A5012281611- Chromatin Remodeling and Cancer
- Advanced Breast Cancer Therapies
- Ferroptosis and cancer prognosis
- Radiomics and Machine Learning in Medical Imaging
- Epigenetics and DNA Methylation
- Lung Cancer Research Studies
- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- PI3K/AKT/mTOR signaling in cancer
- Microtubule and mitosis dynamics
- Cancer Mechanisms and Therapy
- Monoclonal and Polyclonal Antibodies Research
- Cancer therapeutics and mechanisms
- Cytokine Signaling Pathways and Interactions
- Cancer-related Molecular Pathways
- Cell Adhesion Molecules Research
- Fibroblast Growth Factor Research
- Synthesis and biological activity
- Chronic Lymphocytic Leukemia Research
- Neuroendocrine Tumor Research Advances
- HER2/EGFR in Cancer Research
- Pancreatic and Hepatic Oncology Research
- Click Chemistry and Applications
- Single-cell and spatial transcriptomics
- Ubiquitin and proteasome pathways
McGill University
2011-2025
McGill University Health Centre
2008-2023
Montreal Neurological Institute and Hospital
2015
Goodman (Japan)
2015
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 Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for breast cancer treatment and show activity against other malignancies, including KRAS-mutant non–small cell lung (NSCLC). However, the clinical efficacy of CDK4/6 is limited due to frequent drug resistance their largely cytostatic effects. Through a genome-wide cDNA screen, we identified that bromodomain-containing protein 4 (BRD4) overexpression conferred inhibitor palbociclib in NSCLC cells. Inhibition BRD4, either by...
We previously identified claudin-2 as a functional mediator of breast cancer liver metastasis. now confirm that levels are elevated in metastases, but not skin compared to their matched primary tumors patients with cancer. Moreover, is specifically expressed liver-metastatic cells populations derived from bone or lung metastases. The increased tropism exhibited by claudin-2-expressing requires claudin-2-mediated interactions between and hepatocytes. Furthermore, the reduction expression...
The small guanosine triphosphatase Rab13 functions in exocytic vesicle trafficking epithelial cells. Alterations activity have been observed human cancers, yet the mechanism of activation and its role cancer progression remain unclear. In this paper, we identify DENN domain protein DENND2B as guanine nucleotide exchange factor for develop a novel Förster resonance energy transfer–based Rab biosensor to reveal by at leading edge migrating interacts with effector MICAL-L2 cell periphery,...
Abstract Inactivating mutations in SMARCA4 and concurrent epigenetic silencing of SMARCA2 characterize subsets ovarian lung cancers. Concomitant loss these key subunits SWI/SNF chromatin remodeling complexes both cancers is associated with chemotherapy resistance poor prognosis. Here, we discover that SMARCA4/2 inhibits chemotherapy-induced apoptosis through disrupting intracellular organelle calcium ion (Ca 2+ ) release By restricting accessibility to ITPR3 , encoding Ca channel IP3R3,...
The non-receptor protein-tyrosine phosphatases (PTPs) 1B and T-cell phosphatase (TCPTP) have been implicated as negative regulators of multiple signaling pathways including receptor-tyrosine kinases. We identified PTP1B TCPTP the hepatocyte growth factor receptor, Met kinase. In vivo, loss or enhances factor-mediated phosphorylation Met. Using substrate trapping mutants TCPTP, we demonstrated that both interact with these interactions require twin tyrosines (Tyr-1234/1235) in activation loop...
Abstract Subsets of breast tumors present major clinical challenges, including triple-negative, metastatic/recurrent disease and rare histologies. Here, we developed 37 patient-derived xenografts (PDX) from these difficult-to-treat cancers to interrogate their molecular composition functional biology. Whole-genome transcriptome sequencing reverse-phase protein arrays revealed that PDXs conserve the landscape corresponding patient tumors. Metastatic potential varied between PDXs, where...
Abstract SMARCA4 (BRG1) and SMARCA2 (BRM) are the two paralogous ATPases of SWI/SNF chromatin remodeling complexes frequently inactivated in cancers. Cells deficient either ATPase have been shown to depend on remaining counterpart for survival. Contrary this paralog synthetic lethality, concomitant loss SMARCA4/2 occurs a subset cancers associated with very poor outcomes. Here, we uncover that SMARCA4/2-loss represses expression glucose transporter GLUT1, causing reduced uptake glycolysis...
Abstract Introduction CT10 regulator of kinase (Crk) adaptor proteins (CrkI, CrkII and CrkL) play a role in integrating signals for migration invasion highly malignant breast cancer cell lines. This has important implications, as elevated CrkI/II protein levels were observed small cohort patients, which identified potential Crk progression. Numerous vitro studies motility, but little is known about how contribute to progression vivo . Methods The clinical significance human was assessed by...
Understanding how inhibitors rewire the Met receptor pathway points to a strategy for more effective gastric cancer treatment.
CDK4/6 inhibitors are FDA-approved drugs for estrogen receptor-positive (ER+) breast cancer and being evaluated to treat other tumor types, including KRAS-mutant non-small cell lung (NSCLC). However, their clinical utility is often limited by drug resistance. Here, we sought better understand the resistant mechanisms help devise potential strategies overcome this challenge. We show that treatment with in both ER+ NSCLC cells induces feedback upregulation of cyclin D1, CDK4, E1, mediating...
Triple negative breast cancer (TNBC) is associated with poor prognosis and mainly treated chemotherapy-based regimens, often including carboplatin. Resistance to carboplatin a common clinical issue that either initially present or develops treatment. Overcoming this resistance significant challenge, which highlights the need for novel therapeutic strategies. We used pooled shRNA screening approach chemoresistant TNBC patient-derived xenograft (PDX) cell (PDXC) line identify targets whose...
Abstract Functional precision medicine (FPM) integrates patient-derived preclinical models, molecular profiling, and drug sensitivity testing to advance personalized cancer treatments. This approach uses live patient tumor samples conduct real-time functional assays, exposing them a range of therapeutic agents determine which treatments may be most effective. FPM enables more tailored potentially effective treatment strategy, particularly for complex cancers such as invasive breast...
Invadopodia are specialized membrane protrusions that support degradation of extracellular matrix (ECM) by cancer cells, allowing invasion and metastatic spread. Although early stages invadopodia assembly have been elucidated, little is known about maturation into structures competent for ECM proteolysis. The localized conversion phosphatidylinositol(3,4,5)-triphosphate accumulation phosphatidylinositol(3,4)-bisphosphate at a key determinant maturation. Here we investigate the role...
Receptor tyrosine kinases (RTKs) are recognized as targets of precision medicine in human cancer upon their gene amplification or constitutive activation, resulting increased downstream signal complexity including heterotypic crosstalk with other RTKs. The Met RTK exhibits such reciprocal several members the EGFR (HER) family RTKs when amplified cells. We show that signaling converges on HER3-tyrosine phosphorylation across a panel seven MET-amplified cell lines and HER3 is required for...
Abstract Triple-negative breast cancer (TNBC) is a heterogeneous disease that lacks both effective patient stratification strategies and therapeutic targets. Whilst elevated levels of the MET receptor tyrosine kinase are associated with TNBCs predict poor clinical outcome, functional role in TNBC still poorly understood. In this study, we utilise an established Met-dependent transgenic mouse model TNBC, human cell lines patient-derived xenografts to investigate tumorigenesis. We find...
<div>Abstract<p>Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for breast cancer treatment and show activity against other malignancies, including <i>KRAS</i>-mutant non–small cell lung (NSCLC). However, the clinical efficacy of CDK4/6 is limited due to frequent drug resistance their largely cytostatic effects. Through a genome-wide cDNA screen, we identified that bromodomain-containing protein 4 (BRD4) overexpression conferred inhibitor palbociclib in...
<div>Abstract<p>Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for breast cancer treatment and show activity against other malignancies, including <i>KRAS</i>-mutant non–small cell lung (NSCLC). However, the clinical efficacy of CDK4/6 is limited due to frequent drug resistance their largely cytostatic effects. Through a genome-wide cDNA screen, we identified that bromodomain-containing protein 4 (BRD4) overexpression conferred inhibitor palbociclib in...
Abstract Despite major advances in the treatment of breast cancer (BC), it remains most diagnosed and second deadliest among American women. BC consists distinct clinical subtypes, including estrogen receptor or HER2 receptor-positive triple-negative (TNBC) that lacks these receptors preventing use established precision therapies standard care neoadjuvant chemotherapy (NACT), followed by surgery, radiation emerging combinations with immunotherapy. While NACT is effective some patients, up to...
<p>List of common direct target genes BRD4 in KRAS-mutant NSCLC cells.</p>
<p>List of NSCLC cell lines with corresponding BRD4 mRNA levels and IC50 values for palbociclib.</p>
<p>List of supplementary data and Supplementary Figures 1-9.</p>
<div>Abstract<p>Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for breast cancer treatment and show activity against other malignancies, including <i>KRAS</i>-mutant non–small cell lung (NSCLC). However, the clinical efficacy of CDK4/6 is limited due to frequent drug resistance their largely cytostatic effects. Through a genome-wide cDNA screen, we identified that bromodomain-containing protein 4 (BRD4) overexpression conferred inhibitor palbociclib in...
<p>List of NSCLC cell lines with corresponding BRD4 mRNA levels and IC50 values for palbociclib.</p>