A5089038043- Neurogenesis and neuroplasticity mechanisms
- Glioma Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Neuroscience and Neuropharmacology Research
- Amino Acid Enzymes and Metabolism
- MicroRNA in disease regulation
- Cancer Cells and Metastasis
- Nerve injury and regeneration
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer Genomics and Diagnostics
- Ion channel regulation and function
- Pluripotent Stem Cells Research
- Cytokine Signaling Pathways and Interactions
- Metabolism and Genetic Disorders
- Chemical Reactions and Isotopes
- Axon Guidance and Neuronal Signaling
- Microtubule and mitosis dynamics
- Neuroendocrine regulation and behavior
- Single-cell and spatial transcriptomics
- Neuropeptides and Animal Physiology
- Autophagy in Disease and Therapy
- Cancer Mechanisms and Therapy
- Cancer Research and Treatments
- Olfactory and Sensory Function Studies
Ontario Brain Institute
2009-2025
University of Calgary
2015-2025
Cancer Institute (WIA)
2019-2024
Allen Institute for Brain Science
2007-2024
University of British Columbia
2009-2024
Nationwide Children's Hospital
2023
University of Illinois Urbana-Champaign
2020
Princeton University
1969-2020
University of Maryland, College Park
2020
Rutgers, The State University of New Jersey
2020
Neurogenesis in the mammalian central nervous system is believed to end period just after birth; mouse striatum no new neurons are produced first few days birth. In this study, cells isolated from of adult brain were induced proliferate vitro by epidermal growth factor. The proliferating initially expressed nestin, an intermediate filament found neuroepithelial stem cells, and subsequently developed morphology antigenic properties astrocytes. Newly generated with neuronal immunoreactive for...
The mitogenic actions of epidermal growth factor (EGF) were examined in low-density, dissociated cultures embryonic day 14 mouse striatal primordia, under serum-free defined conditions. EGF induced the proliferation single progenitor cells that began to divide between 5 and 7 d vitro, after 13 vitro had formed a cluster undifferentiated expressed nestin, an intermediate filament present neuroepithelial stem cells. In continued presence EGF, migrated from proliferating core differentiated...
Neural stem cells in the lateral ventricles of adult mouse CNS participate repopulation forebrain structures vivo and are amenable to vitro expansion by epidermal growth factor (EGF). There have been no reports more caudal brain regions or spinal cord mammals. In this study we found that although ineffective alone, EGF basic fibroblast (bFGF) cooperated induce proliferation, self-renewal, neural isolated from thoracic cord. The proliferating cells, both primary culture secondary expanded...
The lateral ventricle subependyma in the adult mammalian forebrain contains both neural stem and progenitor cells. This study describes situ modulation of these subependymal precursor populations after intraventricular administration exogenous growth factors. In vivo infusion epidermal factor (EGF) into mouse for 6 consecutive days resulted a dramatic increase proliferation total number cells induced their migration away from walls adjacent parenchyma. Immediately EGF infusion,...
Neurogenesis occurs in the olfactory system of adult brain throughout life, both invertebrates and vertebrates, but its physiological regulation is not understood. We show that production neuronal progenitors stimulated forebrain subventricular zone female mice during pregnancy this effect mediated by hormone prolactin. The then migrate to produce new interneurons, a process likely be important for maternal behavior, because discrimination critical recognition rearing offspring. even females...
Recent studies have shown that neurogenesis is enhanced after hypoxia and erythropoietin (EPO), an inducible cytokine, produced in the brain as part of intrinsic response. Thus, we asked whether EPO might regulate by forebrain neural stem cells (NSCs). We found receptors are expressed embryonic germinal zone during well adult subventricular zone, which continues to generate neurons throughout adulthood. Cultured NSCs exposed a modest two- threefold more neurons, was associated with elevation...
Previous studies demonstrating olfactory interneuron involvement in discrimination and decreased proliferation the forebrain subventricular zone with age led us to ask whether neurogenesis and, consequently, were impaired aged mice. Pulse labeling showed that mice (24 months of age) had fewer new interneurons bulb than did young adult (2 However, more total their younger counterparts. Aged exhibited no differences from ability discriminate between two discrete odors but significantly poorer...
Oligodendroglioma is characterized by unique clinical, pathological, and genetic features. Recurrent losses of chromosomes 1p 19q are strongly associated with this brain cancer but knowledge the identity function genes affected these alterations limited. We performed exome sequencing on a discovery set 16 oligodendrogliomas 1p/19q co-deletion to identify new molecular features at base-pair resolution. As anticipated, there was high rate IDH mutations: all cases had mutations in either IDH1...
Glioblastoma therapies have remained elusive due to limitations in understanding mechanisms of growth and survival the tumorigenic population. Using CRISPR-Cas9 approaches patient-derived GBM stem cells (GSCs) interrogate function coding genome, we identify actionable pathways responsible for growth, which reveal gene-essential circuitry stemness proliferation. In particular, characterize members SOX transcription factor family, SOCS3, USP8, DOT1L, protein ufmylation as important GSC growth....
Glioblastoma is one of the most lethal cancers in humans, and with existing therapy, survival remains at 14.6 months. Current barriers to successful treatment include their infiltrative behavior, extensive tumor heterogeneity, presence a stem-like population cells, termed brain tumor-initiating cells (BTIC) that confer resistance conventional therapies.To develop therapeutic strategies target BTICs, we focused on repurposing approach explored already-marketed (clinically approved) drugs for...
Abstract Glioblastoma (GBM) is a deadly cancer in which stem cells (CSCs) sustain tumor growth and contribute to therapeutic resistance. Protein arginine methyltransferase 5 (PRMT5) has recently emerged as promising target GBM. Using two orthogonal-acting inhibitors of PRMT5 (GSK591 or LLY-283), we show that pharmacological inhibition suppresses the cohort 46 patient-derived GBM cell cultures, with proneural subtype showing greater sensitivity. We causes widespread disruption splicing across...
We have previously reported the isolation of an EGF-responsive precursor from embryonic and adult mouse striatum. This exhibits self renewal ability to produce a sphere undifferentiated cells which can be induced differentiate into neurons glia. RT-PCR analysis these spheres revealed expression mRNA for trkB neurotrophin receptor, both with without catalytic domain, little or no trkA trkC. examined actions BDNF on fate EGF-generated neural precursors. Ten days after one-time exposure BDNF,...
Hes1 is one of the basic helix-loop-helix transcription factors that regulate mammalian CNS development, and its loss- gain-of-function phenotypes indicate it negatively regulates neuronal differentiation. Here we report Hes1(-/-) mice expressed both early (TuJ1 Hu) late (MAP2 Neurofilament) markers prematurely, there were approximately twice normal number neurons in brain during neural development. However, immunochemical analyses sections dissociated cells using progenitor markers,...
The cytokines that signal through the common receptor subunit gp130, including ciliary neurotrophic factor (CNTF), interleukin-6, leukemia inhibitory (LIF) and oncostatin M, have pleiotropic functions in CNS development. Given restricted expression domain of CNTF α (CNTFR) developing forebrain germinal zone adult periventricular area, we examined putative role CNTFR/LIFR/gp130-mediated signaling regulating neural stem cell fate <i>in vivo</i> vitro</i>. Analysis of<i>LIFR</i>-deficient mice...
Recent studies suggest that proliferation in the adult forebrain subventricular zone increases response to a stroke and intraventricular infusions of growth factors enhance this response. The potential for factor regenerate damaged motor cortex promote recovery function after has not been examined. Here, we report epidermal erythropoietin together, but individually, substantial regeneration cerebral reverse impairments spontaneous skilled tasks, rat model stroke. Cortical functional occurred...
Neural stem cells (NSCs), when stimulated with epidermal growth factor (EGF) or fibroblast factor-2 (FGF-2), have the capacity to renew, expand, and produce precursors for neurons, astrocytes, oligodendrocytes. We postulated that early appearance of insulin-like (IGF-I) receptors during mouse striatum development implies a role in NSC regulation. Thus, we tested vitro action IGF-I on proliferation striatal NSCs. In absence IGF-I, neither EGF nor FGF-2 was able induce E14 cells. However,...
Myelination, the process in which oligodendrocytes coat CNS axons with a myelin sheath, represents an important but poorly understood form of neural plasticity that may be sexually dimorphic adult CNS. Remission multiple sclerosis during pregnancy led us to hypothesize remyelination is enhanced maternal brain. Here we report increase generation myelin-forming and number myelinated murine Remarkably, pregnant mice have ability remyelinate white matter lesions. The hormone prolactin regulates...