Department of Cell Biology, Nagoya City University Graduate School of Medical Sciences

Last updated: 08/08/2022
img Associate professor

Issei S. Shimada, Ph.D.


Mail: ishimadaids

Academic Experience & Education

Aug 2018 - Today Junior Associate Professor, Graduate School of Medical Sciences, Department of Cell Biology, Nagoya City University
Jan 2015 - Jul 2018 Assistant Instructor, Department of Cell Biology,
University of Texas Southwestern Medical School
Aug 2011 - Dec 2014 Post-doc, University of Texas Southwestern Medical School
Apr 2010 - Jul 2011 Post-doc, Department of Medicine, University of Vermont, Graduate School
Aug 2005 - May 2010 Department of Anatomy and Neurobiology, College of Medicine, University of Vermont, Graduate School
Apr 2002 - Mar 2004 Life Science, Department of Science, University of Hyogo, Graduate School
Apr 1998 - Mar 2002 Life Science, Department of Science, University of Hyogo

Research Focus

  •  Our fundamental object is to elucidate the mechanisms that regulate neural stem cells and brain development. Neural stem cells have capacities to do self-renewing divisions to increase the number of stem cells, and to do multipotent differentiation to generate neurons, astrocytes, oligodendrocytes and ependymal cells. It has been shown that inappropriate neural stem cell function induced various brain diseases, such as neurodevelopmental disorders and cancers. We aim to figure out the mechanisms of neural stem cell regulation by focusing one cellular organelle called primary cilia.

  • Primary cilia are cell organelles specialized for signal compartments
  •  Primary cilia are antenna-like organelles that are present in almost all cells in our body. Primary cilia are enriched in G-protein-coupled receptors (GPCRs), ion channels, and transmembrane proteins, and therefore function as signaling compartments. Abnormalities in the formation and function of primary cilia cause a group of diseases called ciliopathies. Symptoms of ciliopathies are tissue-dependent, such as intellectual disability, renal cysts, visceral inversion, polydactyly, and retinitis pigmentosa. We aim to elucidate how primary ciliary signaling regulates neural stem cell functions during brain development.

  • Gpr161 prevents medulloblastoma formation
  •  We aimed to investigate how primary ciliary signaling regulates neural stem cells. G protein coupled receptor 161 (GPR161) is an orphan receptor localized in primary cilia. We have generated brain specific Gpr161 cKO mice (Nestin-Cre; Gpr161fl/fl conditional KO mice). The loss of Gpr161 in neural stem cells generated medulloblastoma in the cerebellum of mice. We have also shown that deletion of Gpr161 enhanced Sonic Hedgehog (Shh) signaling pathway, and activate neural stem cells in primary cilia dependent manner. Furthermore, we have shown that low expression level of GPR161 correlates with poor prognosis in Shh-subtype medulloblastoma patients. These data indicate that Gpr161 is one of the critical ciliary signaling components for stem cell function and tumorigenesis.

  • Gpr161 regulates cortical formation
  •  We aimed to investigate how primary ciliary signaling regulates brain development. Gpr161 cKO mice were born with hydrocephalus, polymicrogyria in the medial cingulate cortex and periventricular nodular heterotopia, indicating dysregulated neurogenesis during embryonic development. We have shown that the loss of Gpr161 resulted in enhanced differentiation of neural stem cells into outer radial glia and increased neurogenesis. In addition, we have shown that Gpr161 regulates the Shh signaling pathway through the Gli3 transcription factor, which in turn regulates neuronal migration and differentiation in the cerebral cortex. These data indicate that Gpr161 is one of the critical ciliary signaling components for cortical formation.

  • Our current projects
  •  We are currently studying how primary ciliary signaling regulates neural stem cells using iPS cell derived brain organoids.


Published Papers

  • Nakamura Y, Shimada IS, Maroofian R, Falabella M, Zaki MS, Fujimoto M, Sato E, Takase H, Aoki S, Miyauchi A, Koshimizu E, Miyatake S, Arioka Y, Honda M, Higashi T, Miya F, Okubo Y, Ogawa I, Scardamaglia A, Miryounesi M, Alijanpour S, Ahmadabadi F, Herkenrath P, Dafsari HS, Velmans C, Al Balwi M, Vitobello A, Denommé-Pichon AS, Jeanne M, Civit A, Abdel-Hamid MS, Naderi H, Darvish H, Bakhtiari S, Kruer MC, Carroll CJ, Ghayoor Karimiani E, Khailany RA, Abdulqadir TA, Ozaslan M, Bauer P, Zifarelli G, Seifi T, Zamani M, Al Alam C, Alvi JR, Sultan T, Efthymiou S, Pope SAS, Haginoya K, Matsunaga T, Osaka H, Matsumoto N, Ozaki N, Ohkawa Y, Oki S, Tsunoda T, Pitceathly RDS, Taketomi Y, Houlden H, Murakami M, Kato Y, Saitoh S.
    Biallelic null variants in PNPLA8 cause microcephaly by reducing the number of basal radial glia.
    Brain, 2024 Nov 4;147(11):3949-3967.

  • Earwood R, Ninomiya H, Wang H, Shimada IS, Stroud M, Perez D, Uuganbayar U, Yamada C, Akiyama-Miyoshi T, Stefanovic B, Kato Y.
    The binding of LARP6 and DNAAF6 in biomolecular condensates influences ciliogenesis of multiciliated cells.
    Journal of Biological Chemistry, 2024 Jun;300(6):107373.

  • Shimada IS, Kato Y.
    Ciliary signaling in stem cells in health and disease: Hedgehog pathway and beyond.
    Seminars in Cell and Developmental Biology, 2022 Apr 21;S1084-9521(22)00135-5.

  • Shimada IS, Somatilaka BN, Hwang SH, Anderson AG, Shelton JM, Rajaram V, Konopka G, Mukhopadhyay S.
    Derepression of sonic hedgehog signaling upon Gpr161 deletion unravels forebrain and ventricular abnormalities.
    Developmental Biology, 2019 Jun 1;450(1):47-62.

  • Shimada IS, Hwang SH, Somatilaka BN, Wang X, Skowron P, Kim J, Kim M, Shelton JM, Rajaram V, Xuan Z, Taylor MD, Mukhopadhyay S.
    Basal Suppression of the Sonic Hedgehog Pathway by the G-Protein-Coupled Receptor Gpr161 Restricts Medulloblastoma Pathogenesis.
    Cell Reports, 2018 Jan 30;22(5):1169-1184.

  • Shimada IS, Acar M, Burgess RJ, Zhao Z, Morrison SJ.
    Prdm16 is required for the maintenance of neural stem cells in the postnatal forebrain and their differentiation into ependymal cells.
    Genes & development, 2017 Jun;31(11):1134-1146

  • Shimada IS, Badgandi H, Somatilaka BN, Mukhopadhyay S.
    Using Primary Neurosphere Cultures to Study Primary Cilia.
    Journal of visualized experiments : JoVE, 2017 Apr;(122)

  • Badgandi HB, Hwang SH, Shimada IS, Loriot E, Mukhopadhyay S.
    Tubby family proteins are adapters for ciliary trafficking of integral membrane proteins.
    The Journal of cell biology, 2017 Mar;216(3):743-760

  • Shimada IS, Mukhopadhyay S.
    G-protein-coupled receptor signaling and neural tube closure defects.
    Birth defects research, 2017 Jan;109(2):129-139

  • Mukhopadhyay S, Badgandi HB, Hwang SH, Somatilaka B, Shimada IS, Pal K.
    Trafficking to the primary cilium membrane.
    Molecular biology of the cell, 2017 Jan;28(2):233-239

  • Yue R, Zhou BO, Shimada IS, Zhao Z, Morrison SJ.
    Leptin Receptor Promotes Adipogenesis and Reduces Osteogenesis by Regulating Mesenchymal Stromal Cells in Adult Bone Marrow.
    Cell stem cell, 2016 Jun;18(6):782-796

  • LeComte MD, Shimada IS, Sherwin C, Spees JL.
    Notch1-STAT3-ETBR signaling axis controls reactive astrocyte proliferation after brain injury.
    Proc. Natl. Acad. Sci. USA, 2015 Jul;112(28):8726-8731

  • Shimada IS, LeComte MD, Granger JC, Quinlan NJ, Spees JL.
    Self-renewal and differentiation of reactive astrocyte-derived neural stem/progenitor cells isolated from the cortical peri-infarct area after stroke.
    The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012 Jun;32(23):7926-7940

  • Shimada IS, Borders A, Aronshtam A, Spees JL.
    Proliferating reactive astrocytes are regulated by Notch-1 in the peri-infarct area after stroke.
    Stroke, 2011 Nov;42(11):3231-3237

  • Bakondi B, Shimada IS, Peterson BM, Spees JL.
    SDF-1α secreted by human CD133-derived multipotent stromal cells promotes neural progenitor cell survival through CXCR7.
    Stem cells and development, 2011 Jun;20(6):1021-1029

  • Shimada IS, Spees JL.
    Stem and progenitor cells for neurological repair: minor issues, major hurdles, and exciting opportunities for paracrine-based therapeutics.
    Journal of cellular biochemistry, 2011 Feb;112(2):374-380

  • Shimada IS, Peterson BM, Spees JL.
    Isolation of locally derived stem/progenitor cells from the peri-infarct area that do not migrate from the lateral ventricle after cortical stroke.
    Stroke, 2010 Sep;41(9):e552-60

  • Bakondi B, Shimada IS, Perry A, Munoz JR, Ylostalo J, Howard AB, Gregory CA, Spees JL.
    CD133 identifies a human bone marrow stem/progenitor cell sub-population with a repertoire of secreted factors that protect against stroke.
    Molecular therapy : the journal of the American Society of Gene Therapy, 2009 Nov;17(11):1938-1947

  • Fraley GS, Scarlett JM, Shimada I, Teklemichael DN, Acohido BV, Clifton DK, Steiner RA.
    Effects of diabetes and insulin on the expression of galanin-like peptide in the hypothalamus of the rat.
    Diabetes, 2004 May;53(5):1237-1242

  • Kusakabe T, Mishima S, Shimada I, Kitajima Y, Tsuda M.
    Structure, expression, and cluster organization of genes encoding gonadotropin-releasing hormone receptors found in the neural complex of the ascidian Ciona intestinalis.
    Gene, 2003 Dec;322:77-84

  • Fraley GS, Shimada I, Baumgartner JW, Clifton DK, Steiner RA.
    Differential patterns of Fos induction in the hypothalamus of the rat following central injections of galanin-like peptide and galanin.
    Endocrinology, 2003 Apr;144(4):1143-1146