A5022430073- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Cancer Research and Treatments
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- Immune cells in cancer
- Neurofibromatosis and Schwannoma Cases
- Cancer-related molecular mechanisms research
- 3D Printing in Biomedical Research
- Radiomics and Machine Learning in Medical Imaging
- ATP Synthase and ATPases Research
- Dermatologic Treatments and Research
- Cancer Cells and Metastasis
- Chromatin Remodeling and Cancer
- Tissue Engineering and Regenerative Medicine
- Hair Growth and Disorders
- Circular RNAs in diseases
- Protein Kinase Regulation and GTPase Signaling
- Biomedical Ethics and Regulation
- Electrospun Nanofibers in Biomedical Applications
- Food Quality and Safety Studies
- Protein Degradation and Inhibitors
University Health Network
2015-2024
Princess Margaret Cancer Centre
2016-2023
University of Toronto
2017-2023
Lunenfeld-Tanenbaum Research Institute
2013-2017
Mount Sinai Hospital
2013-2017
QIMR Berghofer Medical Research Institute
2015
Chungnam National University
2011
Abstract Reprogramming of somatic cells to induced pluripotent stem involves a dynamic rearrangement the epigenetic landscape. To characterize this epigenomic roadmap, we have performed MethylC-seq, ChIP-seq (H3K4/K27/K36me3) and RNA-Seq on samples taken at several time points during murine secondary reprogramming as part Project Grandiose. We find that DNA methylation gain occurs gradually, while loss is achieved only ESC-like state. Binding sites activated factors exhibit focal...
Abstract Reprogramming is a dynamic process that can result in multiple pluripotent cell types emerging from divergent paths. Cell surface protein expression particularly desirable tool to categorize reprogramming and pluripotency as it enables robust quantification enrichment of live cells. Here we use proteomics interrogate mouse dynamics discover CD24 marker tracks the emergence reprogramming-responsive cells, while enabling analysis transgene-dependent (F-class) -independent...
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...
Abstract Purpose: Hexokinase II (HK2) protein expression is elevated in glioblastoma (GBM), and we have shown that HK2 could serve as an effective therapeutic target for GBM. Here, interrogated compounds effectively restrict tumor growth cell lines, patient-derived glioma stem cells (GSCs), mouse models of Experimental Design: We performed a screen using set 15 drugs were predicted to inhibit the HK2-associated gene signature. next determined EC50 by treating lines GSCs. Selected showing...
Abstract One of the most prominent features glioblastoma (GBM) is hyper-vascularization. Bone marrow-derived macrophages are actively recruited to tumor and referred as glioma-associated (GAMs) which thought provide a critical role in neo-vascularization. However, mechanisms by GAMs regulate endothelial cells (ECs) process vascularization response anti-angiogenic therapy (AATx) not well-understood. Here we show that GBM secrete IL-8 CCL2 stimulate produce TNFα. Subsequently, TNFα induces...
The development of strategies for tissue regeneration and bio-artificial organ is based on our understanding embryogenesis. Differentiation protocols attempt to recapitulate the signaling modalities gastrulation organogenesis, coupled with cell selection regimens isolate cells choice. This strategy impeded by lack optimal in vitro culture systems since traditional do not allow three-dimensional interaction between extracellular matrix. While artificial scaffolds are available, using natural...
<b>Background:</b> Hair loss is seen as an irreversible process. Most research concentrates on how to elongate the anagen, reduce negative factors of obstructing hair growth and improve number size. <b>Aim:</b> In our experiment, we tried prove that cow placenta extract can promote by elongating shaft increasing follicle number. <b>Materials Methods:</b> Cow (CPE), water minoxidil applied separately back depilated B57CL/6 mice for case, positive control respectively. We checked proliferation...
Human hematopoietic stem cell engraftment has been studied extensively using xenograft transplant models with immunocompromised mice. It is standard practice to incorporate mouse models, such as the limiting dilution assay, accurately assess number of repopulating cells in bone marrow or umbilical cord blood collections confirm long-term ability cultured cells. In a previous study NOD/SCID model human we observed that all had MHC class I protein on their surface, suggesting this mechanism...
Abstract Glioblastoma (GBM) is a fatal brain cancer in adults with ineffective treatment methods. Cell adhesion molecules (CAMs) are proteins that expressed on the surface of cells and enable them to interact one another surrounding microenvironment. Intracellular molecule 1 (ICAM-1) cell by various types. Preliminary data showed ICAM-1 associated poorer overall progression free survival patients expression levels increase recurrent tumors. TAMs enhance GBM tumor growth. The aim this study...
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,...
Abstract Glioblastoma (GBM) remains a universal fatal disease and improving survival challenge. One of the most prominent features GBM is hyper-vascularization, characterized by abnormally dilated, distorted, leaky vessels. Bone marrow (BM)-derived macrophages are recognized to be an important host cell population that actively recruited tumor referred as glioma-associated (GAMs). GAMs found associate closely with blood vessels, thought provide critical role in neo-vascularization. However,...
Abstract Gliobastoma (GBM) is a highly aggressive solid tumor of the brain, characterized by hypoxic microevironment (TME) leading to histopathological features necrosis, microvascular proliferation and deregulated hypervascularization. The heterogeneous nature GBM results in gradient intra-tumoral hypoxia that causes molecular changes specific cell populations within bulk tumor. Our study first clinical utilize exogenous oxygen-independent marker pimonidazole (PIMO) identify TME using...
Abstract A new mouse model for the classical subtype of human glioblastoma (GBM) has been bred using Cre-mediated EGFRvIII overexpression and homozygous p19-ARF deletion, homolog p14ARF/CDKN2A, in GFAP expressing cells. Transgenic mice develop intraparenchymal and/or leptomeningeal brain lesions with some spinal cord invasion as early 1 month old 95% die by 6 months due to hydrocephalus paralysis. Mice high grade tumors have worse survival similar features GBM such necrosis, levels mitosis...
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...
Schwannomas are common cranial and spinal nerve tumors that can cause significant debilitating morbidities. To date, clinical trials for schwannomas have yielded mixed to no benefits this may be in part due a lack of fully understanding the somatic alterations occur schwannoma. We performed an integrative multiplatform analysis determine genomic landscape sporadic schwannomas. Exome sequence with validation by targeted DNA-sequencing 125 samples uncovered, addition expected NF2 disruption,...
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...
GBM tumors are recognized as being heterogeneous in nature, consisting of many different cell types and states. This presents a major hurdle during the treatment radiation chemotherapeutic agents preferentially target proliferative cells. Notably, quiescent slowly-dividing cancer stem cells thought to provide reserve that drive relapse following treatment, making them more malignant than their rapidly dividing counter-parts. To determine whether slow common feature within patient GBMs we...