A5086117748- Cancer, Hypoxia, and Metabolism
- Metabolism, Diabetes, and Cancer
- Cancer, Lipids, and Metabolism
- Endometrial and Cervical Cancer Treatments
- Metabolomics and Mass Spectrometry Studies
- Estrogen and related hormone effects
- Pharmacogenetics and Drug Metabolism
- Mercury impact and mitigation studies
- Epigenetics and DNA Methylation
- Metastasis and carcinoma case studies
- Cancer Research and Treatments
- Cancer Risks and Factors
- Cancer Cells and Metastasis
- Mathematical Biology Tumor Growth
- ATP Synthase and ATPases Research
- RNA modifications and cancer
- Caveolin-1 and cellular processes
- Glycosylation and Glycoproteins Research
- Human Health and Disease
- Fluoride Effects and Removal
- Indigenous Studies and Ecology
- Mitochondrial Function and Pathology
- Diet, Metabolism, and Disease
- Peroxisome Proliferator-Activated Receptors
- Menopause: Health Impacts and Treatments
University of Ottawa
2020-2024
Centre hospitalier universitaire de Québec
2016-2022
Université Laval
2016-2022
Ottawa Institute of Systems Biology
2021
Mitochondrial dynamics orchestrate many essential cellular functions, including metabolism, which is instrumental in promoting cancer growth and metastatic progression. However, how mitochondrial influences progression remains poorly understood. Here, we show that breast cells with low potential exhibit a more fused network compared to highly cells. To study the impact of on metastasis, promoted elongation by individual genetic deletion three key regulators fission (Drp1, Fis1, Mff) or...
Chemotherapy resistance is a critical barrier in cancer treatment. Metabolic adaptations have been shown to fuel therapy resistance; however, little known regarding the generality of these changes and whether specific therapies elicit unique metabolic alterations. Using combination metabolomics, transcriptomics, functional genomics, we show that two anthracyclines, doxorubicin epirubicin, distinct primary vulnerabilities human breast cells. Doxorubicin-resistant cells rely on glutamine drive...
Endometrial cancer (EC) is the most frequent gynecological in developed countries. Most EC occurs after menopause and diagnosed as endometrioid (type I) carcinomas, which exhibit a favorable prognosis. In contrast, non-endometrioid II) carcinomas such serous tumors have poor Our goal was to identify novel blood-based markers associated with subtypes recurrence surgery postmenopausal women. Using mass spectrometry-based untargeted metabolomics, we examined preoperative serum metabolites among...
Metabolic rewiring is essential for tumor growth and progression to metastatic disease, yet little known regarding how cancer cells modify their acquired metabolic programs in response different microenvironments. We have previously shown that liver-metastatic breast adopt an intrinsic program characterized by increased HIF-1α activity dependence on glycolysis. Here, we confirm vivo stable isotope tracing analysis (SITA) retain a glycolytic profile when grown as mammary tumors or liver...
Maintenance of cellular homeostasis and xenobiotic detoxification is mediated by 19 human UDP-glucuronosyltransferase enzymes (UGTs) encoded ten genes that comprise the glucuronidation pathway. Deep RNA sequencing major metabolic organs exposes a substantial expansion UGT transcriptome alternative splicing, with variants representing 20% to 60% canonical transcript expression. Nearly fifth expressed in-frame sequences may create distinct structural functional features. Follow-up cell-based...
The Inuit population of Nunavik (Northern Quebec, Canada) is highly exposed to persistent organic pollutants (POPs) through their traditional diet. Some POPs, i.e., hydroxylated metabolites polychlorinated biphenyls (OH-PCBs), pentachlorophenol (PCP), and perfluorooctane sulfonate (PFOS), compete with thyroxin (T4) for binding sites on transthyretin (TTR), a T4 transport protein found in plasma cerebrospinal fluid. We tested the hypothesis that these TTR-binding compounds decrease...
Alternative splicing at the human glucuronosyltransferase 1 gene locus (<i>UGT1</i>) produces alternate isoforms UGT1A_i2s that control glucuronidation activity through protein-protein interactions. Here, we hypothesized function as a complex protein network connecting other metabolic pathways with an influence on cancer cell metabolism. This is based pathway enrichment analysis of proteomic data identified several high-confidence candidate interaction proteins UGT1A_i2 in tissues—namely,...
The conjugative metabolism mediated by UDP-glucuronosyltransferase enzymes (UGTs) significantly influences the bioavailability and biological responses of endogenous molecule substrates xenobiotics including drugs. UGTs participate in regulation cellular homeostasis limiting stress induced toxic molecules, controlling hormonal signaling networks. Glucuronidation is highly regulated at genomic, transcriptional, post-transcriptional post-translational levels. However, UGT protein interaction...
In solid tumors, drug concentrations decrease with distance from blood vessels. However, cellular adaptations accompanying the gradated exposure of cancer cells to drugs are largely unknown. Here, we modeled spatiotemporal changes promoting chemotherapy resistance in breast cancer. Using pairwise cell competition assays at each step during acquisition chemoresistance, reveal an important priming phase that renders previously exposed sublethal refractory dose escalation. Therapy-resistant...
The detoxification enzyme UDP-glucuronosyltransferase UGT2B10 is specialized in the N-linked glucuronidation of many drugs and xenobiotics. Preferred substrates possess tertiary aliphatic amines heterocyclic amines, such as tobacco carcinogens several antidepressants antipsychotics. We hypothesized that alternative splicing (AS) constitutes a means to regulate steady-state levels activity. established transcriptome <i>UGT2B10</i> normal tumoral tissues multiple individuals. highest...
Nucleotide sugar-dependent glycosyltransferases (UGTs) are critical to the homeostasis of endogenous metabolites and detoxification xenobiotics. Their impact on cell metabolome remains unknown. Cellular metabolic changes resulting from human UGT expression were profiled by untargeted metabolomics. The abundant UGT1A1 UGT2B7 studied as prototypes along with their alternative (alt.) splicing-derived isoforms displaying structural differences. Nineteen biochemical routes modified, beyond known...
Abstract Endometrial cancer (EC) is the most frequent of female genital tract in developed countries. Most EC occurs after menopause and are diagnosed as endometrioid type I carcinomas that exhibit a favorable prognosis especially for grades 1 2. In contrast, II non-endometrioid such serous tumors have poor prognosis. The use small molecule biomarkers may facilitate accurate diagnosis prognostic predictions. Our goal was to identify novel blood-based markers associated with subtypes...