A5033179819- Cancer, Hypoxia, and Metabolism
- Glioma Diagnosis and Treatment
- MicroRNA in disease regulation
- Circular RNAs in diseases
- Cancer-related molecular mechanisms research
- ATP Synthase and ATPases Research
- Neurofibromatosis and Schwannoma Cases
- Protein Tyrosine Phosphatases
- Microtubule and mitosis dynamics
- Mitochondrial Function and Pathology
- Melanoma and MAPK Pathways
- Protein Kinase Regulation and GTPase Signaling
- Chromatin Remodeling and Cancer
- Sarcoma Diagnosis and Treatment
- Ubiquitin and proteasome pathways
- Vascular Malformations Diagnosis and Treatment
- Cell Image Analysis Techniques
- Cytokine Signaling Pathways and Interactions
- Neuroblastoma Research and Treatments
- Meningioma and schwannoma management
- Nanoplatforms for cancer theranostics
- Bioinformatics and Genomic Networks
Princess Margaret Cancer Centre
2016-2019
University of Toronto
2016
University Health Network
2014-2016
Center for Neuro-Oncology
2016
Hospital for Sick Children
2014-2015
SickKids Foundation
2014-2015
Abstract Ras is phosphorylated on a conserved tyrosine at position 32 within the switch I region via Src kinase. This phosphorylation inhibits binding of effector Raf while promoting engagement GTPase-activating protein (GAP) and GTP hydrolysis. Here we identify SHP2 as ubiquitously expressed phosphatase that preferentially binds to dephosphorylates increase its association with activate downstream proliferative Ras/ERK/MAPK signalling. In comparison normal astrocytes, activity elevated in...
Abstract Capicua (CIC) is a transcriptional repressor that counteracts activation of genes downstream receptor tyrosine kinase (RTK)/Ras/ERK signaling. It well-established tumorigenesis, especially in glioblastoma (GBM), attributed to hyperactive RTK/Ras/ERK While CIC mutated other tumors, here we show has tumor suppressive function GBM through an alternative mechanism. We find protein levels are negligible due continuous proteasome-mediated degradation, which mediated by the E3 ligase PJA1...
First-line cancer therapies such as alkylating agents and radiation have limited survival benefits for Glioblastoma (GBM) patients. Current research strongly supports the notion that inhibition of aberrant tumor metabolism holds promise a therapeutic strategy when used in combination with chemotherapy. Hexokinase 2 (HK2) has been shown to be key driver altered GBM, presents an attractive target. To date, no study fully assessed value targeting HK2 mechanism sensitize cells standard therapy,...
The RNAse III endonuclease DICER is a key regulator of microRNA (miRNA) biogenesis and frequently decreased in variety malignancies. We characterized the role glioblastoma (GB), specifically demonstrating its effects on ability glioma stem-like cells (GSCs) to form tumors mouse model GB. silencing GSCs reduced their stem cell characteristics, while arising from these were more aggressive, larger volume, displayed higher proliferation index lineage differentiation. resulting tumors, however,...
METB-08. INHIBITION OF HEXOKINASE 2 USING TUMOR GLYCOLYSIS INHIBITORS IDENTIFIED THROUGH A DRUG SCREEN INHIBITS GLIOBLASTOMA GROWTH IN VITRO AND VIVO Gelareh Zadeh1,2, Kenneth Aldape1, Mira Li1, Sameer Agnihotri1, Kelly Burrell1, Alenoush Vartanian1, Amir Alamsahebpour1, and Shahrzad Jalali1; MacFeeters Hamilton Center for Neuro-Oncology, Toronto, ON, Canada; University Health Network, Canada Current research in cancer has demonstrated that normal cells use glucose differently. Normal will...
Rapidly proliferating tumour cells preferentially use aerobic glycolysis over oxidative phosphorylation (OXPHOS) to support growth and survive unfavorable microenvironment conditions. This metabolic reprogramming is referred as the “Warburg effect” offers a novel way target cancer including glioblastoma (GBM), most common malignant brain tumor. Here we demonstrate that Hexokinase 2 (HK2) but not HK1 or HK3 critical mediator of reprograming in GBMs its inhibition potential therapeutic...
INTRODUCTION: Glioblastoma (GBMs) exhibit distinct histopathological features including microvascular hyperplasia and heterogenous hypoxia within the tumor microenvironment. Newly formed vessels are often leaky/dysfunctional with intravascular thrombosis potentially contribute to hypoxic/necrotic foci seen throughout GBMs. By analyzing orthotopic xenograft models of GBM, we have established correlation between blood vessel oxygen diffusion gradient. Additionally, effect anti-angiogenic...
Schwannomas are common benign tumors of the vestibular nerve, or arise from nerves within spinal canal. Although benign, both Spinal schwannoma (SS) and (VS) cause significant morbidities. The current treatment strategies for VS SS include surgery radiation with each option having associated complications side effects. transcriptional landscape remains largely unknown. We interrogated transcriptome by gene-expression array analysis 49 schwannomas seven normal control to identify...
microRNAs have been shown to oncogenic or tumor suppressor function in glioblastoma (GBM). It has postulated that there exists an extensive microRNA-mediated RNA-RNA interaction network GBMs utilizing systems biology approach supporting a competitive endogenous RNA (ce-RNA). MicroRNAs functional relevance the regulation of critical genes and pathways implicated maintenance glioma stem cell (GSC) properties. To address this, we applied biochemical methods establish direct miRNA-mRNA relevant...
Deregulation of microRNA expression is common in a variety malignancies, including glioma. Several studies have demonstrated the role miRNAs regulating glioma stem cell (GSC) properties. In addition, DICER, which regulates processing precursor to mature double-stranded form, down-regulated multiple forms cancer. To determine DICER and miRNA regulation development progression glioblastoma, we investigated link between deregulation GSC characteristics. Our vitro using 7-2 U251 line that...
The RNAse III endonuclease DICER is a key regulator of microRNA (miRNA) biogenesis and frequently down-regulated in variety malignancies. We characterized the role Dicer glioblastoma (GB), specifically demonstrating its effects on ability glioma stem-like cells to form tumors mouse model GB. silencing (GSCs) reduced their stem cell characteristics, while arising from these were more aggressive, larger volume, displayed higher proliferation index lineage differentiation. resulting tumors,...
In the current practice of pathology, identification cell markers and their respective distribution represents an indispensable dialogue for diagnostic, predictive, therapeutic, research purposes. Early immunohistochemical protocols were limited to direct, fluorescent labeled antibodies, yielding quick results but lacking sensitivity. More recently, use indirect techniques –utilization enzyme labels–and various detection systems have continued advance complexity IHC, increasing both its...
Our ongoing work has demonstrated that hexokinase 2 (HK2) but not HK1 or HK3 is a critical mediator of tumour glycolysis and mitochondrial metabolism in Glioblastoma (GB). Furthermore, HK2 highly expressed GB normal brain making it an attractive therapeutic target. current findings now support loss alters tumor vasculature, increases sensitivity to radiation, confers significant survival benefit several xenograft-bearing mice. Using genome wide transcript analysis, we identified attenuates...