A5082063704- Immune cells in cancer
- Ferroptosis and cancer prognosis
- Cancer Immunotherapy and Biomarkers
- Chromatin Remodeling and Cancer
- Immunotherapy and Immune Responses
- Salivary Gland Tumors Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Advanced Breast Cancer Therapies
- Lung Cancer Research Studies
- Neuroendocrine Tumor Research Advances
- Radiomics and Machine Learning in Medical Imaging
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- Lung Cancer Treatments and Mutations
- Peptidase Inhibition and Analysis
- Glioma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Neuroblastoma Research and Treatments
- Osteoarthritis Treatment and Mechanisms
- Cell Adhesion Molecules Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nanoplatforms for cancer theranostics
- Cancer Cells and Metastasis
- Protease and Inhibitor Mechanisms
- Cancer-related gene regulation
McGill University
2019-2025
McGill University Health Centre
2019-2025
Cancer Institute (WIA)
2024
HEC Montréal
2023
Centre For Human Genetics
2023
Concordia University
2019
Memorial Sloan Kettering Cancer Center
2012-2017
Royal Liverpool University Hospital
2002-2016
University of Liverpool
2002-2016
Kettering University
2015
Immune checkpoint inhibitors are effective cancer treatments, but molecular determinants of clinical benefit unknown. Ipilimumab and tremelimumab antibodies against cytotoxic T-lymphocyte antigen 4 (CTLA-4). Anti-CTLA-4 treatment prolongs overall survival in patients with melanoma. CTLA-4 blockade activates T cells enables them to destroy tumor cells.We obtained tissue from melanoma who were treated ipilimumab or tremelimumab. Whole-exome sequencing was performed on tumors matched blood...
Targeting the dynamic tumor immune microenvironment (TIME) can provide effective therapeutic strategies for cancer. Neutrophils are predominant leukocyte population in mice and humans, mounting evidence implicates these cells during growth metastasis. Neutrophil extracellular traps (NETs) networks of neutrophil DNA fibers that capable binding to support metastatic progression. Here, we demonstrate circulating NET levels elevated advanced esophageal, gastric, lung cancer patients compared...
Abstract Single-cell technologies have enabled the characterization of tumour microenvironment at unprecedented depth and revealed vast cellular diversity among cells their niche. Anti-tumour immunity relies on cell–cell relationships within 1,2 , yet many single-cell studies lack spatial context rely dissociated tissues 3 . Here we applied imaging mass cytometry to characterize immunological landscape 139 high-grade glioma 46 brain metastasis tumours from patients. analysis more than 1.1...
Abstract Single-cell technologies have revealed the complexity of tumour immune microenvironment with unparalleled resolution 1–9 . Most clinical strategies rely on histopathological stratification subtypes, yet spatial context single-cell phenotypes within these stratified subgroups is poorly understood. Here we apply imaging mass cytometry to characterize and immunological landscape samples from 416 patients lung adenocarcinoma across five histological patterns. We resolve more than 1.6...
Abstract Purpose: Salivary duct carcinoma (SDC) is an aggressive salivary malignancy, which resistant to chemotherapy and has high mortality rates. We investigated the molecular landscape of SDC, focusing on genetic alterations gene expression profiles. Experimental Design: performed whole-exome sequencing, RNA immunohistochemical analyses in 16 SDC tumors examined selected via targeted sequencing 410 genes a second cohort 15 SDCs. Results: SDCs harbored higher mutational burden than many...
Glioblastomas are aggressive primary brain tumors with an inherent resistance to T cell-centric immunotherapy due their low mutational burden and immunosuppressive tumor microenvironment. Here we report that fractionated radiotherapy of preclinical glioblastoma models induce a tenfold increase in cell content. Orthogonally, spatial imaging mass cytometry shows enrichment human recurrent compared matched glioblastoma. In glioblastoma-bearing mice, α-PD-1 treatment applied at the peak...
Epigenetic alterations are associated with all aspects of cancer, from tumor initiation to cancer progression and metastasis. It is now well understood that both losses gains DNA methylation as altered chromatin organization contribute significantly cancer-associated phenotypes. More recently, new sequencing technologies have allowed the identification driver mutations in epigenetic regulators, providing a mechanistic link between epigenome genetic alterations. Oncogenic activating known...
At the root of most fatal malignancies are aberrantly activated transcriptional networks that drive metastatic dissemination. Although individual metastasis-associated genes have been described, complex regulatory presiding over initiation and maintenance tumors still poorly understood. There is untapped value in identifying therapeutic targets broadly govern coordinated modules dictating progression. Here, we reverse engineered interrogated a breast cancer-specific interaction network...
Myoepithelial carcinoma (MECA) is an aggressive salivary gland cancer with largely unknown genetic features. Here we comprehensively analyze molecular alterations in 40 MECAs using integrated genomic analyses. We identify a low mutational load, and high prevalence (70%) of oncogenic gene fusions. Most fusions involve the PLAG1 oncogene, which associated overexpression. find FGFR1-PLAG1 seven (18%) cases, novel TGFBR3-PLAG1 fusion six (15%) cases. promotes tumorigenic phenotype vitro, absent...
Immunotherapy has revolutionized clinical outcomes for patients suffering from lung cancer, yet relatively few sustain long-term durable responses. Recent studies have demonstrated that the tumor immune microenvironment fosters tumorous heterogeneity and mediates both disease progression response to checkpoint inhibitors (ICI). As such, there is an unmet need elucidate spatially defined single-cell landscape of cancer understand mechanisms identify biomarkers ICI.Here, in this study, we...
Obesity is characterized by chronic systemic inflammation and enhances cancer metastasis mortality. promotes breast to lung in a neutrophil-dependent manner; however, the upstream regulatory mechanisms of this process remain unknown. Here, we show that obesity-induced monocytes underlie neutrophil activation metastasis. Using mass cytometry, obesity favors expansion myeloid lineages while restricting lymphoid cells within peripheral blood. RNA sequencing flow cytometry revealed...
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...
Abstract Background Pain from osteoarthritis (OA) is one of the top causes disability worldwide, but effective treatment lacking. Nociceptive factors are released by activated synovial macrophages in OA, depletion paradoxically worsens inflammation and tissue damage previous studies. Rather than depleting macrophages, we hypothesized that inhibiting macrophage activation may improve pain without increasing damage. We aimed to identify key mechanisms mediating test role STAT signaling on...
TGF-β signaling has been extensively studied in many developmental contexts, amongst which is its ability to induce epithelial mesenchymal transitions (EMT). EMTs play crucial roles during embryonic development and have also come under intense scrutiny as a mechanism through breast cancers progress become metastatic. Interestingly, while the molecular hallmarks of EMT progression (loss cell adhesion, nuclear localization β-catenin) are straightforward, cellular cascades that result an...