A5063733303- Glioma Diagnosis and Treatment
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Cancer Cells and Metastasis
- Axon Guidance and Neuronal Signaling
- Single-cell and spatial transcriptomics
- Protein Degradation and Inhibitors
- Neuroinflammation and Neurodegeneration Mechanisms
- Angiogenesis and VEGF in Cancer
- Reproductive System and Pregnancy
- Cancer Research and Treatments
- Nanoplatforms for cancer theranostics
- Ubiquitin and proteasome pathways
- Chromatin Remodeling and Cancer
- Polyomavirus and related diseases
- Phagocytosis and Immune Regulation
- Cancer Immunotherapy and Biomarkers
- Cell Image Analysis Techniques
- interferon and immune responses
- Cancer Genomics and Diagnostics
- Sarcoma Diagnosis and Treatment
- Melanoma and MAPK Pathways
- 3D Printing in Biomedical Research
- Monoclonal and Polyclonal Antibodies Research
McMaster University
2018-2024
University of Basel
2022-2024
Discovery Centre
2022-2024
University Hospital of Basel
2022-2023
University of Manitoba
2015-2019
Glioblastoma (GBM) is the most aggressive form of primary brain tumor, for which effective therapies are urgently needed. Cancer cells capable evading clearance by phagocytes such as microglia- and monocyte-derived through engaging tolerogenic programs. Here, we found that high expression sialic acid–binding immunoglobulin-like lectin 9 (Siglec-9) correlates with reduced survival in patients GBM. Using cell-specific knockouts Siglec-E, murine functional homolog Siglec-9, together single-cell...
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.
Abstract Medulloblastoma (MB) is defined by four molecular subgroups (Wnt, Shh, Group 3, 4) with Wnt MB having the most favorable prognosis. Since prior reports have illustrated antitumorigenic role of activation in Shh MB, we aimed to assess effects activated canonical signaling 3 and 4 MBs. By using primary patient-derived brain tumor-initiating cell (BTIC) lines, characterize differences capacity Wnt, MB. With single RNA-seq technology, demonstrate presence rare Wnt-active cells non-Wnt...
Abstract Neutrophil migration is an essential step in leukocyte trafficking during inflammatory responses. Semaphorins, originally discovered as axon guidance cues neural development, have been shown to regulate cell beyond the nervous system. However, potential contribution of semaphorins regulation neutrophil not well understood. This study examines possible role a secreted chemorepellent, Semaphorin 3E (Sema3E), migration. In this study, we demonstrated that human neutrophils...
Abstract The extensive heterogeneity both between and within the medulloblastoma subgroups underscores a critical need for variant-specific biomarkers therapeutic strategies. We previously identified role CD271/p75 neurotrophin receptor (p75NTR) in regulating stem/progenitor cells SHH subgroup. Here, we demonstrate utility of CD271 as novel diagnostic prognostic marker using IHC analysis transcriptome data across 763 primary tumors. RNA sequencing CD271+ CD271− revealed molecularly distinct,...
Airway smooth muscle (ASM) hyperplasia is a key feature of airway remodeling in development lung diseases such as asthma. Anomalous proliferation ASM cells directly contributes to hyperplasia. However, the molecular mechanisms controlling cell are not completely understood. Semaphorins versatile regulators various cellular processes including growth and proliferation. The role semaphorins has remained be addressed. Here, we report that semaphorin 3A (Sema3A) receptor, neuropilin 1 (Nrp1),...
// Lisa Liang 1,* , Christopher Aiken Robyn McClelland 1 Ludivine Coudière Morrison Nazanin Tatari 2 Marc Remke 3 Vijay Ramaswamy Magimairajan Issaivanan 4 Timothy Ryken 5 R. Del Bigio 6 Michael D. Taylor and Tamra E. Werbowetski-Ogilvie Regenerative Medicine Program, Department of Biochemistry Medical Genetics, University Manitoba, Winnipeg, Canada Immunology, Arthur Sonia Labatt Brain Tumour Research Centre Program in Developmental Stem Cell Biology, The Hospital for Sick Children,...
Medulloblastoma ( MB ) is the most common malignant primary pediatric brain cancer. Among aggressive subtypes, Group 3 and 4 originate from stem/progenitor cells, frequently metastasize, often display worst prognosis, yet we know least about molecular mechanisms driving their progression. Here, show that transcription factor orthodenticle homeobox 2 OTX 2) promotes self‐renewal while inhibiting differentiation in vitro increases tumor initiation cells vivo . To determine how contributes to...
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...
Gene expression profiling of medulloblastoma cells undergoing therapy identifies BPIFB4 as a novel target for recurrent disease.
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...
A significant challenge for chimeric antigen receptor (CAR) T cell therapy against glioblastoma (GBM) is its immunosuppressive microenvironment, which densely populated by protumoral glioma-associated microglia and macrophages (GAMs). Myeloid immune checkpoint targeting the CD47-signal regulatory protein alpha (SIRPα) axis induces GAM phagocytic function, but CD47 blockade monotherapy associated with toxicity low bioavailability in solid tumors. In this work, we engineer a CAR epidermal...
Glioblastomas (GBM), the most common malignant primary adult brain tumors, are uniformly lethal and in need of improved therapeutic modalities. GBM contain extensive regions hypoxia enriched therapy resistant tumor-initiating cells (BTICs). Carbonic anhydrase 9 (CA9) is a hypoxia-induced cell surface enzyme that plays an important role maintenance stem survival resistance. Here we demonstrate CA9 highly expressed patient-derived BTICs. + BTICs showed increased self-renewal proliferative...
Glioblastoma (GBM) is the most common malignant adult brain tumor that resistant to standard care therapy. Advances in chimeric antigen receptor (CAR) T cell therapies have spurred renewed interest developing CAR target chemoradiotherapy-resistant tumor-initiating cells. This protocol shows how isolate peripheral blood mononuclear cells from healthy donors and generate for antigens of interest, intracranially inject into a patient-derived xenograft mouse model GBM. For complete details on...
Abstract A major challenge for chimeric antigen receptor (CAR) T cell therapy against glioblastoma (GBM) is the immunosuppressive microenvironment (iTME), which densely populated by protumoral glioma-associated microglia and macrophages (GAMs). Blockade of CD47, a “don’t-eat-me” signal overexpressed GBM cells, disrupts CD47-SIRPα axis, regulates phagocytic function GAMs. However, systemic anti-CD47 monotherapy has been ineffective human solid tumors to date. Here, we combined local CAR with...
<title>Abstract</title> Cancer intrinsic immune evasion mechanisms and pleiotropy represent a barrier to effective translation of cancer immunotherapy. This is acutely apparent for certain highly fatal cancers such as high-grade gliomas glioblastomas. In this study, we use functional genetic screens, single-cell transcriptomics machine-learning approaches deeply characterize murine syngeneic glioma models <italic>in vitro</italic> vivo</italic>, compare-and-contrast their value preclinical...
Abstract BACKGROUND Glioblastoma is the most common malignant primary brain tumor in adults with a poor survival and an unmet need for more effective therapies. Macroscopically, as observed through MR imaging microscopy, these tumors are characterized by distinct regions: contrast-enhancing core high cancer cell density infiltration zone that appears T2/FLAIR hyperintense without uptake of contrast agent consists infiltrating cells well non-malignant microenvironment. Previous genomic...