Akihide TAKEUCHI MD, PhD

Research & Professional Experience

Akihide Takeuchi took MD in Nagoya University School of Medicine, Nagoya, Japan, obtained the medical license, and had training as a neurosurgeon for several years. He got Ph.D. at Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

His research interests are deciphering the regulatory mechanism of brain development through understanding gene regulation. He got post-doctoral training in National Center for Geriatrics and Gerontology National Center for Geriatrics and Gerontology, Obu, Aichi, Japan. There he found essential transcription factor that regulates the development of germ cells and neurogenesis by generating gene targeting mouse (Takeuchi et al, Nat Genet 2003, Kojima et al, FASEB J 2003). To further deeply learn about neuronal development, he got training at the Salk Institute for Biological Studies, La Jolla, California U.S.A. under the supervision of Dr. Dennis DM O’Leary. These he found essential regulation of corticogenesis (Takeuchi and O’Leary, J Neurosci 2006, Takeuchi et al, Cereb Cortex 2006).

From 2006, he joined to Dr. Hagiwara’s lab and focused on deciphering the regulatory mechanism of gene expression including mRNA regulation. For this purpose, he developed mammalian splicing reporter system that enables real time visualization of mRNA regulation in vivo (Takeuchi et al, PLoS One 2010). This system is quite useful for analyzing the regulatory mechanism of mRNA metabolism in normal also disease conditions caused by genetic mutations, thus he patented with Dr. Hagiwara in Japan, US and Europe. Splicing reporter system was applied to develop novel therapeutic method manipulating mRNA regulation with small chemicals to cure genetic diseases (Yoshida et al. PNAS 2015, and other RNA diseases are currently on going).

Next he moved his focus to analyze the functions of RNA-binding proteins (RBPs) those are essential for neuronal or muscular development. He identified several cell-type specific RBPs and analyzed their functions from in vitro to in vivo using CLIP for the purposes of large-scale mapping of protein-RNA interactions and also gene targeting mice for phenotypic analyses. From combining comprehensive analyses, he revealed that RNA-binding proteins play essential roles in neuronal development or muscle growth through regulating the transcriptome of functional gene clusters (Takeuchi et al, Cell Rep 2018, Hosokawa et al, iScience 2019, Iida et al, iScience 2020, Takeuchi et al, Stem Cell Rep 2020).

In 2021, he elected as the Professor & Chairperson of newly established department, "Department of Anatomy and Histology" at Ehime University Graduate School of Medicine in Japan, and started his own laboratory.

Publication

1          Takeuchi, A., Takahashi, Y., Iida, K., Hosokawa, M., Irie, K., Ito, M., Brown, J. B., Ohno, K., Nakashima, K. & Hagiwara, M. Identification of Qk as a Glial Precursor Cell Marker that Governs the Fate Specification of Neural Stem Cells to a Glial Cell Lineage. Stem Cell Reports 15, 883-897, doi:10.1016/j.stemcr.2020.08.010 (2020).

2          Iida, K., Hagiwara, M. & Takeuchi, A. Multilateral Bioinformatics Analyses Reveal the Function-Oriented Target Specificities and Recognition of the RNA-Binding Protein SFPQ. iScience 23, 101325, doi:10.1016/j.isci.2020.101325 (2020).

3          Kurokawa, R., Takeuchi, A., Shiina, N., Katahira, M., Yamashita, T., Matsuno, Y., Hitachi, K., Ishigaki, S., Haamad, N., Yoneda, R., Ueda, N., Iida, K., Hosokawa, M., Hagiwara, M., Iida, M., Mashima, T., Yamaoki, Y., So, M., Nagata, T., Sobue, G., Kondo, K., Watanabe, H. & Uchihashi, T. Versatility of RNA-Binding Proteins in Living Cells. Biomedical Sciences 5, 7-13, doi:10.11648/j.bs.20190501.12 (2019).

4          Hosokawa, M., Takeuchi, A., Tanihata, J., Iida, K., Takeda, S. & Hagiwara, M. Loss of RNA-Binding Protein Sfpq Causes Long-Gene Transcriptopathy in Skeletal Muscle and Severe Muscle Mass Reduction with Metabolic Myopathy. iScience 13, 229-242, doi:10.1016/j.isci.2019.02.023 (2019).

5          Takeuchi, A., Iida, K., Tsubota, T., Hosokawa, M., Denawa, M., Brown, J. B., Ninomiya, K., Ito, M., Kimura, H., Abe, T., Kiyonari, H., Ohno, K. & Hagiwara, M. Loss of Sfpq Causes Long-Gene Transcriptopathy in the Brain. Cell Rep 23, 1326-1341, doi:10.1016/j.celrep.2018.03.141 (2018).

6          Yoshida, M., Kataoka, N., Miyauchi, K., Ohe, K., Iida, K., Yoshida, S., Nojima, T., Okuno, Y., Onogi, H., Usui, T., Takeuchi, A., Hosoya, T., Suzuki, T. & Hagiwara, M. Rectifier of aberrant mRNA splicing recovers tRNA modification in familial dysautonomia. Proceedings of the National Academy of Sciences, USA 112, 2764-2769, doi:10.1073/pnas.1415525112 (2015).

7          Ohnishi, T., Yanazawa, M., Sasahara, T., Kitamura, Y., Hiroaki, H., Fukazawa, Y., Kii, I., Nishiyama, T., Kakita, A., Takeda, H., Takeuchi, A., Arai, Y., Ito, A., Komura, H., Hirao, H., Satomura, K., Inoue, M., Muramatsu, S., Matsui, K., Tada, M., Sato, M., Saijo, E., Shigemitsu, Y., Sakai, S., Umetsu, Y., Goda, N., Takino, N., Takahashi, H., Hagiwara, M., Sawasaki, T., Iwasaki, G., Nakamura, Y., Nabeshima, Y., Teplow, D. B. & Hoshi, M. Na, K-ATPase alpha3 is a death target of Alzheimer patient amyloid-beta assembly. Proceedings of the National Academy of Sciences, USA 112, E4465-4474, doi:10.1073/pnas.1421182112 (2015).

8          Sims-Lucas, S., Cusack, B., Baust, J., Eswarakumar, V. P., Masatoshi, H., Takeuchi, A. & Bates, C. M. Fgfr1 and the IIIc isoform of Fgfr2 play critical roles in the metanephric mesenchyme mediating early inductive events in kidney development. Developmental Dynamics 240, 240-249, doi:10.1002/dvdy.22501 (2011).

9          Takeuchi, A., Hosokawa, M., Nojima, T. & Hagiwara, M. Splicing reporter mice revealed the evolutionally conserved switching mechanism of tissue-specific alternative exon selection. PLoS One 5, e10946, doi:10.1371/journal.pone.0010946 (2010).

10        Takeuchi, A., Hamasaki, T., Litwack, E. D. & O'Leary, D. D. Novel IgCAM, MDGA1, expressed in unique cortical area- and layer-specific patterns and transiently by distinct forebrain populations of Cajal-Retzius neurons. Cerebral Cortex 17, 1531-1541, doi:bhl064 [pii]

10.1093/cercor/bhl064 (2007).

11        O'Leary, D. D., Chou, S. J., Hamasaki, T., Sahara, S., Takeuchi, A., Thuret, S. & Leingartner, A. Regulation of laminar and area patterning of mammalian neocortex and behavioural implications. Novartis Foundation Symposium 288, 141-159; discussion 159-164, 276-181 (2007).

12        Takeuchi, A. & O'Leary, D. D. Radial migration of superficial layer cortical neurons controlled by novel Ig cell adhesion molecule MDGA1. Journal of Neuroscience 26, 4460-4464, doi:26/17/4460 [pii]

10.1523/JNEUROSCI.4935-05.2006 (2006).

13        Takeuchi, A., Mishina, Y., Miyaishi, O., Kojima, E., Hasegawa, T. & Isobe, K. Heterozygosity with respect to Zfp148 causes complete loss of fetal germ cells during mouse embryogenesis. Nature Genetics 33, 172-176, doi:10.1038/ng1072

ng1072 [pii] (2003).

14        Kojima, E., Takeuchi, A., Haneda, M., Yagi, A., Hasegawa, T., Yamaki, K., Takeda, K., Akira, S., Shimokata, K. & Isobe, K. The function of GADD34 is a recovery from a shutoff of protein synthesis induced by ER stress: elucidation by GADD34-deficient mice. FASEB Journal 17, 1573-1575, doi:10.1096/fj.02-1184fje

02-1184fje [pii] (2003).

15        Takeuchi, A., Miyaishi, O., Kiuchi, K. & Isobe, K. Macrophage colony-stimulating factor is expressed in neuron and microglia after focal brain injury. Journal of Neuroscience Research 65, 38-44 (2001).

16        Takeuchi, A., Miyaishi, O., Kiuchi, K. & Isobe, K. Cu/Zn- and Mn-superoxide dismutases are specifically up-regulated in neurons after focal brain injury. Journal of Neurobiology 45, 39-46, doi:10.1002/1097-4695(200010)45:1<39::AID-NEU4>3.0.CO;2-A [pii] (2000).

17        Hasegawa, T., Takeuchi, A., Miyaishi, O., Xiao, H., Mao, J. & Isobe, K. PTRF (polymerase I and transcript-release factor) is tissue-specific and interacts with the BFCOL1 (binding factor of a type-I collagen promoter) zinc-finger transcription factor which binds to the two mouse type-I collagen gene promoters. Biochemical Journal 347 Pt 1, 55-59 (2000).

18        Maehara, K., Hasegawa, T., Xiao, H., Takeuchi, A., Abe, R. & Isobe, K. Cooperative interaction of NF-kappaB and C/EBP binding sites is necessary for manganese superoxide dismutase gene transcription mediated by lipopolysaccharide and interferon-gamma. FEBS Letters 449, 115-119, doi:S0014579399004081 [pii] (1999).

19        Takeuchi, A., Isobe, K. I., Miyaishi, O., Sawada, M., Fan, Z. H., Nakashima, I. & Kiuchi, K. Microglial NO induces delayed neuronal death following acute injury in the striatum. European Journal of Neuroscience 10, 1613-1620 (1998).

20        Yamada, E., Ishiguro, N., Miyaishi, O., Takeuchi, A., Nakashima, I., Iwata, H. & Isobe, K. Differential display analysis of murine collagen-induced arthritis: cloning of the cDNA-encoding murine ATPase inhibitor. Immunology 92, 571-576 (1997).

21        Nozaki, Y., Hasegawa, Y., Takeuchi, A., Fan, Z. H., Isobe, K. I., Nakashima, I. & Shimokata, K. Nitric oxide as an inflammatory mediator of radiation pneumonitis in rats. American Journal of Physiology: Lung Cellular and Molecular Physiology 272, L651-658 (1997).

22        Hasegawa, T., Takeuchi, A., Miyaishi, O., Isobe, K. & de Crombrugghe, B. Cloning and characterization of a transcription factor that binds to the proximal promoters of the two mouse type I collagen genes. Journal of Biological Chemistry 272, 4915-4923 (1997).

23        Aono, K., Isobe, K., Kiuchi, K., Fan, Z. H., Ito, M., Takeuchi, A., Miyachi, M., Nakashima, I. & Nimura, Y. In vitro and in vivo expression of inducible nitric oxide synthase during experimental endotoxemia: involvement of other cytokines. Journal of Cellular Biochemistry 65, 349-358, doi:10.1002/(SICI)1097-4644(19970601)65:3<349::AID-JCB5>3.0.CO;2-S [pii] (1997).