• By training, I am an academic neurosurgeon conducting both brain tumor translational research and clinical brain tumor surgery. As a physician, I surgically treat patients with brain tumors. As a scientist, I focus on the molecular characterization of brain cancer heterogeneity and plasticity and translate that knowledge to cancer therapeutics. My research is highlighted with the discovery of brain cancer stem cells, published in PNAS in 2003, and the discovery of glioblastoma subtype-specific cancer stem cells, published in PNAS, Cancer Cell in 2013, and Cancer Cell in 2016. Since 2016, I have published more than 105 peer-reviewed research and review articles. I currently hold 7 NIH grants as a PI (6 R01s and 1 R21). All of these projects aim to study various molecular mechanisms that drive brain cancer aggressiveness, heterogeneity, therapy resistance and development.

    In October 2015, I was recruited to the UAB Department of Neurosurgery. Since I joined UAB, I have thoroughly integrated myself into the UAB brain tumor program and have taken on leadership roles. For example, I serve as a co-Leader in the Neuro-Oncology Program in UAB Comprehensive Cancer Center. Under this mechanism, I aim to be among the national and international leaders in therapeutic development for brain cancers. My research projects are extensively supported by many collaborations and I have assembled neuro-oncology scientists and physicians covering various and broad expertise into my team. We share the mission to identify novel and effective therapies for malignant brain tumors as a result of our collaborative work.

    My long-term goal is to make visible impact on prognosis of cancer patients by developing innovative and effective therapies. I continue to devote myself towards improving the outcomes of patients by developing effective therapies for this devastating disease in collaboration with my collaborators including basic scientists, oncologists, pathologists, and neurosurgeons.

    Brain tumors
    Functional Mapping
    Intraoperative MRI
    Fluorescence-guided brain surgery
    Minimally-invasive surgery
    Microvascular decompression

    Molecular characterization of brain tumor stem cells
    Therapy development for brain tumors
    Phase I/II Clinical Trial for malignant brain tumors
    Molecular mechanism of therapy resistance of brain tumors
    Genetic mechanism for cell fate decisions in neural stem cells
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2020 Identification of ALDH1A3 as a Viable Therapeutic Target in Breast Cancer Metastasis-Initiating Cells. 2020
    2020 Enhanced fatty acid oxidation provides glioblastoma cells metabolic plasticity to accommodate to its dynamic nutrient microenvironment 2020
    2020 ICOSLG-mediated regulatory T-cell expansion and IL-10 production promote progression of glioblastoma 2020
    2020 ΔNp73/ETS2 complex drives glioblastoma pathogenesis- targeting downstream mediators by rebastinib prolongs survival in preclinical models of glioblastoma 2020
    2020 An update on neurofibromatosis type 1-associated gliomas 2020
    2020 Laminin is the ECM niche for trophoblast stem cells 2020
    2019 Author Correction: Sustained NF-κB-STAT3 signaling promotes resistance to Smac mimetics in Glioma stem-like cells but creates a vulnerability to EZH2 inhibition (Cell Death Discovery, (2019), 5, 1, (72), 10.1038/s41420-019-0155-9) 2019
    2019 Sustained NF-κB-STAT3 signaling promotes resistance to Smac mimetics in Glioma stem-like cells but creates a vulnerability to EZH2 inhibition 2019
    2019 Intratumoral spatial heterogeneity of BTK kinomic activity dictates distinct therapeutic response within a single glioblastoma tumor. 2019
    2019 SRSF3-regulated RNA alternative splicing promotes glioblastoma tumorigenicity by affecting multiple cellular processes 2019
    2019 Current Approaches and Challenges in the Molecular Therapeutic Targeting of Glioblastoma 2019
    2019 Molecular and cellular intratumoral heterogeneity in primary glioblastoma: clinical and translational implications. 2019
    2019 IMP dehydrogenase-2 drives aberrant nucleolar activity and promotes tumorigenesis in glioblastoma 2019
    2019 TOP2B Enzymatic Activity on Promoters and Introns Modulates Multiple Oncogenes in Human Gliomas 2019
    2019 MIR93 (microRNA -93) regulates tumorigenicity and therapy response of glioblastoma by targeting autophagy 2019
    2019 Statins affect human glioblastoma and other cancers through TGF-β inhibition 2019
    2019 Phenotypic Plasticity of Invasive Edge Glioma Stem-like Cells in Response to Ionizing Radiation 2019
    2019 Integrative cross-platform analyses identify enhanced heterotrophy as a metabolic hallmark in glioblastoma 2019
    2018 5-Aminolevulinic acid-mediated photodynamic therapy can target human glioma stem-like cells refractory to antineoplastic agents 2018
    2018 A PDGFRα-driven mouse model of glioblastoma reveals a stathmin1-mediated mechanism of sensitivity to vinblastine 2018
    2018 miRNA-mediated TUSC3 deficiency enhances UPR and ERAD to promote metastatic potential of NSCLC 2018
    2018 Correction to: AMP kinase promotes glioblastoma bioenergetics and tumour growth (Nature Cell Biology, (2018), 20, 7, (823-835), 10.1038/s41556-018-0126-z) 2018
    2018 Erratum to: AMP kinase promotes glioblastoma bioenergetics and tumour growth (Nature Cell Biology, (2018), 20, 7, (823-835), 10.1038/s41556-018-0126-z) 2018
    2018 A small molecule regulator of tissue transglutaminase conformation inhibits the malignant phenotype of cancer cells 2018
    2018 Combined c-Met/Trk inhibition overcomes resistance to CDK4/6 inhibitors in Glioblastoma 2018
    2018 Apoptotic Cell-Derived Extracellular Vesicles Promote Malignancy of Glioblastoma Via Intercellular Transfer of Splicing Factors 2018
    2018 AMP kinase promotes glioblastoma bioenergetics and tumour growth 2018
    2018 Activation of the receptor tyrosine kinase AXL regulates the immune microenvironment in glioblastoma 2018
    2018 Toxicity and efficacy of a novel gadd34-expressing oncolytic hsv-1 for the treatment of experimental glioblastoma 2018
    2018 Genome-wide methylomic and transcriptomic analyses identify subtype-specific epigenetic signatures commonly dysregulated in glioma stem cells and glioblastoma 2018
    2018 Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles 2018
    2018 Divergent evolution of temozolomide resistance in glioblastoma stem cells is reflected in extracellular vesicles and coupled with radiosensitization 2018
    2018 Targeting the mesenchymal subtype in glioblastoma and other cancers via inhibition of diacylglycerol kinase alpha 2018
    2018 Differential response of glioma stem cells to arsenic trioxide therapy is regulated by MNK1 and mRNA translation 2018
    2018 Molecular subtypes and differentiation programmes of glioma stem cells as determinants of extracellular vesicle profiles and endothelial cell-stimulating activities 2018
    2017 Inhibition of Farnesyltransferase Potentiates NOTCH-Targeted Therapy against Glioblastoma Stem Cells 2017
    2017 MST4 Phosphorylation of ATG4B Regulates Autophagic Activity, Tumorigenicity, and Radioresistance in Glioblastoma 2017
    2017 SHP2 regulates proliferation and tumorigenicity of glioma stem cells 2017
    2017 Targeting glioma stem cells in vivo by a G-quadruplex-stabilizing synthetic macrocyclic hexaoxazole 2017
    2017 GPR56/ADGRG1 Inhibits Mesenchymal Differentiation and Radioresistance in Glioblastoma 2017
    2017 Combined CDK4/6 and mTOR inhibition is synergistic against glioblastoma via multiple mechanisms 2017
    2017 Transglutaminase 2 inhibition reverses mesenchymal transdifferentiation of glioma stem cells by regulating C/EBPβ signaling 2017
    2017 CDK4/6 inhibition is more active against the glioblastoma proneural subtype. 2017
    2017 Targeting NEK2 attenuates glioblastoma growth and radioresistance by destabilizing histone methyltransferase EZH2 2017
    2017 The Fc Domain of Immunoglobulin Is Sufficient to Bridge NK Cells with Virally Infected Cells 2017
    2017 MicroRNA Signatures and Molecular Subtypes of Glioblastoma: The Role of Extracellular Transfer 2017
    2017 MicroRNA-Mediated Dynamic Bidirectional Shift between the Subclasses of Glioblastoma Stem-like Cells 2017
    2017 Erratum: Feedback Loop Regulation of SCAP/SREBP-1 by miR-29 Modulates EGFR Signaling-Driven Glioblastoma Growth (Cell Reports (2016) 16(6) (1527–1535)(S2211124716309032)(10.1016/j.celrep.2016.07.017)) 2017
    2017 CDK4/6 inhibition is more active against the glioblastoma proneural subtype 2017
    2017 Dissecting inherent intratumor heterogeneity in patient-derived glioblastoma culture models 2017
    2017 The stem cell/cancer stem cell marker ALDH1A3 regulates the expression of the survival factor tissue transglutaminase, in mesenchymal glioma stem cells 2017
    2016 FOXD1-ALDH1A3 signaling is a determinant for the self-renewal and tumorigenicity of mesenchymal glioma stem cells 2016
    2016 Inhibition of SOAT1 suppresses glioblastoma growth via blocking SREBP-1-mediated lipogenesis 2016
    2016 SHP-2-upregulated ZEB1 is important for PDGFRα-driven glioma epithelial-mesenchymal transition and invasion in mice and humans 2016
    2016 A regulatory circuit of miR-125b/miR-20b and Wnt signalling controls glioblastoma phenotypes through FZD6-modulated pathways 2016
    2016 MNK inhibition disrupts mesenchymal glioma stem cells and prolongs survival in a mouse model of glioblastoma 2016
    2016 On-Chip Clonal Analysis of Glioma-Stem-Cell Motility and Therapy Resistance 2016
    2016 Feedback Loop Regulation of SCAP/SREBP-1 by miR-29 Modulates EGFR Signaling-Driven Glioblastoma Growth 2016
    2016 Cancer Stem Cell-Secreted Macrophage Migration Inhibitory Factor Stimulates Myeloid Derived Suppressor Cell Function and Facilitates Glioblastoma Immune Evasion 2016
    2016 The Long Non-coding RNA HIF1A-AS2 Facilitates the Maintenance of Mesenchymal Glioblastoma Stem-like Cells in Hypoxic Niches 2016
    2016 Targeting of glioblastoma cell lines and glioma stem cells by combined PIM kinase and PI3K-p110a inhibition 2016
    2016 Extracellular vesicles from high-grade glioma exchange diverse pro-oncogenic signals that maintain intratumoral heterogeneity 2016
    2016 Coordination of self-renewal in glioblastoma by integration of adhesion and microRNA signaling 2016
    2016 G-quadruplex ligand-induced DNA damage response coupled with telomere dysfunction and replication stress in glioma stem cells 2016
    2016 Predictors of impaired communication in amyotrophic lateral sclerosis patients with tracheostomy-invasive ventilation 2016
    2016 Serine/Threonine Kinase MLK4 Determines Mesenchymal Identity in Glioma Stem Cells in an NF-κB-dependent Manner 2016
    2016 Senescence from glioma stem cell differentiation promotes tumor growth 2016
    2016 Correction: Pigment Epithelium-Derived Factor (PEDF) Expression Induced by EGFRvIII Promotes Self-renewal and Tumor Progression of Glioma Stem Cells. 2016
    2015 Histone deacetylase 6 inhibition enhances oncolytic viral replication in glioma 2015
    2015 The LIM-only transcription factor LMO2 determines tumorigenic and angiogenic traits in glioma stem cells 2015
    2015 Gene expression profiling distinguishes proneural glioma stem cells from mesenchymal glioma stem cells 2015
    2015 Dynamic epigenetic regulation of glioblastoma tumorigenicity through LSD1 modulation of MYC expression 2015
    2015 CAR-engineered NK cells targeting wild-type EGFR and EGFRvIII enhance killing of glioblastoma and patient-derived glioblastoma stem cells 2015
    2015 Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma 2015
    2015 miRNA contents of cerebrospinal fluid extracellular vesicles in glioblastoma patients 2015
    2015 Pigment Epithelium-Derived Factor (PEDF) Expression Induced by EGFRvIII Promotes Self-renewal and Tumor Progression of Glioma Stem Cells 2015
    2015 Kinome-wide shRNA screen identifies the receptor tyrosine kinase AXL as a key regulator for mesenchymal glioblastoma stem-like cells 2015
    2015 Extracellular vesicles in the biology of brain tumour stem cells - Implications for inter-cellular communication, therapy and biomarker development 2015
    2015 Stem cell signature in glioblastoma: Therapeutic development for a moving target 2015
    2015 EZH2 protects Glioma stem cells from radiation-induced cell death in a MELK/FOXM1-dependent manner 2015
    2015 MELK-a conserved kinase: functions, signaling, cancer, and controversy. 2015
    2015 RNA nanoparticle as a vector for targeted siRNA delivery into glioblastoma mouse model 2015
    2015 Ras-mediated modulation of pyruvate dehydrogenase activity regulates mitochondrial reserve capacity and contributes to glioblastoma tumorigenesis 2015
    2015 SIRT1 is required for oncogenic transformation of neural stem cells and for the survival of "cancer cells with neural stemness" in a p53-dependent manner 2015
    2015 Strong therapeutic potential of γ-secretase inhibitor MRK003 for CD44-high and CD133-low glioblastoma initiating cells 2015
    2015 Targeted delivery of tumor suppressor microRNA-1 by transferrin-conjugated lipopolyplex nanoparticles to patient-derived glioblastoma stem cells 2015
    2014 Neuronal ceroid lipofuscinosis genes, CLN2, CLN3 and CLN5 are spatially and temporally co-expressed in a developing mouse brain 2014
    2014 Crosstalk between glioma-initiating cells and endothelial cells drives tumor progression 2014
    2014 Multi-kinase inhibitor c1 triggers mitotic catastrophe of glioma stem cells mainly through melk kinase inhibition 2014
    2014 Multi-kinase inhibitor C1 triggers mitotic catastrophe of Glioma stem cells mainly through MELK kinase inhibition 2014
    2014 Extracellular vesicles modulate the glioblastoma microenvironment via a tumor suppression signaling network directed by miR-1 2014
    2014 Genomic analyses reveal broad impact of miR-137 on genes associated with malignant transformation and neuronal differentiation in glioblastoma cells 2014
    2014 Detoxification of oxidative stress in glioma stem cells: Mechanism, clinical relevance, and therapeutic development 2014
    2014 EGFR phosphorylation of DCBLD2 recruits TRAF6 and stimulates AKT-promoted tumorigenesis 2014
    2014 Engulfing losers by winners in cancer: Do cancer stem cells catch eat-me signals from noncancer stem cells? 2014
    2014 Ethics of iPSC-Based Clinical Research for Age-Related Macular Degeneration: Patient-Centered Risk-Benefit Analysis 2014
    2014 High-throughput flow cytometry screening reveals a role for junctional adhesion molecule a as a cancer stem cell maintenance factor 2014
    2014 Intercellular cooperation and competition in brain cancers: Lessons from Drosophila and human studies 2014
    2014 Maternal embryonic leucine zipper kinase: Key kinase for stem cell phenotype in glioma and other cancers 2014
    2014 Piperlongumine treatment inactivates peroxiredoxin 4, exacerbates endoplasmic reticulum stress, and preferentially kills high-grade glioma cells 2014
    2014 Proneural-mesenchymal transformation of glioma stem cells: Do therapies cause evolution of target in glioblastoma? 2014
    2014 The AMPK inhibitor compound C is a potent AMPK-independent antiglioma agent 2014
    2014 Therapeutic potential of targeting glucose metabolism in glioma stem cells 2014
    2014 Transcription factors as master regulator for cancer stemness: Remove milk from fox? 2014
    2014 Tumoral RANKL activates astrocytes that promote glioma cell invasion through cytokine signaling 2014
    2013 miR-21 in the Extracellular Vesicles (EVs) of Cerebrospinal Fluid (CSF): A Platform for Glioblastoma Biomarker Development 2013
    2013 Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake 2013
    2013 Mesenchymal Differentiation Mediated by NF-κB Promotes Radiation Resistance in Glioblastoma 2013
    2013 MicroRNA-128 coordinately targets Polycomb Repressor Complexes in glioma stem cells 2013
    2013 Phosphorylation of EZH2 Activates STAT3 Signaling via STAT3 Methylation and Promotes Tumorigenicity of Glioblastoma Stem-like Cells 2013
    2013 MELK-dependent FOXM1 phosphorylation is essential for proliferation of glioma stem cells 2013
    2013 Mesenchymal glioma stem cells are maintained by activated glycolytic metabolism involving aldehyde dehydrogenase 1A3 2013
    2013 Tumor-specific activation of the C-JUN/MELK pathway regulates glioma stem cell growth in a p53-dependent manner 2013
    2013 Overview of brain tumor stem cells - Implications for treatment 2013
    2013 Impairment of glioma stem cell survival and growth by a novel inhibitor for survivin-ran protein complex 2013
    2013 Blockade of EGFR signaling promotes glioma stem-like cell invasiveness by abolishing ID3-mediated inhibition of p27KIP1 and MMP3 expression 2013
    2013 A streamlined protocol for the use of the semi-sitting position in neurosurgery: A report on 48 consecutive procedures 2013
    2012 Fluorescence-guided brain tumor surgery 2012
    2012 Laminin alpha 2 enables glioblastoma stem cell growth 2012
    2012 Characteristics of brain tumor stem cells and the rationale for applying tyrosine kinase inhibitors as potential targeting agents 2012
    2012 Therapeutic targeting of VEGF in the treatment of glioblastoma 2012
    2012 Suppression of peroxiredoxin 4 in glioblastoma cells increases apoptosis and reduces tumor growth 2012
    2012 Telomestatin impairs glioma stem cell survival and growth through the disruption of telomeric G-quadruplex and inhibition of the proto-oncogene, c-Myb 2012
    2012 Glioma Stem Cells and their Therapy Resistance 2012
    2012 Glioma stem cells: Their role in chemoresistance 2012
    2012 Hope and challenges for dendritic cell-based vaccine therapy for glioblastoma 2012
    2011 A molecular screening approach to identify and characterize inhibitors of glioblastoma stem cells 2011
    2011 CD44V6 regulates growth of brain tumor stem cells partially through the AKT-mediated pathway 2011
    2011 Method for novel anti-cancer drug development using tumor explants of surgical specimens 2011
    2011 Siomycin A targets brain tumor stem cells partially through a MELK-mediated pathway 2011
    2011 Finding drugs against CD133+ glioma subpopulations 2011
    2010 Cancer stem cells in malignant glioma - The mechanism of cancer initiation and the therapeutic development 2010
    2010 Cancers and Cancer Stem Cells 2010
    2009 Cancer stem cells in pediatric brain tumors 2009
    2009 Methods for analysis of brain tumor stem cell and neural stem cell self-renewal. 2009
    2008 BMPing Off Glioma Stem Cells 2008
    2008 Maternal embryonic leucine zipper kinase is a key regulator of the proliferation of malignant brain tumors, including brain tumor stem cells 2008
    2007 Phosphoserine phosphatase is expressed in the neural stem cell niche and regulates neural stem and progenitor cell proliferation 2007
    2006 Brain tumor stem cells 2006
    2006 Phenotypic and functional heterogeneity of GFAP-expressing cells in vitro: Differential expression of LeX/CD15 by GFAP-expressing multipotent neural stem cells and non-neurogenic astrocytes 2006
    2005 PBK/TOPK, a proliferating neural progenitor-specific mitogen-activated protein kinase kinase 2005
    2005 Maternal embryonic leucine zipper kinase (MELK) regulates multipotent neural progenitor proliferation 2005
    2004 Developmental expression of glial fibrillary acidic protein mRNA in mouse forebrain germinal zones - Implications for stem cell biology 2004
    2004 Cancer stem cell in pediatric brain tumor 2004
    2004 Patterns of Jagged1, Jagged2, Delta-Like 1 and Delta-Like 3 Expression during Late Embryonic and Postnatal Brain Development Suggest Multiple Functional Roles in Progenitors and Differentiated Cells 2004
    2003 Neural progenitor genes: Germinal zone expression and analysis of genetic overlap in stem cell populations 2003
    2003 Cancerous stem cells can arise from pediatric brain tumors 2003
    2003 Stem cell-derived neural stem/progenitor cell supporting factor is an autocrine/paracrine survival factor for adult neural stem/progenitor cells 2003
    2000 Incorporation and differentiation of hippocampus-derived neural stem cells transplanted in injured adult rat retina 2000
    1997 Choroid plexus papilloma in the posterior third ventricle: Case report 1997
    1996 Solitary metastatic breast carcinoma in a trigeminal nerve mimicking a trigeminal neurinoma: Case report 1996
    1995 Treatment of intractable postherpetic neuralgia and blepharospasm: Intraneural injection of adriamycin 1995


    Year Title Altmetric
    2009 Self-Renewal Signaling Pathways in Neural Stem Cells and Brain Tumor Stem Cells.  37-56. 2009
    2003 Stage-Specific and Cell Fate Markers.  95-126. 2003

    Research Overview

  • Clinical trials for malignant brain tumors
  • Principal Investigator On

  • Brain Tumor Recurrence Via Signals From Vascular Endothelial Cells  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS 2019 - 2024
  • Radiation-Induced Crosstalk of Immune and Glioma Stem Cells  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS 2019 - 2024
  • The Roles of a Unique GTP-Binding Protein/Crosslinking Enzyme in Disease  awarded by Cornell University 2015 - 2020
  • Glioblastoma Phenotype Modulation through miRNA Control of Wnt Signaling  awarded by Northwestern University 2015 - 2020
  • Novel Role of Compensatory Proliferation in Human Brain Tumor  awarded by National Cancer Institute/NIH/DHHS 2016 - 2020
  • STAT3, G6PD AND TRxR as Underlying Mechanisms for Antitumor Responses to Hirsutinolides  awarded by UNIVERSITY OF HAWAII CANCER CENTER 2019
  • Metabolism Informs lntertumoral & lntratumoral Heterogeneity  awarded by University of California, San Diego 2017 - 2019
  • Targeting MELK-Mediated EZH2 Signaling in Glioma Stem Cells  awarded by National Institute of Neurological Disorders and Stroke/NIH/DHHS 2015 - 2018
  • Novel Adhesion Mechanism in Glioblastoma Stem Cells  awarded by CLEVELAND CLINIC LERNER RESEARCH INSTITUTE 2015 - 2018
  • Novel Role of the Polycomb Repressive Complex PRC2/EZH2 in Glioblastoma  awarded by University of Texas at Austin 2016 - 2018
  • Metabolism Informs lntertumoral & lntratumoral Heterogeneity  awarded by CLEVELAND CLINIC LERNER RESEARCH INSTITUTE 2015 - 2017
  • Determination of Mussashi 1/CD44v6 Signaling in Mesenchymal Glioma Stem Cells  awarded by National Cancer Institute/NIH/DHHS 2016
  • Education And Training

  • University of California Los Angeles Departments of Surgery and Pediatrics, Other 2009
  • Kishiwada City Hospital (affiliated to Kyoto University School of Medicine) Department of Neurosurgery, Other 2001
  • Doctor of Philosophy in Biomedical Sciences, Kyoto University 2001
  • Kyoto University School of Medicine, Other 2001
  • Doctor of Medicine, Kyoto University 1993
  • Kyoto University School of Medicine, Residency 2001
  • Kyoto University School of Medicine Department of Neurosurgery, Residency 1997
  • Tukaguchi Hospital (affiliated to Kyoto University School of Medicine) Department of Neurosurgery, Residency 1997
  • Kitano Hospital (affiliated to Kyoto University School of Medicine) Department of Neurosurgery, Residency 1996
  • Ohio State University, Postdoctoral Fellowship 2012
  • Ohio State University Department of Neuro-Oncology Surgery, Postdoctoral Fellowship 2012
  • UCLA, Postdoctoral Fellowship 2009
  • UCLA, Postdoctoral Fellowship 2005
  • Full Name

  • Ichiro Nakano