A5059999035- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Advanced Breast Cancer Therapies
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- Wnt/β-catenin signaling in development and cancer
- Cancer Mechanisms and Therapy
- Melanoma and MAPK Pathways
- Immune cells in cancer
- Ferroptosis and cancer prognosis
- MicroRNA in disease regulation
- Chromatin Remodeling and Cancer
- Acute Lymphoblastic Leukemia research
- Metabolism, Diabetes, and Cancer
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Immune Cell Function and Interaction
- Cancer-related Molecular Pathways
- Phagocytosis and Immune Regulation
- Acute Myeloid Leukemia Research
- Health Systems, Economic Evaluations, Quality of Life
- Mechanisms of cancer metastasis
- Telomeres, Telomerase, and Senescence
- Connective Tissue Growth Factor Research
Gilead Sciences (United States)
2023-2024
McGill University Health Centre
2016-2022
McGill University
2017-2020
Occupational Cancer Research Centre
2019
Goodman (Japan)
2019
Montreal Children's Hospital
2018
Institute for Research in Immunology and Cancer
2016
Université de Montréal
2016
Hospital for Sick Children
2011-2014
University of Toronto
2010-2012
Understanding the tumor immune microenvironment (TIME) promises to be key for optimal cancer therapy, especially in triple-negative breast (TNBC). Integrating spatial resolution of cells with laser capture microdissection gene expression profiles, we defined distinct TIME stratification TNBC, implications current therapies including checkpoint blockade. TNBCs an immunoreactive exhibited tumoral infiltration granzyme B+CD8+ T (GzmB+CD8+ cells), a type 1 IFN signature, and elevated multiple...
Epigenetic modifications on DNA and histones regulate gene expression by modulating chromatin accessibility to transcription machinery. Here we identify methionine as a key nutrient affecting epigenetic reprogramming in CD4+ T helper (Th) cells. Using metabolomics, showed that is rapidly taken up activated cells serves the major substrate for biosynthesis of universal methyl donor S-adenosyl-L-methionine (SAM). Methionine was required maintain intracellular SAM pools restriction reduced...
Rapid and efficient protocols to generate oligodendrocytes (OL) from human induced pluripotent stem cells (iPSC) are currently lacking, but may be a key technology understand the biology of myelin diseases develop treatments for such disorders. Here, we demonstrate that induction three transcription factors (SOX10, OLIG2, NKX6.2) in iPSC-derived neural progenitor is sufficient rapidly O4+ OL with an efficiency up 70% 28 d global gene-expression profile comparable primary OL. We further...
Neutrophils are phenotypically heterogeneous and exert either anti- or pro-metastatic functions. We show that cancer-cell-derived G-CSF is necessary, but not sufficient, to mobilize immature low-density neutrophils (iLDNs) promote liver metastasis. In contrast, mature high-density inhibit the formation of metastases. Transcriptomic metabolomic analyses high- reveal engagement numerous metabolic pathways specifically in neutrophils. iLDNs exhibit enhanced global bioenergetic capacity, through...
Abstract Elevated production of collagen-rich extracellular matrix is a hallmark cancer-associated fibroblasts (CAFs) and central driver cancer aggressiveness. Here we find that proline, highly abundant amino acid in collagen proteins, newly synthesized from glutamine CAFs to make tumour breast xenografts. PYCR1 key enzyme for proline synthesis expressed the stroma patients CAFs. Reducing levels sufficient reduce production, growth metastatic spread vivo cell proliferation vitro. Both...
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AXL is activated by its ligand GAS6 and expressed in triple-negative breast cancer cells. In the current study, we report expression HER2-positive (HER2+) cancers where it correlates with poor patient survival. Using murine models of HER2+ cancer, Axl, but not Gas6, was found to be essential for metastasis. We determined that required intravasation, extravasation, growth at metastatic site. displaying epithelial-to-mesenchymal transition (EMT) signatures contributes sustain EMT. Interfering...
Abstract Inactivating mutations in SMARCA4 ( BRG1 ), a key SWI/SNF chromatin remodelling gene, underlie small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). To reveal its druggable vulnerabilities, we perform kinase-focused RNAi screens and uncover that SMARCA4-deficient SCCOHT cells are highly sensitive to inhibition cyclin-dependent kinase 4/6 (CDK4/6). loss causes profound downregulation cyclin D1, which limits CDK4/6 activity leads vitro vivo susceptibility inhibitors. patient...
Abstract Emerging evidence has illustrated the importance of epigenomic reprogramming in cancer, with altered post-translational modifications histones contributing to pathogenesis. However, contributions histone modifiers breast cancer progression are unclear, and how these processes vary between molecular subtypes yet be adequately addressed. Here we report that genetic or pharmacological targeting epigenetic modifier Ezh2 dramatically hinders metastatic behaviour both a mouse model...
Triple negative breast cancer (TNBC) is aggressive with limited treatment options upon recurrence. Molecular discordance between primary and metastatic TNBC has been observed, but the degree of biological heterogeneity not fully explored. Furthermore, genomic evolution through poorly understood. In this study, we aim to characterize changes paired TNBCs transcriptomic profiling, identify alterations which may contribute chemotherapy resistance. Genomic mRNA expression 10 were determined...
Germline mutations in STK11, which encodes the tumor suppressor liver kinase B1 (LKB1), promote Peutz-Jeghers syndrome (PJS), a cancer predisposition characterized by development of gastrointestinal (GI) polyps. Here, we report that heterozygous deletion Stk11 T cells (LThet mice) is sufficient to GI polyposis. Polyps from LThet mice, Stk11+/- and human PJS patients display hallmarks chronic inflammation, marked inflammatory immune-cell infiltration, signal transducer activator transcription...
Abstract Claudin-2 promotes breast cancer liver metastasis by enabling seeding and early cell survival. We now demonstrate that is functionally required for colorectal expression in primary cancers associated with poor overall metastasis-free have examined the role of Claudin-2, other claudin family members, as potential prognostic biomarkers desmoplastic replacement histopathological growth pattern metastases. Immunohistochemical analysis revealed higher levels type metastases when compared...
Abstract The role of the stromal compartment in tumor progression is best illustrated breast cancer bone metastases, where supports growth, albeit through poorly defined mechanisms. p38MAPKα frequently expressed cells and surrounding cells, its expression levels correlate with poor prognosis. This observation led us to investigate whether inhibition could reduce metastases a clinically relevant model. Orally administered, small-molecule inhibitors or downstream kinase MK2 each limited...
Triple-negative breast cancers (TNBCs) display a complex spectrum of mutations and chromosomal aberrations. Chromosome 5q (5q) loss is detected in up to 70% TNBCs, but little known regarding the genetic drivers associated with this event. Here, we show somatic deletion region syntenic human 5q33.2–35.3 mouse model TNBC. Mechanistically, identify KIBRA as major factor contributing effects on tumor growth metastatic progression. Re-expression impairs metastasis vivo inhibits tumorsphere...
Abstract Most colorectal (CRC) tumors are dependent on EGFR/KRAS/BRAF/MAPK signaling activation. ARID1A is an epigenetic regulator mutated in approximately 5% of non-hypermutated CRC tumors. Here we show that anti-EGFR but not anti-VEGF treatment enriches for emerging mutations patients. In addition, find patients with mutations, at baseline, associated worse outcome when treated cetuximab- bevacizumab-containing therapies; thus, this suggests may provide both acquired and intrinsic...
Abstract Introduction: Despite advances in targeted and IO therapies, lung adenocarcinoma (LUAD) remains a high unmet clinical need due to its complex molecular landscape. Previous studies have focused on early-stage disease with smaller patient populations identify subtypes LUAD. This study characterized the profiles features of LUAD tumors from large real-world dataset (RWD) containing early late-stage patients as well primary metastatic sites. Methods: The analysis cohort consisted...
Degeneration of oligodendroglial distal processes has been identified as an early event in multiple sclerosis (MS) lesion development. Our objective was to further define the development "dying-back" oligodendrocyte situ and model potential reversibility such responses using dissociated cultures adult human brain-derived oligodendrocytes.In analyses were performed on glutaraldehyde-fixed thin sections clinically acute pathologically active cases MS. In vitro studies conducted...