Graduate School of Medicine / School of Medicine, Faculty of Medicine

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Basic Medical Sciences

Pharmacology

The number of patients of neuropsychiatric disorders, including schizophrenia, dementia, and autism spectrum disorder is increasing rapidly in the past decades. We are addressing the machineries of the causes of such disorders. Most of these patients have problems with synaptic transmission. Synapses are the relay points for information transmitted within a complex neuronal network. Abnormal synaptic transmission is thought to be a cause of neuropsychiatric disorders. In order to understand the machinery of the cause at the molecular level, we study disease model mice with biochemical methods and super-resolved fluorescence microscopies including STED microscopy and STORM. Based on the new findings of these studies, we are planning to discover new drug targets and develop new treatments for neuropsychiatric disorders.

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  • Research & education
  • Clinical Activities
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Staffs

Professor KAWABE Hiroshi, M.D., Ph.D.
Associate Professor HANAMURA Kenji, Ph.D.
Assistant Professor YAMAZAKI Hiroyuki, Ph.D.
KOGANEZAWA Noriko, Ph.D.

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Research & Education

Research content

In our department, we study the cause of neuropsychiatric disorders at the molecular level, using the disease model mice. Especially, we are interested in post-translational modifications, including ubiquitination and phosphorylation and in rearrangement of cytoskeletons in synapses; how impairment of such biochemical reactions in synapses could cause neuropsychiatric disorders. Synapse is a structure with the size of ~200 nm, which cannot be resolved by a standard fluorescence microscopy with the resolution of 250 nm. We also study the ultrastructure of synapses using super resolution microscopies, such as N-STORM and STED microscopy, which have resolutions of 20-30 nm, in order to understand the cause of neuropsychiatric disorders.

Business education

(School of Medicine)
Pharmacology (lecture and training) and Neuroscience (lecture), Medical and Scientific Writing (training), Writing of Tutorial Medical Paper (training), Basic Medicine Training.

(Graduate School of Medicine)
Pharmacology (lecture, seminar and technical course), In vitro neural monitoring training course (lecture and training), Technical Course for Live Imaging (lecture and training), Basic and clinical neuroscience lecture series (lecture), Drug Discovery and education of research (two graduate students)

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Clinical Activities

(no clinical assignments)

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Citizenship Activities

We have helped the organization of Brain Awareness Week since 2000 and Gunma prefectural Chuo secondary school. In addition, we helped the foundation of KITA-KANTO BIO-FORUM to contribute to society.

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Achievements

List of Publication by Prof. KAWABE Hiroshi

Ambrozkiewicz MC*, Borisova E, Schwark M, Ripamonti S, Schaub T, Smorodchenko A, Weber AI, Rhee HJ, Altas B, Yilmaz R, Mueller S, Piepkorn L, Horan ST, Straussberg R, Zaqout S, Jahn O, Dere E, Rosário M, Boehm-Sturm P, Borck G, Willig K, Rhee JS, Tarabykin V, Kawabe H.* (2020) The murine ortholog of Kaufman oculocerebrofacial syndrome protein Ube3b regulates synapse number by ubiquitinating Ppp3cc. Molecular Psychiatry accepted. *=Corresponding authors

Hoshino S, Kobayashi M, Tagawa R, Konno R, Abe T, Furuya K, Miura K, Wakasawa H, Okita N, Sudo Y, Mizunoe Y, Nakagawa Y, Nakamura T, Kawabe H, Higami Y. (2020) WWP1 knockout mice have exacerbated obesity-related phenotype in white adipose tissue but improved whole body glucose metabolism. FEBS Open Bio 10:306-315.

Luo L, Ambrozkiewicz MC, Benseler F, Chen C, Dumontier E, Falkner S, Furlanis E, Gomez AM, Hoshina N, Huang WH, M Hutchison MA, Itoh-Maruoka Y, Lavery LA, Li W, Maruo T, Motohashi J, Pai ELL, Pelkey KA, Pereira A, Philips T, Sinclair JL, Stogsdill JA, Traunmüller L, Wang J, Wortel J, You W, Abumaria N, Beier KT, Brose N, Burgess HA, Cepko CL, Cloutier JF, Eroglu C, Goebbels S, Kaeser PS, Kay JN, Lu W, Luo L, Mandai K, McBain CJ, Nave KA, Prado MAM, Prado VF, Rothstein J, Rubenstein JLR, Saher G, Sakimura K, Sanes JR, Scheiffele P, Takai Y, Umemori H, Verhage M, Yuzaki M, Zoghbi HY, Kawabe H*, Craig AM*. (2020) Optimizing nervous system-specific gene targeting with Cre driver lines: prevalence of germline recombination and influencing factors. Neuron 106:1–29. *=Corresponding authors

Ambrozkiewicz MC*, Schwark M, Kishimoto-Suga M, Borisova E, Hori K, Salazar-Lázaro A, Rusanova A, Altas B, Piepkorn L, Bessa P, Schaub T, Zhang X, Rabe T, Ripamonti S, Rosário M, Akiyama H, Jahn O, Kobayashi T, Hoshino M, Tarabykin V, Kawabe H*. (2018) Polarity acquisition in cortical neurons is driven by synergistic action of Sox9-regulated Wwp1 and Wwp2 E3 ubiquitin ligases and intronic miR-140. Neuron 100:1097-1115. *=Corresponding authors

Ogawa M, Matsuda R, Tomokiyo M, Takada N, Yamamoto S, Shizukusihi S, Yamaji T, Yoshikawa Y, Yoshida M, Tanida I, Koike M, Murai M, Morita H, Takeyama H, Ryo A, Guan JL, Yamamoto M, Inoue JI, Yanagawa T, Fukuda M, Kawabe H, Ohnishi M. (2018) Molecular mechanisms of Streptococcus pneumoniae-targeted autophagy via pneumolysin, Golgi-resident Rab41, and Nedd4-1 mediated K63-linked ubiquitination. Cellular Microbiology 20:e12846.

Bhouri M, Morishita W, Temkin P, Goswami D, Kawabe H, Brose N, Südhof TC, Craig AM, Siddiqui TJ, Malenka R. (2018) Deletion of LRRTM1 and LRRTM2 in adult mice impairs basal AMPA receptor transmission and LTP in hippocampal CA1 pyramidal neurons. Proc. Natl. Acad. Sci. USA. 115:E5382-E5389.

Pei G, Buijze H, Liu H, Moura-Alves P, Goosmann C, Brinkmann V, Kawabe H, Dorhoi A, Kaufmann SHE. (2017) The E3 ubiquitin ligase NEDD4 enhances killing of membrane-perturbing intracellular bacteria by promoting autophagy. Autophagy 13:2041-2055.

Henshall TL, Manning JA, Alfassy OS, Boase NA, Goel P, Kawabe H, Kumar S. (2017) Deletion of Nedd4-2 results in progressive kidney disease in mice. Cell Death Differ. 24:2150-2160.

Lee JH, Jeon SA, Kim BG, Takeda M, Cho JJ, Kim DI, Kawabe H, Cho JY. (2017) Nedd4 deficiency in vascular smooth muscle promotes vascular calcification by stabilizing pSmad1. J. Bone Miner. Res. 32:927-938.

Crosby JR, Zhao C, Jiang C, Bai D, Katz M, Greenlee S, Kawabe H, McCaleb M, Rotin D, Guo S, Monia BP. (2017) Inhaled ENaC antisense oligonucleotide ameliorates cystic fibrosis-like lung disease in mice. J. Cyst. Fibros. 16:671-680.

Zhou Z, Kawabe H, Suzuki A, Shinmyozu K, Saga Y. (2017) NEDD4 controls spermatogonial stem cell homeostasis and stress response by regulating messenger ribonucleoprotein complexes. Nat. Commun. 8:15662.

Sigler A, Oh WC, Imig C, Altas B, Kawabe H, Cooper BH, Kwon HB, Rhee JS, Brose N. (2017) Formation and maintenance of functional spines in the absence of presynaptic glutamate release. Neuron 94:304-311.

Kawabe H, Mitkovski M, Kaeser PS, Hirrlinger J, Opazo F, Nestvogel D, Kalla S, Fejtova A, Verrier SE, Bungers SR, Cooper BH, Varoqueaux F, Wang Y, Nehring RB, Gundelfinger ED, Rosenmund C, Rizzoli SO, Südhof TC, Rhee JS, Brose N. (2017) ELKS1 localizes the synaptic vesicle priming protein bMunc13-2 to a specific subset of active zones. J. Cell Biol. 216:143-161.

Jiang C, Kawabe H, Rotin D. (2017) The ubiquitin ligase Nedd4L regulates the Na/K/2Cl co-transporter NKCC1/SLC12A2 in the colon. J. Biol. Chem. 292:137-145.

Ripamonti S, Ambrozkiewicz MC, Guzzi F, Gravati M, Biella G, Bormuth I, Hammer M, Tuffy LP, Sigler A, Kawabe H, Nishimori K, Toselli M, Brose N, Parenti M, Rhee JS. (2017) Transient oxytocin signaling primes the development and function of excitatory hippocampal neurons. elife 6:22466.

Lu C, Thoeni C, Connor A, Kawabe H, Gallinger S, Rotin D. (2016) Intestinal knockout of Nedd4 enhances growth of Apcmin tumors. Oncogene 35: 5839- 5849.

Canal M, Martín-Flores N, Pérez-Sisqués L, Romaní-Aumedes J, Altas B, Man HY, Kawabe H, Alberch J, Malagelada C. (2016) Loss of NEDD4 contributes to RTP801 elevation and neuron toxicity:implications for Parkinson’s disease. Oncotarget 7:58813-58831.

Lipina TV, Prasad T, Yokomaku D, Luo L, Connor SA, Kawabe H, Wang YT, Brose N, Roder JC, Craig AM. (2016) Cognitive deficits in Calsyntenin-2-deficient mice associated with reduced GABAergic transmission. Neuropsychopharmacology 41:802-810.

Ott C, Martens H, Hassouna I, Oliveira B, Erck C, Zafeiriou MP, Peteri UK, Hesse D, Gerhart S, Altas B, Kolbow T, Stadler H, Kawabe H, Zimmermann WH, Nave KA, Schulz-Schaeffer W, Jahn O, Ehrenreich H. (2015) Widespread expression of erythropoietin receptor in brain and its induction by injury. Mol. Med. 21:803-815.

Hsia HE, Kumar R, Luca R, Takeda M, Courchet J, Nakashima J, Wu S, Goebbels S, An W, Eickholt B, Polleux F, Rotin D, Wu H, Rossner M, Bagni C, Rhee JS, Brose N, Kawabe H*. (2014) Ubiquitin E3 ligase Nedd4-1 acts as a downstream target of PI3K/PTEN-mTORC1 signaling to promote neurite growth. Proc. Natl. Acad. Sci. USA. 111:13205-13210. *=Corresponding author

Pettem KL, Yokomaku D, Luo L, Linhoff MW, Prasad T, Connor SA, Siddiqui TJ, Kawabe H, Chen F, Zhang L, Rudenko G, Wang YT, Brose N, Craig AM. (2013) The specific α-Neurexin interactor Calsyntenin-3 promotes excitatory and inhibitory synapse development. Neuron 80:113-128.

Siddiqui TJ, Tari PK, Conner SA, Zhang P, Dobie FA, She K, Kawabe H, Wang YT, Brose N, Craig AM. (2013) An LRRTM4-HSPG complex mediates excitatory synapse development on dentate gyrus granule cells. Neuron 79:680-695.

Nagpal P, Plant PJ, Correa J, Bain A, Takeda M, Kawabe H, Rotin D, Bain JR, Batt JA. (2012) The ubiquitin ligase Nedd4-1 participates in denervation-induced skeletal muscle atrophy in mice. PLOS One 7:e46427.

Cooper B, Hemmerlein M, Ammermüller J, Imig C, Reim K, Lipstein N, Kalla S, Kawabe H, Brose N, Brandstätter JH, Varoqueaux F. (2012) Munc13-independent vesicle priming at mouse photoreceptor ribbon synapses. J. Neurosci. 32:8040-8052.

Kimura T*, Kawabe H*, Jiang C, Zhang W, Xiang YY, Lu C, Salter MW, Brose N, Lu WY, Rotin D. (2011) Deletion of the ubiquitin ligase Nedd4L in lung epithelia causes cystic fibrosis-like disease. Proc. Natl. Acad. Sci. USA. 108:3216-3221. *=Equal contribution

Kawabe H*, Neeb A, Dimova K, Young SM Jr, Takeda M, Katsurabayashi S, Mitkovski M, Malakhova OA, Zhang DE, Umikawa M, Kariya K, Goebbels S, Nave KA, Rosenmund C, Jahn O, Rhee JS, Brose N*. (2010) Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development. Neuron 65:358-372. *=Corresponding authors

Fouladkou F, Lu C, Jiang C, Zhou L, She Y, Walls JR, Kawabe H, Brose N, Henkelman RM, Huang A, Bruneau BG, Rotin D. (2010) The ubiquitin ligase NEDD4-1 is required for heart development and is a suppressor of thrombospondin-1. J. Biol. Chem. 285:6770-6780.

Gómez-Varela D, Kohl T, Schmidt M, Rubio ME, Kawabe H, Nehring RB, Schäfer S, Stühmer W, Pardo LA. (2010) Characterization of Eag1 channel lateral mobility in rat hippocampal cultures by single-particle-tracking with quantum dots. PLOS One 5:e8858.

Trimbuch T, Beed P, Vogt J, Schuchmann S, Maier N, Kintscher M, Breustedt J, Schuelke M, Streu N, Kieselmann O, Brunk I, Laube G, Strauss U, Battefeld A, Wende H, Birchmeier C, Wiese S, Sendtner M, Kawabe H, Kishimoto-Suga M, Brose N, Baumgart J, Geist B, Aoki J, Savaskan NE, Bräuer AU, Chun J, Ninnemann O, Schmitz D, Nitsch R. (2009) Synaptic PRG-1 modulates excitatory transmission via lipid phosphate-mediated signaling. Cell 138:1222-1235.

Fouladkou F, Landry T, Kawabe H, Neeb A, Lu C, Brose N, Stambolic V, Rotin D. (2008) The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization. Proc. Natl. Acad. Sci. USA. 105:8585-8590.

Dimova K*, Kawabe H*, Betz A, Brose N, Jahn O. (2006) Characterization of the Munc13-calmodulin interaction by photoaffinity labeling. Biochim. Biophys. Acta Mol. Cell Res. 1763:1256-1265. *=Equal contribution

Andrews-Zwilling YS, Kawabe H, Reim K, Varoqueaux F, Brose N. (2006) Binding to Rab3A-interacting molecule RIM regulates the presynaptic recruitment of Munc13-1 and ubMunc13-2. J. Biol. Chem. 281:19720-19731.

Kawabe H, Sakisaka T, Yasumi M, Shingai T, Izumi G, Nagano F, Deguchi-Tawarada M, Takeuchi M, Nakanishi H, Takai Y. (2003) A novel rabconnectin-3-binding protein that directly binds a GDP/GTP exchange protein for Rab3A small G protein implicated in Ca2+-dependent exocytosis of neurotransmitter. Genes Cells 8:537-546.

Nagano F*, Kawabe H*, Nakanishi H, Shinohara M, Deguchi-Tawarada M, Takeuchi M, Sasaki T, Takai Y. (2002) Rabconnectin-3, a novel protein that binds both GDP/GTP exchange protein and GTPase-activating protein for Rab3 small G protein family. J. Biol. Chem. 277:629-632. *=Equal contribution

Kawabe H, Nakanishi H, Asada M, Fukuhara A, Morimoto K, Takeuchi M, Takai Y. (2001) Pilt, a novel peripheral membrane protein at tight junctions in epithelial cells. J. Biol. Chem. 276:48350-48355.

Deguchi M, Iizuka T, Hata Y, Nishimura W, Hirao K, Yao I, Kawabe H, Takai Y. (2000) PAPIN. A novel multiple PSD-95/Dlg-A/ZO-1 protein interacting with neural plakophilin-related armadillo repeat protein/delta-catenin and p0071. J. Biol. Chem. 275:29875-29880.

Kikyo M, Matozaki T, Kodama A, Kawabe H, Nakanishi H, Takai Y. (2000) Cell-cell adhesion-mediated tyrosine phosphorylation of nectin-2delta, an immunoglobulin-like cell adhesion molecule at adherens junctions. Oncogene 19:4022-4028.

Yao I, Ohtsuka T, Kawabe H, Matsuura Y, Takai Y, Hata Y. (2000) Association of membrane-associated guanylate kinase-interacting protein-1 with Raf-1. Biochem. Biophys. Res. Commun. 270:538-542.

Hirao K, Hata Y, Deguchi M, Yao I, Ogura M, Rokukawa C, Kawabe H, Mizoguchi A, Takai Y. (2000) Association of synapse-associated protein 90/ postsynaptic density-95-associated protein (SAPAP) with neurofilaments. Genes Cells 5:203-210.

Hirao K, Hata Y, Yao I, Deguchi M, Kawabe H, Mizoguchi A, Takai Y. (2000) Three isoforms of synaptic scaffolding molecule and their characterization: multimerization between the isoforms and their interaction with N-methyl-D-aspartate receptors and SAP90/PSD-95-associated protein. J. Biol. Chem. 275:2966-2972.

Kawabe H, Hata Y, Takeuchi M, Ide N, Mizoguchi A, Takai Y. (1999) nArgBP2, a novel neural member of ponsin/ArgBP2/vinexin family that interacts with synapse-associated protein 90/postsynaptic density-95-associated protein (SAPAP). J. Biol. Chem. 274:30914-30918.

Shimizu K, Kawabe H, Minami S, Honda T, Takaishi K, Shirataki H, Takai Y. (1996) SMAP, an Smg GDS-associating protein having arm repeats and phosphorylated by Src tyrosine kinase. J. Biol. Chem. 271:27013-27017.

List of Publication by old Pharmacology

Yin XL, Jia QF, Zhang GY, Zhang JP, Shirao T, Jiang CX, Yin XY, Liu YS, Chen P, Gu XC, Qian ZK, Yin GZ, Sen Xia H, Hui L. (2019) Association between decreased serum TBIL concentration and immediate memory impairment in schizophrenia patients. Sci. Rep. 9:1622.

Miki D, Kobayashi Y, Okada T, Miyamoto T, Takei N, Sekino Y, Koganezawa N, Shirao T, Saito Y. (2019) Characterization of functional primary cilia in human induced pluripotent stem cell-derived neurons. Neurochem. Res. 44:1736-1744.

Mitsuoka T, Hanamura K, Koganezawa N, Kikura-Hanajiri R, Sekino Y, Shirao T. (2019) Assessment of NMDA receptor inhibition of phencyclidine analogues using a high-throughput drebrin immunocytochemical assay. J. Pharmacol. Toxicol. Methods. 106583

Hanamura K, Koganezawa N, Kamiyama K, Tanaka N, Oka T, Yamamura M, Sekino Y, Shirao T. (2019) High-content imaging analysis for detecting the loss of drebrin clusters along dendrites in cultured hippocampal neurons. J. Pharmacol. Toxicol. Methods. 106607.

Puspitasari A, Yamazaki H, Kawamura H, Nakano T, Takahashi A, Shirao T, Held KD. (2019) X-irradiation of developing hippocampal neurons causes changes in neuron population phenotypes, dendritic morphology and synaptic protein expression in surviving neurons at maturity. Neurosci. Res. S0168-0102: 30320-7.

Miao S, Koganezawa N, Hanamura K, Puspitasari A, Shirao T. (2018) N-methyl-D-aspartate receptor mediates X-irradiation-induced drebrin decrease in hippocampus. Kitakanto Medical Journal 68: 111-115

Hanamura K, Kamata Y, Yamazaki H, Kojima N, Shirao T. (2018) Isoform-dependent regulation of drebrin dynamics in dendritic spines. Neuroscience 379: 67–76

Yamazaki H, Sasagawa Y, Yamamoto H, Bito H, Shirao T. (2018) CaMKIIβ is localized in dendritic spines as both drebrin-dependent and drebrin-independent pools. J. Neurochem. 146:145-159.

Yasuda H, Kojima N, Yamazaki H, Hanamura K, Sakimura K, Shirao T. (2018) Drebrin isoforms critically regulate NMDAR- and mGluR-dependent LTD induction. Front. Cell. Neurosci. 12:330.

小金澤紀子、花村健次、白尾智明 (2017) 「ヒトiPS細胞由来神経細胞を用いた医薬品評価系の現状について」日本薬理学雑誌 149: 104-109

Shirao T, Hanamura K, Koganezawa N, Ishizuka Y, Yamazaki H, Sekino Y. (2017) The role of drebrin in neurons. J. Neurochem. 141:819-834.

Koganezawa N, Hanamura K, Sekino Y, Shirao T. (2017) The role of drebrin in dendritic spines. Mol. Cell. Neurosci. 84:85-92.

Li B, Ding S, Feng N, Mooney N, Ooi YS, Renf L, Diep J, Kelly MR, Yasukawa LL, Patton JT, Yamazaki H, Shirao T, Jackson PK, Greenberg HB. (2017) Drebrin restricts rotavirus entry by inhibiting dynamin-mediated endocytosis. Proc. Natl. Acad. Sci. USA. 114:E3642-E3651.

Kajita Y, Kojima N, Koganezawa N, Yamazaki H, Sakimura K, Shirao T. (2017) Drebrin E regulates neuroblast proliferation and chain migration in the adult brain. Eur. J. Neurosci. 46:2214-2228.

Hanamura K, Washburn HR, Sheffler-Collins SI, Xia NL, Henderson N, Tillu DV, Hassler S, Spellman DS, Zhang G, Neubert TA, Price TJ, Dalva MB. (2017) Extracellular phosphorylation of a receptor tyrosine kinase controls synaptic localization of NMDA receptors and regulates pathological pain. PLoS Biol. 15:e2002457.

Shirao T, Sekino Y. (Eds.) (2017) Drebrin. (Advances in Experimental Medicine and Biology, vol 1006) Tokyo, Springer

Sekino Y, Koganezawa N, Mizui T, Shirao T. (2017) Role of Drebrin in Synaptic Plasticity. Adv. Exp. Med. Biol. 1006:183-201.

Yamazaki H, Shirao T. (2017) Homer, Spikar, and Other Drebrin-Binding Proteins in the Brain. Adv. Exp. Med. Biol. 1006:249-268.

Shirao T, Koganezawa N, Yamazaki H, Hanamura K, Imamura K. (2017) Localization of Drebrin: Light Microscopy Study. Adv. Exp. Med. Biol. 1006:105-118.

Shirao T, Sekino Y. (2017) General Introduction to Drebrin. Adv. Exp. Med. Biol. 1006:3-22.

Ishizuka Y, Hanamura K. (2017) Drebrin in Alzheimer’s Disease. Adv. Exp. Med. Biol. 1006:203-223.

Hanamura K. (2017) Drebrin in Neuronal Migration and Axonal Growth. Adv. Exp. Med. Biol. 1006:141-155.

Puspitasari A, Koganezawa N, Ishizuka Y, Kojima N, Tanaka N, Nakano T, Shirao T. (2016) X Irradiation Induces Acute Cognitive Decline via Transient Synaptic

Dysfunction. Radiat. Res. 185:423-30.

Fujieda T, Koganezawa N, Ide Y, Shirao T, Sekino Y. (2015) An Inhibitory Pathway Controlling the Gating Mechanism of the Mouse Lateral Amygdala Revealed by Voltage-Sensitive Dye Imaging. Neuroscience Letters 590:126-131.

Xu S, Buraschi S, Morcavallo A, Genua M, Shirao T, Peiper SC, Gomella LG, Birbe R, Belfiore A, Iozzo RV, Morrione A. (2015) A novel role for drebrin in regulating progranulin bioactivity in urothelial cancer. Oncotarget 6:10825-39.

Ishizuka Y, Shimizu H, Takagi E, Kato M, Yamagata H, Mikuni M, Shirao T. (2014) Histone deacetylase mediates the decrease in drebrin cluster density induced by amyloid beta oligomers. Neurochem. Int. 76:114-121.

Tanabe K, Yamazaki H, Inaguma Y, Asada A, Kimura T, Takahashi J, Taoka M, Ohshima T, Furuichi T, Isobe T, Nagata K, Shirao T, Hisanaga S. (2014) Phosphorylation of drebrin by cyclin-dependent kinase 5 and its role in neuronal migration. PLOS One 9:e92291.

Ishikawa M, Shiota J, Ishibashi1 Y, Hakamata T, Shoji S, Fukuchi M, Masaaki Tsuda M, Shirao T, Sekino Y, Baraban JM, Tabuchi A. (2014) Cellular localization and dendritic function of rat isoforms of the SRF coactivator MKL1 in cortical neurons. NeuroReport 25:585-592.

Mizui T,Sekino Y, Yamazaki H, Ishizuka Y, Takahashi H, Kojima N, Kojima M, Shirao T. (2014) Myosin Ⅱ ATPase activity mediates the long-term potentiation-induced exodus of stable F-actin bound by drebrin A from dendritic spines. PLOS One 9: e85367.

Yamazaki H, Kojima N, Kato K, Hirose H, Iwasaki T, Mizui T, Takahashi H, Hanamura K, Roppongi RT, Koibuchi N, Sekino Y, Mori N, Shirao T. (2013) Spikar, a novel drebrin-binding protein, regulates the formation and stabilization of dendritic spines. J. Neurochem. 128:507-522.

白尾智明、山崎博幸 (2013)「樹状突起棘(スパイン)のアクチンフィラメントと微小管」 Clinical Neuroscience 31: 1302-1395.

Ishikawa M, Shiota J, Ishibashi Y, Hakamata T, Shoji S, Fukuchi M, Tsuda M, Shirao T, Sekino Y, Ohtsuka T, Baraban JM, Tabuchi A. (2013) Identification, expression and characterization of rat isoforms of the SRF coactivator MKL1. FEBS Open Bio. 3:387-393.

Ishizuka Y, Kakiya N, Witters LA, Oshiro N, Shirao T, Nawa H, Takei N. (2013) AMP-activated protein kinase (AMPK) counteractsbrain-derived neurotrophic factor (BDNF)-induced mammalian target of rapamycin complex 1 (mTORC1) signaling in neurons. J. Neurochem. 127:66-77.

Shirao T, Gonzalez-Billault C. (2013) Actin filaments and microtubules in dendritic spines. J. Neurochem. 126:155-164.

Roppongi RT, Kojima N, Hanamura K, Yamazaki H, Shirao T. (2013) Selective reduction of drebrin and actin in dendritic spines of hippocampal neurons by activation of 5-HT2A receptors. Neurosci. Lett. 547:76-81.

Shirai K, Mizui T, Suzuki Y, Okamoto M, Hanamura K, Yoshida Y, Hino M, Noda S, AL-Jahdari WS, Chakravarti A, Shirao T, Nakano T. (2012) X-Irradiation Changes Dendritic Spine Morphology and Density through Reduction of Cytoskeletal Proteins in Mature Neurons. Radiation Research 179:630-636.

Canto CB, Koganezawa N, Beed P, Moser EI, Witter MP. (2012) All layers of medial entorhinal cortex receive presubicular and parasubicular inputs. J. Neurosci. 32: 17620-17631.

Kato K, Shirao T, Yamazaki H, Imamura K, Sekino Y. (2012) Regulation of AMPA receptor recruitment by the actin binding protein drebrin in cultured hippocampal neurons. J. Neurosci. Neuroeng. 1: 153-160.

Tanaka K, Sato K, Yoshida T, Fukuda T, Hanamura K, Kojima N, Shirao T, Yanagawa T, and Watanabe H. (2011) Evidence for cell density affecting C2C12 myogenesis: possible regulation of myogenesis by cell-cell communication. Muscle and Nerve 44:968-977.

Kobayashi-Yamazaki C, Shirao T, Sasagawa Y, Maruyama Y, Akita H, Saji M, Sekino Y. (2011) Lesions of the supramammillary nucleus decrease self-grooming behavior of rats placed in an open field The Kitakanto Medical Jorunal 61:287-292.

Han W, Takamatsu Y, Yamamoto H, Kasai S, Endo S, Shirao T, Kojima N, Ikeda K. (2011) Inhibitory role of inducible cAMP early repressor (ICER) in methamphetamine-induced locomotor sensitization. PLOS One 6:e21637.

Okamoto T, Endo S, Shirao T, Nagao S. (2011) Role of Cerebellar Cortical Protein Synthesis in Transfer of Memory Trace of Cerebellum-Dependent Motor Learning. J. Neurosci. 31:8958-66.

Kambe T, Motoi Y, Inoue R, Kojima N, Tada N, Kimura T, Sahara N, Yamashita S, Mizoroki T, Takashima A, Shimada K, Ishiguro K, Mizuma H, Onoe H, Mizuno Y, Hattori N. (2011) Differential regional distribution of phosphorylated tau and synapse loss in the nucleus accumbens in tauopathy model mice. Neurobiol. Dis. 42:404-414.

Kaminuma T, Suzuki Y, Shirai K, Mizui T, Noda S, Yosida Y, Funayama T, Takahasi T, Kobayashi Y, Shirao T, Nakano T. (2010) Effectiveness of carbon-ion beams for apoptosis induction in rat primary immature hippocampal neurons. J. Rad. Res. 51:627-631.

Hanamura K, Mizui T, Kakizaki T, Roppongi TR, Yamazaki H, Yanagawa Y, Shirao T (2010) Low accumulation of drebrin at glutamatergic postsynaptic sites on GABAergic neurons. Neuroscience 169:1489-1500.

Perez-Martinez M, Gordon-Alonso M, Cabrero JR, Barrero-Villar M, Rey M, Mittelbrunn M, Lamana A, Morlino G, Calabia C, Yamazaki H, Shirao T, Vazquez J, Gonzalez-Amaro R, Veiga E, Sanchez-Madrid F. (2010) F-actin-binding protein drebrin regulates CXCR4 recruitment to the immune synapse. J. Cell Sci. 123:1160-1170.

Mercer JC, Mottram LF Qi Q, Lee YC, Bruce D, Iyer A, Yamazaki H, Shirao T, Choe MH, Peterson BR, August A. (2010) Chemico-Genetic Identification of Drebrin as a Regulator of Calcium Responses. Int. J. Biochem. Cell Biol. 42:337-345.

Kojima N, Hanamura K, Yamazaki H, Ikeda T, Itohara S, Shirao T. (2010) Genetic disruption of the alternative splicing of drebrin gene impairs context-dependent fear learning in adulthood. Neuroscience 165: 138-150.

Okamoto M, Suzuki Y, Shirai K, Mizui T, Yoshida Y, Noda S, Al-Jahdari WS, Shirao T, Nakano T. (2009) Effect of Irradiation on the Development of Immature Hippocampal Neurons In Vitro. Radiat. Res. 172:718-724.

Aoki C, Kojima N, Sabaliauskas N, Shah L, Oakford J, Ahmed T, Yamazaki H, Hanamura K, Shirao T. (2009) Drebrin A Knock-Out Eliminates the Rapid Form of Homeostatic Synaptic Plasticity at Excitatory Synapses of Intact Adult Cerebral Cortex. J. Comp. Neurol. 517:105-121.

Ito M, Shirao T, Doya K, Sekino Y. (2009) Three-dimensional distribution of Fos-positive neurons in the supramammillary nucleus of the rat exposed to novel environment. Neurosci. Res. 64:397-402.

Mizui T, Kojima N, Yamazaki H, Katayama M, Hanamura K, Shirao T. (2009) Drebrin E is involved in the mechanism regulating axonal growth through actin-myosin interactions. J. Neurochem. 109:611-622.

Takahashi T, Yamazaki H, Hanamura K, Sekino Y, Shirao T. (2009) AMPA receptor inhibition causes abnormal dendritic spines by destabilizing drebrin. J. Cell. Sci. 122:1211-1229.

Ivanov A, Esclapez M, Pellegrino1 C, Shirao T, Ferhat L. (2009) Drebrin A regulates the dendritic spine plasticity and synaptic function in cultured hippocampal neurons. J. Cell. Sci. 122: 524-534.

Kojima N, Borlikova G, Sakamoto T, Yamada K, Ikeda T, Itohara S, Niki H, Endo S. (2008) Inducible cAMP early repressor acts as a negative regulator for kindling epileptogenesis and long-term fear memory. J. Neurosci. 28:6459-6472.

Song M, Kojima N, Hanamura K, Sekino Y, Inoue KH, Mikuni M, Shirao T. (2008) Expression of drebrin E in migrating neuroblasts in adult rat brain: coincidence between drebrin E disappearance from cell body and cessation of migration. Neuroscience 152:670-682.

Kobayashi C, Aoki C, Kojima N, Yamazaki H, Shirao T. (2007) Drebrin A content correlates with spine head size in the adult mouse cerebral cortex. J. Comp. Neurol. 503:618-26.

Sekino Y, Kojima N, Shirao T. (2007) Role of actin cytoskeleton in dendritic spine morphogenesis. Neurochem. Int. 51:92-104.

Kato K, Sekino Y, Takahashi H, Yasuda H, Shirao T. (2007) Increase of AMPA receptors-mediated miniature EPSC amplitude after chronic NMDA receptor blockade in cultured hippocampal neurons. Neurosci. Lett. 418: 4-8.

Kojima N, Shirao T. (2007) Synaptic dysfunction and disruption of the postsynaptic drebrin-actin complex: the study of neurological disorders accompanied by cognitive deficits. Neurosci. Res. 58: 1-5.

Majoul I, Shirao T, Sekino Y, Duden R. (2007) Many faces of Drebrin: from building dendritic spines and stabilizing gap junctions to shaping neurite-like cell processes. Histochem. Cell. Biol. 127: 355-361.

Shirai K, Mizui T, Suzuki Y, Kobayashi Y, Nakano T, Shirao T. (2006) Differential effects of x-irradiation on immature and mature hippocampal neurons in vitro. Neurosci. Lett. 399: 57-60.

Chang EH, Savage MJ, Flood DG, Thomas JM, Levy RB, Mahadomrongkul V, Shirao T, Aoki C, Huerta PT. (2006) AMPA receptor downscaling at the onset of Alzheimer’s pathology in double knock-in mice. Proc. Natl. Acad. Sci. USA. 103: 3410-3415.

Fujisawa S, Shirao T, Aoki C. (2006) In vivo, competitive blockade of NMDA receptors induces rapid shape change of post-synaptic spines and F-actin reorganization within dendritic spines of adult rat cortex. Neuroscience 140:1177-1187.

Takahashi H, Mizui T, Shirao T. (2006) Downregulation of drebrin A expression suppresses synaptic targeting of NMDA receptors in developing hippocampal neurons. J. Neuochem. 97(s1):110-115.

Sekino Y, Tanaka S, Hanamura K, Yamazaki H, Sasagawa Y, Xue Y, Hayashi K, Shirao T. (2006) Activation of N-methyl-D-aspartate receptor induces a shift of drebrin distribution: disappearance from dendritic spines and appearance in dendritic shafts. Mol. Cell. Neurosci. 31: 493-504.

Mahadomrongkul V, Huerta PT, Shirao T, Aoki C. (2005) Stability of the distribution of spines containing drebrin A in the sensory cortex layer I of mice expressing mutated APP and PS1 genes. Brain Res. 1064: 66-74.

Mizui T, Takahashi H, Sekino Y, Shirao T. (2005) Overexpression of drebrin A in immature neurons induces the accumulation of F-actin and PSD-95 into dendritic filopodia, and the formation of large abnormal protrusions. Mol. Cell. Neurosci. 30: 149-157.

Aoki C, Sekino Y, Hanamura K, Fujisawa S, Mahadomrongkul V, Ren Y, Shirao T. (2005) Drebrin A is a Postsynaptic Protein that Localizes in vivo to the Submembranous Surface of Dendritic Sites Forming Excitatory Synapses. J. Comp. Neurol. 483:383-402.

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History

1993
SHIRAO Tomoaki started his research at Gunma University as a professor.

1997
YAMAZAKI Hiroyuki joined as a graduate student.

2003
HANAMURA Kenji joined as a research associate.

2012
KOGANEZAWA Noriko joined as an assistant professor.

2018
HANAMURA Kenji was promoted to an associate professor..

2020
SHIRAO Tomoaki retired.

2020
KAWABE Hiroshi started his research as a professor.