Yasunori Hayashi: Difference between revisions

From Welcome to Yasunori Hayashi Laboratory
Jump to navigation Jump to search
← Older editNewer edit →
Yasunorihayashi (talk | contribs)
Bureaucrats, Interface administrators, Administrators
72 edits
Line 28: Line 28:
Prostanoids include prostaglandins and other metabolites of arachidonic acid. Based on the partial amino acid sequence of the thromboxane A2 receptor protein purified in the Narumiya laboratory at Kyoto University, we cloned the full-length cDNA from a human placental cDNA library<ref group="2"><pubmed>1825698</pubmed></ref><ref group="2"><pubmed>1375456</pubmed></ref>. The receptor was functionally expressed in a Xenopus oocyte system. Using this sequence as a probe, we further identified and cloned additional receptor subtypes, including the EP3 subtype of the prostaglandin E2 receptor, contributing to their functional characterization<ref group="2"><pubmed>8382086</pubmed></ref><ref group="2"><pubmed>1372606</pubmed></ref><ref group="2"><pubmed>8381413</pubmed></ref>.
Prostanoids include prostaglandins and other metabolites of arachidonic acid. Based on the partial amino acid sequence of the thromboxane A2 receptor protein purified in the Narumiya laboratory at Kyoto University, we cloned the full-length cDNA from a human placental cDNA library<ref group="2"><pubmed>1825698</pubmed></ref><ref group="2"><pubmed>1375456</pubmed></ref>. The receptor was functionally expressed in a Xenopus oocyte system. Using this sequence as a probe, we further identified and cloned additional receptor subtypes, including the EP3 subtype of the prostaglandin E2 receptor, contributing to their functional characterization<ref group="2"><pubmed>8382086</pubmed></ref><ref group="2"><pubmed>1372606</pubmed></ref><ref group="2"><pubmed>8381413</pubmed></ref>.
<references group="2" />
<references group="2" />
 
=== Pharmacological Analyses of Metabotropic Glutamate Receptor ===
Metabotropic glutamate receptors (mGluRs) were first cloned in the Nakanishi laboratory, revealing a diverse family of structurally and functionally distinct receptors. Understanding the physiological roles of each subtype required subtype-specific pharmacological tools, which were not initially available. To address this, we established stable CHO cell lines expressing cloned mGluRs and performed pharmacological screening. We identified L-CCG-I and DCG-IV, both carboxycyclopropylglycine derivatives, as selective agonists for group II mGluRs<ref group="3"><pubmed>1330184</pubmed></ref><ref group="3"><pubmed>7903116</pubmed></ref>, and MCPG, a phenylglycine derivative, as an antagonist for group I and II mGluRs<ref group="3"><pubmed>8182479</pubmed></ref><ref group="3"><pubmed>8730745</pubmed></ref>.
Metabotropic glutamate receptors (mGluRs) were first cloned in the Nakanishi laboratory, revealing a diverse family of structurally and functionally distinct receptors. Understanding the physiological roles of each subtype required subtype-specific pharmacological tools, which were not initially available. To address this, we established stable CHO cell lines expressing cloned mGluRs and performed pharmacological screening. We identified L-CCG-I and DCG-IV, both carboxycyclopropylglycine derivatives, as selective agonists for group II mGluRs<ref group="3"><pubmed>1330184</pubmed></ref><ref group="3"><pubmed>7903116</pubmed></ref>, and MCPG, a phenylglycine derivative, as an antagonist for group I and II mGluRs<ref group="3"><pubmed>8182479</pubmed></ref><ref group="3"><pubmed>8730745</pubmed></ref>.


Revision as of 14:14, 12 April 2026

Here is a polished and more formal version, with **all MediaWiki code preserved exactly** and only the prose refined:

---

Yasunori Hayashi was born on July 28, 1965, in Nagoya, Aichi Prefecture, and grew up in Tokyo.

Education and Research History

  • 1984 - 1990 Kyoto University Faculty of Medicine, MD
  • 1990 - 1994 Institute for Immunology (Prof. Shigetada Nakanishi) and Department of Pharmacology (Prof. Shuh Narumiya), Kyoto University Faculty of Medicine, PhD
  • 1994 - 1996 Postdoctoral Fellow, Department of Neurophysiology (Prof. Tomoyuki Takahashi), Institute for Brain Research, Faculty of Medicine, University of Tokyo
  • 1996 - 2000 Postdoctoral Fellow, Cold Spring Harbor Laboratory (Dr. Roberto Malinow)
  • 2000 - 2009 Assistant Professor (joint), RIKEN-MIT Neuroscience Research Center, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology; Senior Scientist (joint), Brain Science Institute, RIKEN
  • 2004 - 2009 Unit Leader (joint), Brain Science Institute, RIKEN
  • 2009 - 2013 Team Leader, Brain Science Institute, RIKEN
  • 2013 - 2017 Senior Team Leader, Brain Science Institute, RIKEN
  • 2016 - Professor, Department of Pharmacology, Kyoto University Graduate School of Medicine

Past Accomplishments

Please see the project page for recent accomplishments.

Regulation of Adrenal Tyrosine Hydroxylase under Hypoxic Condition

The catecholamines dopamine, noradrenaline, and adrenaline are synthesized through a biosynthetic pathway whose rate-limiting step is catalyzed by tyrosine hydroxylase, converting tyrosine to DOPA in the presence of oxygen. In the adrenal medulla, catecholamines are released in response to stress. We therefore investigated how catecholamine synthesis is regulated under hypoxic stress[group1 1]. We found that catecholamine synthesis decreases in the brain but increases in the adrenal glands. This differential regulation likely reflects an adaptive response to increased demand under hypoxic conditions. A key question is how synthesis is maintained despite reduced oxygen availability. Our results indicate that increased affinity of tyrosine hydroxylase for its substrate, along with elevated tissue levels of tyrosine, compensates for reduced oxygen. These findings provide insight into how neurons adapt to hypoxic conditions such as cerebral ischemia.

  1. ↑ Hayashi, Y., Miwa, S., Lee, K., Koshimura, K., Hamahata, K., Hasegawa, H., ..., & Watanabe, Y. (1990).
    Enhancement of in vivo tyrosine hydroxylation in the rat adrenal gland under hypoxic conditions. Journal of neurochemistry, 54(4), 1115-21. [PubMed:1968954] [WorldCat] [DOI]

Cloning and Functional Analysis of Prostanoid Receptor

Prostanoids include prostaglandins and other metabolites of arachidonic acid. Based on the partial amino acid sequence of the thromboxane A2 receptor protein purified in the Narumiya laboratory at Kyoto University, we cloned the full-length cDNA from a human placental cDNA library[2 1][2 2]. The receptor was functionally expressed in a Xenopus oocyte system. Using this sequence as a probe, we further identified and cloned additional receptor subtypes, including the EP3 subtype of the prostaglandin E2 receptor, contributing to their functional characterization[2 3][2 4][2 5].

  1. ↑ Hirata, M., Hayashi, Y., Ushikubi, F., Yokota, Y., Kageyama, R., Nakanishi, S., & Narumiya, S. (1991).
    Cloning and expression of cDNA for a human thromboxane A2 receptor. Nature, 349(6310), 617-20. [PubMed:1825698] [WorldCat] [DOI]
  2. ↑ Namba, T., Sugimoto, Y., Hirata, M., Hayashi, Y., Honda, A., Watabe, A., ..., & Narumiya, S. (1992).
    Mouse thromboxane A2 receptor: cDNA cloning, expression and northern blot analysis. Biochemical and biophysical research communications, 184(3), 1197-203. [PubMed:1375456] [WorldCat] [DOI]
  3. ↑ Negishi, M., Sugimoto, Y., Hayashi, Y., Namba, T., Honda, A., Watabe, A., ..., & Ichikawa, A. (1993).
    Functional interaction of prostaglandin E receptor EP3 subtype with guanine nucleotide-binding proteins, showing low-affinity ligand binding. Biochimica et biophysica acta, 1175(3), 343-50. [PubMed:8382086] [WorldCat] [DOI]
  4. ↑ Sugimoto, Y., Namba, T., Honda, A., Hayashi, Y., Negishi, M., Ichikawa, A., & Narumiya, S. (1992).
    Cloning and expression of a cDNA for mouse prostaglandin E receptor EP3 subtype. The Journal of biological chemistry, 267(10), 6463-6. [PubMed:1372606] [WorldCat]
  5. ↑ Sugimoto, Y., Negishi, M., Hayashi, Y., Namba, T., Honda, A., Watabe, A., ..., & Ichikawa, A. (1993).
    Two isoforms of the EP3 receptor with different carboxyl-terminal domains. Identical ligand binding properties and different coupling properties with Gi proteins. The Journal of biological chemistry, 268(4), 2712-8. [PubMed:8381413] [WorldCat]

Pharmacological Analyses of Metabotropic Glutamate Receptor

Metabotropic glutamate receptors (mGluRs) were first cloned in the Nakanishi laboratory, revealing a diverse family of structurally and functionally distinct receptors. Understanding the physiological roles of each subtype required subtype-specific pharmacological tools, which were not initially available. To address this, we established stable CHO cell lines expressing cloned mGluRs and performed pharmacological screening. We identified L-CCG-I and DCG-IV, both carboxycyclopropylglycine derivatives, as selective agonists for group II mGluRs[3 1][3 2], and MCPG, a phenylglycine derivative, as an antagonist for group I and II mGluRs[3 3][3 4].

We then examined the role of mGluR2 in the accessory olfactory bulb. Mitral cells form reciprocal dendrodendritic synapses with granule cells, where glutamate release excites granule cells, and GABA release from granule cells inhibits mitral cells. Histological analysis revealed localization of mGluR2 on granule cells. Activation of mGluR2 by DCG-IV suppressed GABA release from granule cells, thereby reducing inhibition of mitral cells and enhancing their excitability[3 5]. This mechanism likely contributes to lateral inhibition and improves the signal-to-noise ratio in olfactory processing.

We further investigated mGluR2 function in behavior using the Bruce effect, in which female mice terminate pregnancy upon exposure to an unfamiliar male. Activation of mGluR2 in the accessory olfactory bulb by DCG-IV affected memory formation associated with this behavior[3 6]. These results suggest that mGluR2-mediated modulation of inhibitory circuits plays a key role in olfactory memory processing.

  1. ↑ Hayashi, Y., Tanabe, Y., Aramori, I., Masu, M., Shimamoto, K., Ohfune, Y., & Nakanishi, S. (1992).
    Agonist analysis of 2-(carboxycyclopropyl)glycine isomers for cloned metabotropic glutamate receptor subtypes expressed in Chinese hamster ovary cells. British journal of pharmacology, 107(2), 539-43. [PubMed:1330184] [PMC] [WorldCat] [DOI]
  2. ↑ Hayashi, Y., Momiyama, A., Takahashi, T., Ohishi, H., Ogawa-Meguro, R., Shigemoto, R., ..., & Nakanishi, S. (1993).
    Role of a metabotropic glutamate receptor in synaptic modulation in the accessory olfactory bulb. Nature, 366(6456), 687-90. [PubMed:7903116] [WorldCat] [DOI]
  3. ↑ Hayashi, Y., Sekiyama, N., Nakanishi, S., Jane, D.E., Sunter, D.C., Birse, E.F., ..., & Watkins, J.C. (1994).
    Analysis of agonist and antagonist activities of phenylglycine derivatives for different cloned metabotropic glutamate receptor subtypes. The Journal of neuroscience : the official journal of the Society for Neuroscience, 14(5 Pt 2), 3370-7. [PubMed:8182479] [PMC] [WorldCat] [DOI]
  4. ↑ Sekiyama, N., Hayashi, Y., Nakanishi, S., Jane, D.E., Tse, H.W., Birse, E.F., & Watkins, J.C. (1996).
    Structure-activity relationships of new agonists and antagonists of different metabotropic glutamate receptor subtypes. British journal of pharmacology, 117(7), 1493-503. [PubMed:8730745] [PMC] [WorldCat] [DOI]
  5. ↑ Hayashi, Y., Momiyama, A., Takahashi, T., Ohishi, H., Ogawa-Meguro, R., Shigemoto, R., ..., & Nakanishi, S. (1993).
    Role of a metabotropic glutamate receptor in synaptic modulation in the accessory olfactory bulb. Nature, 366(6456), 687-90. [PubMed:7903116] [WorldCat] [DOI]
  6. ↑ Kaba, H., Hayashi, Y., Higuchi, T., & Nakanishi, S. (1994).
    Induction of an olfactory memory by the activation of a metabotropic glutamate receptor. Science (New York, N.Y.), 265(5169), 262-4. [PubMed:8023145] [WorldCat] [DOI]

Structural Framework of Postsynaptic Density

The postsynaptic density (PSD) is an electron-dense structure located beneath excitatory synapses, yet the mechanisms underlying its structural organization have remained unclear. We found that long splice variants of Homer form tetramers via their coiled-coil domains and cross-link Shank proteins, thereby generating a mesh-like scaffold[4- 2][4- 1]. In contrast, short Homer isoforms are translated in an activity-dependent manner and function as dominant-negative regulators that disrupt this scaffold[4- 3]. This dynamic regulation provides a mechanism for homeostatic control of synaptic transmission[4- 4].

  1. Hayashi, M.K., Tang, C., Verpelli, C., Narayanan, R., Stearns, M.H., Xu, R.M., ..., & Hayashi, Y. (2009).
    The postsynaptic density proteins Homer and Shank form a polymeric network structure. Cell, 137(1), 159-71. [PubMed:19345194] [PMC] [WorldCat] [DOI]
  2. Hayashi, M.K., Ames, H.M., & Hayashi, Y. (2006).
    Tetrameric hub structure of postsynaptic scaffolding protein homer. The Journal of neuroscience : the official journal of the Society for Neuroscience, 26(33), 8492-501. [PubMed:16914674] [PMC] [WorldCat] [DOI]
  3. Sala, C., Futai, K., Yamamoto, K., Worley, P.F., Hayashi, Y., & Sheng, M. (2003).
    Inhibition of dendritic spine morphogenesis and synaptic transmission by activity-inducible protein Homer1a. The Journal of neuroscience : the official journal of the Society for Neuroscience, 23(15), 6327-37. [PubMed:12867517] [PMC] [WorldCat] [DOI]
  4. Hayashi, Y., Okamoto, K., Bosch, M., & Futai, K. (2012).
    Roles of neuronal activity-induced gene products in Hebbian and homeostatic synaptic plasticity, tagging, and capture. Advances in experimental medicine and biology, 970, 335-54. [PubMed:22351063] [WorldCat] [DOI]

Awards and Honors

  • 1998 Young Investigator Award from the Japanese Pharmacological Society
  • 2006 Departmental Teaching Award
  • 2008 JSPS Prize for Young Investigators
  • 2008 Japan Academy Medal
  • 2019 Toshihiko Tokizane Memorial Award

Societies

  • Society for Neuroscience
  • The Japan Neuroscience Society
  • The Japanese Pharmacological Society
  • The Japanese Physiological Society

Personal Aspects

Yasunori’s favorite activities include listening to music and traveling by train. His favorite composer is Johann Sebastian Bach, with a particular appreciation for organ works. He also enjoys the novels of Akira Yoshimura and essays by Masahiko Fujiwara.

Contact

Department of Pharmacology
Kyoto University Graduate School of Medicine
Room 401, Building A
Kyoto 606-8501 Japan

Tel +81-75-753-7531 x 84393
E-Mail: [yhayashi-tky@umin.ac.jp](mailto:yhayashi-tky@umin.ac.jp)

Please limit inquiries to topics related to our research and educational programs. We respectfully decline consultations regarding personal health issues.

---

If you wish, I can further tighten this into a more **award citation / CV narrative style**, which sometimes reads even more cohesively for international audiences.

Retrieved from "http://glutamate.med.kyoto-u.ac.jp/e/index.php?title=Yasunori_Hayashi&oldid=8545"