Laboratories

Functional Genomics and Medicine

Assoc. Prof. Ishida
Associate Professor
Yasumasa ISHIDA
Assistant Professor
Nanaho FUKUDA
Labs HP
http://bsw3.naist.jp/ishida/?cate=431

Outline of Research and Education

Since completion of the genome sequencing of a variety of organisms including mice and humans, a main task has become elucidating the functions of the sequenced genomes. For this purpose, biomedical researchers inactivate particular genes of interest in mice and analyze the phenotypes of the mutated animals, thereby revealing the functions of the inactivated genes. We will devote our efforts to the investigation on the higher cognitive functions in the immune and nervous systems in mice and humans.

Major Research Topics

Elucidation of the physiological functions of PD-1

Since the discovery of PD-1 by Y. Ishida et al. in 1992, the negative immuno-regulatory functions of the PD-1 molecules expressed on the surface of activated T lymphocytes have been described. Recently, cancer immunotherapy based on the blockade of the PD-1 pathway has been successfully performed in clinics (Cell 162, 937, 2015). We try to elucidate the yet undiscovered functions of PD-1 in the self-nonself discrimination of the immune system.

mRNA localization in mouse sensory neurons

mRNA localization is a widely employed mechanism to target protein synthesis to specific cellular sites. It is particularly important for neuronal development and function. In mammalian olfactory sensory neurons, odorant receptor (OR) mRNAs are localized in the axon terminal. We currently investigate the molecular mechanisms of the OR mRNA localization in mouse olfactory sensory neurons and we have revealed the involvement of RNA binding proteins. We also explore how mRNA localization contributes to physiological functions and/or development of the olfactory tissue by using transgenic and knockout mouse models.

Development of novel gene-trapping strategies

Previously, it was almost impossible to inactivate transcriptionally silent genes in ES cells by random gene trapping. Almost 10 years ago, we developed a novel gene-trapping strategy named UPATrap that is based on the suppression of NMD, and allows for such difficult gene disruption for the first time. We are upgrading the UPATrap technology in order to randomly disrupt long non-coding mRNA genes as well as protein-coding ones. We also produce mutant mice using newly developed techniques and analyze their phenotypes.

References

  1. Nakamura A. et al. Neurosci. Res. 100, 55-62, 2015
  2. Fukuda N. et al, Plos Genet. 9, e1003858, 2013
  3. Shigeoka T. et al. Nucleic Acids Res. 40, 6887-6897, 2012
  4. Mayasari N. I. et al. Nucleic Acids Res. 40, e97, 2012
  5. Raju C. Fukuda N. et al, Mol. Biol. Cell 1, 1864-1877, 2011
  6. Shigeoka T. et al. Nucleic Acids Res. 33, e20, 2005
  7. Fukuda N. et al. J. Cell Sci. 117, 5835-5845, 2004
  8. Matsuda E. et al. Proc. Natl. Acad. Sci. USA 101, 4170-4174, 2004
  9. Ishida Y. and Leder, P. Nucleic Acids Res. 27, e35, 1999
  10. Ishida Y. et al. EMBO J. 11, 3887-3895, 1992
Fig. 1 Modulation of the PD-1 activity leads to effective T-cell immunity against cancer cells
Fig. 1 Modulation of the PD-1 activity leads to effective T-cell immunity against cancer cells
Fig. 2  Immunostaining of an RNA binding protein on the section of mouse olfactory tissue. We have found that some RNA binding proteins are highly enriched in the glomeruli of the olfactory bulb, where the axon terminal of olfactory sensory neurons exist.
Fig. 2  Immunostaining of an RNA binding protein on the section of mouse olfactory tissue. We have found that some RNA binding proteins are highly enriched in the glomeruli of the olfactory bulb, where the axon terminal of olfactory sensory neurons exist.
Fig. 3 The UPATrap method for the random insertional mutagenesis of transcriptionally silent genes in target cells.
Fig. 3 The UPATrap method for the random insertional mutagenesis of transcriptionally silent genes in target cells.
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