequences that display cysteine protease inhibitory activity (e.g., towards cathepsins). Type 1 and 2 cystatins are encoded 25 genes which 23 grouped in clusters localized on mouse chromosomes 16 2. expression essential roles most these development hematopoiesis remain poorly characterized. In this study, we describe a set quantitative real-time PCR assays global profile normal tissues. Benefiting from our...
Understanding the function of important DNA elements in mammalian stem cell genomes would be enhanced by availability deletion collections which segmental haploidies are precisely characterized. Using a modified Cre-loxP-based system, we now report creation and characterization collection ∼1,300 independent embryonic (ESC) clones enriched for nested chromosomal deletions. Mapping experiments indicate that this spans over 25% mouse genome with good representative coverage protein-coding...
Cholesterol homeostasis has been proposed as one mechanism contributing to chemoresistance in AML and hence, inclusion of statins therapeutic regimens part clinical trials shown encouraging results. Chemical screening primary human specimens by our group led the identification lipophilic potent inhibitors AMLs from a wide range cytogenetic groups. Genetic identify modulators statin response uncovered role protein geranylgeranylation RAB proteins, coordinating various aspect vesicular...