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