A5068526019- Glioma Diagnosis and Treatment
- Axon Guidance and Neuronal Signaling
- CAR-T cell therapy research
- Cancer Cells and Metastasis
- Cancer Mechanisms and Therapy
- Cancer Genomics and Diagnostics
- MicroRNA in disease regulation
- 3D Printing in Biomedical Research
- Monoclonal and Polyclonal Antibodies Research
- Epigenetics and DNA Methylation
- Cell Image Analysis Techniques
- Polyomavirus and related diseases
- CRISPR and Genetic Engineering
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Immunotherapy and Immune Responses
- Reproductive System and Pregnancy
- Cancer Research and Treatments
- Phagocytosis and Immune Regulation
- Hedgehog Signaling Pathway Studies
- Single-cell and spatial transcriptomics
- Nanoplatforms for cancer theranostics
- 14-3-3 protein interactions
- Immune cells in cancer
- DNA Repair Mechanisms
McMaster University
2016-2025
BC Cancer Agency
2016
Lawrence Berkeley National Laboratory
2016
Glioblastoma (GBM) patients suffer from a dismal prognosis, with standard of care therapy inevitably leading to therapy-resistant recurrent tumors. The presence cancer stem cells (CSCs) drives the extensive heterogeneity seen in GBM, prompting need for novel therapies specifically targeting this subset tumor-driving cells. Here, we identify CD70 as potential therapeutic target GBM CSCs.
The reported risk factors for glioblastoma (GBM), i.e., ionizing radiation, Li-Fraumeni syndrome, Neurofibromatosis I, and Turcot also increase the of other brain tumor types. Risk human GBM are associated with different oncogenic mutation profiles. Pedigreed domestic dogs a shorter nose flatter face (brachycephalic dogs) display relatively high rates glioma formation. genetic profiles canine gliomas idiosyncratic. association putatively mutational patterns in humans canines suggests that...
Abstract Glioblastoma (GBM) carries a dismal prognosis and inevitably relapses despite aggressive therapy. Many members of the Eph receptor tyrosine kinase (EphR) family are expressed by GBM stem cells (GSC), which have been implicated in resistance to In this study, we identify several EphRs that mark therapeutically targetable GSC population treatment-refractory, recurrent (rGBM). Using highly specific EphR antibody panel CyTOF (cytometry time-of-flight), characterized expression all 14...
Abstract Despite tremendous research efforts, successful targeting of aberrant tumor metabolism in clinical practice has remained elusive. Tumor heterogeneity and plasticity may play a role the failure metabolism-targeting interventions for treating cancer patients. Moreover, compensatory growth-related processes adaptive responses exhibited by heterogeneous subpopulations to metabolic inhibitors are poorly understood. Here, using clinically-relevant patient-derived glioblastoma (GBM) cell...
Abstract Resistance to genotoxic therapies and tumor recurrence are hallmarks of glioblastoma (GBM), an aggressive brain tumor. In this study, we investigated functional drivers post-treatment recurrent GBM through integrative genomic analyses, genome-wide genetic perturbation screens in patient-derived models independent lines validation. Specific dependencies were found consistent across models, accompanied by increased mutational burden differential transcript protein expression compared...
Epidemiological evidence of an association between exposure to chemical carcinogens and increased risk for development glioblastoma (GBM) is limited weak statistical associations in cohorts firefighters, farmers, residents exposed air pollution, soldiers toxic chemicals (e.g., military burn pits, oil-well fire smoke). A history ionizing radiation therapy the head or neck associated with GBM. Ionizing induces point mutations, frameshift double-strand breaks, chromosomal insertions deletions....
Recurrence of solid tumors renders patients vulnerable to advanced, treatment-refractory disease state with mutational and oncogenic landscape distinctive from initial diagnosis. Improving outcomes for recurrent cancers requires a better understanding cell populations that expand the post-therapy, minimal residual (MRD) state. We profile barcoded tumor stem through therapy at initiation, MRD, recurrence in our therapy-adapted, patient-derived xenograft models glioblastoma (GBM). Tumors show...
Brain metastases (BM) are the most common brain neoplasm in adults. Current BM therapies still offer limited efficacy and reduced survival outcomes, emphasizing need for a better understanding of disease. Herein, we analyzed transcriptional profile metastasis initiating cells (BMICs) at two distinct stages metastatic cascade—the “premetastatic” or early stage when they first colonize established macrometastatic stage. RNA sequencing was used to obtain profiles premetastatic...
PTEN mutation occurs in a variety of aggressive cancers and is associated with poor patient outcomes. Recent studies have linked mutational loss to reduced RAD51 expression function, key factor involved the homologous recombination (HR) pathway. However, these remain controversial, as they fail establish definitive causal link that PTEN-dependent, while other not been able recapitulate relationship between RAD51/HR function. Resolution this apparent conundrum essential due...
Glioblastoma (GBM) remains the most common malignant primary brain tumor in adults with a median survival of less than ~15 months. Further understanding and therapeutic development rely on use clinically relevant models GBM. Here, we present our patient-derived vitro vivo that enrich for GBM stem cells (GSCs), subpopulation cell-like properties recapitulate cellular heterogeneity its parental resist conventional therapy seed disease relapse. For complete details execution this protocol,...
Abstract Pediatric medulloblastoma (MB) is the most common solid malignant brain neoplasm, with Group 3 (G3) MB representing aggressive subgroup. MYC amplification an independent poor prognostic factor in G3 MB, however, therapeutic targeting of pathway remains limited and alternative therapies for are urgently needed. Here we show that RNA-binding protein, Musashi-1 (MSI1) essential mediator both -overexpressing mouse models patient-derived xenografts. MSI1 inhibition abrogates tumor...
Advances in chimeric antigen receptor (CAR) T cell therapies have led to the modality dominating translational cancer research; however, a standardized protocol for evaluating such vitro is needed. This details preclinical evaluation of CAR-T glioblastoma (GBM), including target cytotoxicity and proliferation, activation, cytokine release assays. For complete on use execution this protocol, please refer Vora et al. (2020).
Abstract Bacground: Glioblastoma (GBM) is the most common primary brain tumor, accounting for 15% of all central nervous system related tumors. Despite aggressive standard care treatment including chemotherapy, radiotherapy, and maximally safe surgical resection, patient outcomes are abysmal: with 95% patients relapsing a median overall survival 15 months. Thus, this necessitates rapid query personalized therapeutics agents that can potentiate clinical effects currently approved treatments....
Abstract Resistance to genotoxic therapies and tumor recurrence are hallmarks of glioblastoma (GBM), an aggressive brain tumor. Here, we explore the functional drivers post-treatment recurrent GBM. By conducting genome-wide CRISPR-Cas9 screens in patient-derived GBM models, uncover distinct genetic dependencies cells that were absent their patient-matched primary predecessors, accompanied by increased mutational burden differential transcript protein expression. These analyses map a...