A5055181420- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer Cells and Metastasis
- RNA modifications and cancer
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Metabolomics and Mass Spectrometry Studies
- Cell death mechanisms and regulation
- Protein Degradation and Inhibitors
- Phagocytosis and Immune Regulation
- Hedgehog Signaling Pathway Studies
- PI3K/AKT/mTOR signaling in cancer
- CAR-T cell therapy research
- Cancer-related molecular mechanisms research
- Biochemical and Molecular Research
- Cellular Mechanics and Interactions
- Ubiquitin and proteasome pathways
- Chemical Reactions and Isotopes
- Receptor Mechanisms and Signaling
- Estrogen and related hormone effects
- Microtubule and mitosis dynamics
- Immune cells in cancer
- Immune Cell Function and Interaction
McMaster University
2016-2025
University of Toronto
2023-2024
Cellular Research (United States)
2024
University of Waterloo
2014
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 Background Bipolar disorder (BD) has been associated with impaired cellular resilience. Recent studies have shown abnormalities in the unfolded protein response (UPR) BD. The UPR is to endoplasmic reticulum (ER) stress. Mesencephalic astrocyte-derived neurotrophic factor (MANF), a trophic factor, decreases ER stress by modulating UPR. objective of this study investigate MANF-ER pathway BD and major depressive (MDD) compared healthy controls (HC). Methods MANF concentration GRP78...
Breast tumors comprise an infrequent tumor cell population, termed breast initiating cells (BTIC), which sustain growth, seed metastases and resist cytotoxic therapies. Hence therapies are needed to target BTIC provide more durable cancer remissions than currently achieved. We previously reported that serotonergic system antagonists abrogated the activity of mouse resident in mammary a HER2-overexpressing model cancer. Here we report serotonin (5-hydroxytryptamine; 5-HT) biosynthesis...
Histone deacetylase 6 (HDAC6) has been targeted in clinical studies for anticancer effects due to its role oncogenic transformation and metastasis. Through a second-generation structure–activity relationship (SAR) study, the design, biological evaluation of selective HDAC6 inhibitor NN-390 is reported. With nanomolar potency, >200–550-fold selectivity analogous HDAC isoform functional assays, potent intracellular target engagement, robust cellular efficacy cancer cell lines, first...
// Robin M. Hallett 1 , Adele Girgis-Gabardo William D. Gwynne Andrew O. Giacomelli Jennifer N.P. Bisson Jeremy E. Jensen Anna Dvorkin-Gheva 2 John A. Hassell 1, 2, 3 Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada Pathology Molecular Medicine, Biology, ON, Correspondence to: Hassell, email: hassell@mcmaster.ca Keywords: breast cancer, tumor-initiating cells, serotonin antagonists, anticancer stem cell drugs Received: April 01,...
Breast tumor growth and recurrence are driven by an infrequent population of breast tumor-initiating cells (BTIC). We others have reported that the frequency BTIC is orders magnitude higher when propagated in vitro as clonal spheres, termed tumorspheres, comparison to adherent cells. exploited latter screen > 35,000 small molecules identify agents capable targeting BTIC. unexpectedly discovered selective antagonists serotonin signaling were among hit compounds. To better understand...
Abstract Background Breast tumor initiating cells (BTIC) are stem-like that initiate and sustain growth, drive disease recurrence. Identifying therapies targeting BTIC has been hindered due primarily to their scarcity in tumors. We previously reported frequency ranges between 15% 50% multiple mammary tumors of 3 different transgenic mouse models breast cancer this is maintained cell populations cultured serum-free, chemically defined media as non-adherent tumorspheres. The latter enabled...
Gene expression profiling of medulloblastoma cells undergoing therapy identifies BPIFB4 as a novel target for recurrent disease.
Abstract Previous research has suggested that thyroid hormone receptor alpha 1 (THRα1), a responsive splice variant, may play role in breast cancer progression. Whether THRα1 can be exploited for anti-cancer therapy is unknown. The antiproliferative and antitumor effects of dronedarone, an FDA-approved anti-arrhythmic drug which been shown to antagonize THRα1, was evaluated cell lines vitro vivo . variant the entire receptor, THRα, were also independently targeted using siRNA determine...
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...
Medulloblastoma (MB) is the most common type of malignant pediatric brain cancer. The current standard care (SOC) involves maximal safe resection and chemoradiotherapy in individuals older than 3 years, often leading to devastating neurocognitive developmental deficits. Out four distinct molecular subgroups, Group 4 have poorest patient outcomes due aggressive nature tumor propensity metastasize recur post therapy. toxicity SOC lack response specific subtypes underscores urgent need for...
Most nucleus-encoded chloroplast proteins rely on an N-terminal transit peptide (TP) as a post-translational sorting signal for directing them to the organelle. Although Toc159 is known be receptor specific preprotein TPs at surface, mechanism its own targeting and integration into outer membrane not completely understood. In previous study, we identified novel TP-like C-terminus (CT) of homolog from single-cell C4 species, Bienertia sinuspersici. current have extended our understanding...
Liquid chromatography-mass spectrometry (LC-MS)-based metabolomics and lipidomics have recently been used to show that MYC-amplified group 3 medulloblastoma tumors are driven by metabolic reprogramming. Here, we present a protocol extract metabolites lipids from human brain tumor-initiating cells normal neural stem cells. We describe untargeted LC-MS methods can be achieve extensive coverage of the polar metabolome lipidome. Finally, detail strategies for metabolite identification data...
Abstract Patients with brain metastases (BM) face a 90% mortality rate within one year of diagnosis and the current standard care is mainly palliative. Targeting BM-initiating cells (BMIC) feasible strategy to treat BM, but druggable targets are still very limited. Here, we applied Connectivity Map analysis lung-, breast-, melanoma- pre-metastatic BMIC gene expression signatures identified inosine monophosphate dehydrogenase (IMPDH), rate-limiting enzyme in de novo GTP synthesis pathway, as...
Resistance to chemotherapy remains a major hurdle the cure of Acute Myeloid Leukemia (AML) patients. Recent studies indicate minority malignant cells, termed drug-tolerant persisters (DTPs), stochastically upregulate stress pathways evade cell death upon acute exposure without acquiring new genetic mutations. This chemoresistant state is transient and cells return baseline after removal chemotherapy. Yet, mechanisms employed by DTPs resist are not well understood it largely unknown whether...
Abstract Metastasis, the spread of cancer cells from one part body to another, is a leading cause death among patients. Three particularly dangerous forms metastases are lung, skin, and breast cancers brain. On average survival time all brain metastasis (BM) patients around 4 months, which accompanied by failing undefined standard care. We have strived bridge gap between novel safe therapeutics discovering targeting metabolic vulnerabilities in metastases. Here, we conducted comparative...
Pediatric central nervous system (CNS) tumors are the most common solid diagnosed in children and leading cause of pediatric cancer-related death. Those who do survive faced with long-term adverse effects current standard care treatments chemotherapy, radiation, surgery. There is a pressing need for novel therapeutic strategies to treat CNS more effectively while reducing toxicity - one these modalities chimeric antigen receptor (CAR) T-cell therapy. Currently approved use several...
Abstract INTRO: Patients with brain metastases (BM) face a 90% mortality rate within one year of their diagnosis and they lack targeted therapeutic options, particularly preventative or interceptional ones. METHODS: The Singh lab has generated large in-house biobank patient-derived BM cell lines that are established from primary lung breast cancers melanoma. We use these to generate murine orthotopic xenograft models interrogate the biological processes lead BM. These have successfully...