A5021226937- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Epigenetics and DNA Methylation
- Hemoglobinopathies and Related Disorders
- Peptidase Inhibition and Analysis
- Virus-based gene therapy research
- Biochemical and Molecular Research
- Microbial Natural Products and Biosynthesis
- Genomics and Chromatin Dynamics
- Extracellular vesicles in disease
- RNA Interference and Gene Delivery
- Phagocytosis and Immune Regulation
- Acute Lymphoblastic Leukemia research
- Carbohydrate Chemistry and Synthesis
- Plant biochemistry and biosynthesis
- interferon and immune responses
- Cancer Genomics and Diagnostics
- Microfinance and Financial Inclusion
- Enzyme Production and Characterization
- Immune cells in cancer
- Cancer Research and Treatments
- Single-cell and spatial transcriptomics
Dana-Farber Cancer Institute
2023-2024
Harvard University
2023-2024
Boston Children's Hospital
2023-2024
McGill University
2016-2022
Ottawa Hospital Research Institute
2015-2022
McGill University Health Centre
2015-2022
Ottawa Hospital
2015-2022
Concordia University
2019
University of Ottawa
2014
Therapy for acute myeloid leukemia (AML) involves intense cytotoxic treatment and yet approximately 70% of AML are refractory to initial therapy or eventually relapse. This is at least partially driven by the chemo-resistant nature leukemic stem cells (LSCs) that sustain disease, therefore novel anti-LSC therapies could decrease relapses improve survival. We performed in silico analysis highly prognostic human LSC gene expression signatures using existing datasets drug-gene interactions...
Abstract Recent advances in cancer therapeutics clearly demonstrate the need for innovative multiplex therapies that attack tumour on multiple fronts. Oncolytic or “cancer-killing” viruses (OVs) represent up-and-coming multi-mechanistic immunotherapeutic drugs treatment of cancer. In this study, we perform an in-vitro screen based virus-encoded artificial microRNAs (amiRNAs) and find a unique amiRNA, herein termed amiR-4, confers replicative advantage to VSVΔ51 OV platform. Target validation...
Abstract Our ability to manage acute myeloid leukemia (AML) is limited by our incomplete understanding of the epigenetic disruption central leukemogenesis, including improper histone methylation. Here we examine 16 H3 genes in 434 primary AML samples and identify Q69H, A26P, R2Q, R8H K27M/I mutations (1.6%), with higher incidence secondary (9%). These occur pre-leukemic hematopoietic stem cells (HSCs) exist major leukemic clones patients. They increase frequency functional HSCs, alter...
Cardiac glycosides are approved for the treatment of heart failure as Na+/K+ pump inhibitors. Their repurposing in oncology is currently investigated preclinical and clinical studies. However, identification a specific cancer type defined by molecular signature to design targeted trials with cardiac remains be characterized. Here, we demonstrate that glycoside proscillaridin A specifically targets MYC overexpressing leukemia cells stem causing degradation, epigenetic reprogramming...
Abstract Bacterial polyketides are a rich source of chemical diversity and pharmaceutical agents. Understanding the biochemical basis for their biosynthesis evolutionary driving force leading to this is essential take advantage enzymes as biocatalysts access new drug discovery. Biochemical characterization thioesterase (TE) responsible 6‐deoxyerythronolide macrocyclization shows that small, evolutionarily accessible change substrate can increase products, including macrodiolide formation. We...
Abstract Clonal hematopoiesis (CH) is a common premalignant state in the blood and confers an increased risk of cancers all-cause mortality. Identification therapeutic targets CH has been hindered by lack ex vivo platform amenable for studying primary hematopoietic stem progenitor cells (HSPCs). Here, we utilize co-culture system HSPCs with bone marrow endothelial to perform CRISPR/Cas9 screens mutant HSPCs. Our data reveal that loss histone demethylase family members Kdm3b Jmjd1c...
<p>Ex vivo characterization of BMEC/HSPC co-cultures</p>
<p>CRISPR screens in Dnmt3a- and Asxl1-mutant HSPCs Jmjd1c dependency Idh2- Tet2-mutant HSPCs</p>
<div>Abstract<p>Clonal hematopoiesis (CH) is a common premalignant state in the blood and confers an increased risk of cancers all-cause mortality. Identification therapeutic targets CH has been hindered by lack <i>ex vivo</i> platform amenable for studying primary hematopoietic stem progenitor cells (HSPCs). Here, we utilize co-culture system HSPCs with bone marrow endothelial to perform CRISPR/Cas9 screens mutant HSPCs. Our data reveal that loss histone demethylase...
<p>In vivo validation of Kdm3b dependency</p>
<p>Role of 2-HG and KDM3B catalytic activity in dependency</p>
<p>Chromatin and transcriptional changes mediated by KDM3B</p>
<p>Effects on TPO, GM-CSF, and ruxolitinib Idh2R140Q HSPCs</p>
<p>Development of CRISPR screens with BMEC/HSPC co-cultures</p>
<p>Validation of KDM3B and JMJD1C dependencies in human HSPCs Tet2-/-Npm1cAFlt3ITD leukemia model</p>
<p>In vivo validation of Jmjd1c dependency</p>