A5002016876- Erythrocyte Function and Pathophysiology
- Drug Transport and Resistance Mechanisms
- RNA modifications and cancer
- Pharmacogenetics and Drug Metabolism
- Hemoglobinopathies and Related Disorders
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related molecular mechanisms research
- Cancer therapeutics and mechanisms
- Heat shock proteins research
- Chronic Lymphocytic Leukemia Research
- Redox biology and oxidative stress
- Endoplasmic Reticulum Stress and Disease
- Cancer-related gene regulation
- RNA and protein synthesis mechanisms
- Acute Lymphoblastic Leukemia research
- Hedgehog Signaling Pathway Studies
- Iron Metabolism and Disorders
- Amino Acid Enzymes and Metabolism
- Urticaria and Related Conditions
- Gout, Hyperuricemia, Uric Acid
- Heme Oxygenase-1 and Carbon Monoxide
- Protein Degradation and Inhibitors
Institute for Research in Immunology and Cancer
2019-2024
Université de Montréal
2019-2024
Polytechnique Montréal
2023
Jewish General Hospital
2009-2015
McGill University
2010-2015
Methyl-7-guanosine (m7G) "capping" of coding and some noncoding RNAs is critical for their maturation subsequent activity. Here, we discovered that eukaryotic translation initiation factor 4E (eIF4E), itself a cap-binding protein, drives the expression capping machinery increased efficiency ∼100 RNAs. To quantify this, developed enzymatic (cap quantification; CapQ) quantitative cap immunoprecipitation (CapIP) methods. The CapQ method has further advantage it captures information about status...
Drug resistance underpins poor outcomes in many malignancies including refractory and relapsed acute myeloid leukemia (R/R AML). Glucuronidation is a common mechanism of drug inactivation impacting AML therapies, e.g., cytarabine, decitabine, azacytidine venetoclax. In cells, the capacity for glucuronidation arises from increased production UDP-glucuronosyltransferase 1A (UGT1A) enzymes. UGT1A elevation was first observed patients who after response to ribavirin, used target eukaryotic...
Cancer therapies are plagued by resistance. Previously, we discovered a novel form of cancer drug resistance where the Glioma-associated protein 1 (GLI1) elevates UGT1A glucuronidation enzymes, thereby glucuronidating cytarabine and ribavirin, leading to in leukemia patients. Here, demonstrate that GLI1 imparts ∼40 compounds, including FDA-approved drugs with disparate chemotypes (e.g., methotrexate venetoclax). indirectly UGT1As via chaperone calreticulin, which is required for Further,...
Late-stage erythroid cells synthesize large quantities of haemoglobin, a process requiring the co-ordinated regulation globin and haem synthesis as well iron uptake. In present study, we investigated role ERK (extracellular-signal-regulated kinase) p38 MAPK (mitogen-activated protein signalling pathways in MEL (mouse erythroleukaemia) cell differentiation. We found that treatment HMBA (hexamethylene bisacetamide)-induced with pathway inhibitor UO126 results an increase intracellular...
The UDP glucuronosyltransferases (UGT) deactivate many therapeutics via glucuronidation while being required for clearance of normal metabolites and xenobiotics. There are 19 UGT enzymes categorized into UGT1A UGT2B families based on sequence conservation. This presents a challenge in terms targeting specific UGTs to overcome drug resistance without eliciting overt toxicity. Here, we identified the first time that UGT1A4 is highly elevated acute myeloid leukemia (AML) patients its reduction...
Abstract Acute myeloid leukemia (AML) remains with dismal outcomes, mostly attributed to the inability of therapies eliminate stem cells (LSCs) leading relapse. LSCs home bone marrow (BM) niche where they maintain their quiescence state once in contact mesenchymal stromal (MSCs). Therefore, understanding what controls AML-niche interactions could lead therapeutic approaches that can prevent First, we implemented a novel 3D vitro system mimic human interactions. This structure consists...