The Biosafety Administration Division manages radiation sources, infectious materials, and other hazardous materials used in NCGG. We maintain radioisotope facilities and BSL2 and BSL3 laboratories so that research using these materials is conducted smoothly. We also provide education and training for researchers to carry out experiments safely and securely in compliance with applicable laws and regulations.
NCGG has two radiation safety-controlled areas on 1st and 5th floors of the Research Building 1.
This area consists of chemical laboratories, a cell culture room, a radioactivity measurement room, a cold room, a dark room, and an animal facility. With various instruments including a scintillation counter and an X-ray irradiator, investigators can conduct a wide range of molecular analysis using radiolabeled substances.
This area is designed to conduct bioimaging analysis with radioactive probes. We have a cyclotron for labeled probe production and a PET scanner for experimental animals. Isolators are installed in the animal room, enabling long-term repetitive observations.
In BSL2 laboratories, investigators can conduct infection experiments with pathogens such as viruses and bacteria and gene transfer using viral vectors. It is also possible to conduct animal infection experiments in ABSL2 and ABS3 laboratories in the animal facility.
| Associate Professor | Akihiko Nishikimi |
|---|---|
| Research Fellow | Ryohei Kondo |
| Research Assistant | Junko Hirokawa |
| Research Assistant | Yuko Tottori |
| Radiological Technician | Yasuo Imai |
| Visiting Scientist | Akira Nakanishi |
| Visiting Researcher | Mitsuihiro Fujiwara |
Infection of microorganisms such as viruses and bacteria causes many diseases. Our body is protected against infection by the immune system, which detects and eliminates these pathogens. The immune system can memorize previously encountered pathogens, making it possible to respond more rapidly and effectively on a secondary infection. Vaccination provides immunological memory by injecting agents that resemble pathogens and produces protective immunity against infection.
Immunological memory is provided by memory cells, activated antigen specific B cells and T cells persist after the elimination of pathogens. With aging the lymphocyte pool is occupied by memory cells by exposure to antigen as well as reduction of the new lymphocyte supply. This makes vaccination to aged individuals less effective, especially those against new pathogens.
Because our immune system responds specifically against pathogens and infected cells, damage of normal tissue is limited. Upon aging, non-specific immune response increases whereas effector function of immune cells declines. Persistence of low-grade and non-specific immune response results in chronic inflammation, which causes various age-related diseases.
In our laboratory, we are studying the mechanism of age-related dysfunction and dysregulation of the immune system, particularly focusing on immunological memory and senescence of immune cells. Our goal is to develop methods to restore immune competence and prolong normal immune functions for healthy aging.
Block J, Rashkova C, Castanon I, Zoghi S, Platon J, Ardy RC, Fujiwara M, Chaves B, Schoppmeyer R, van der Made CI, Jimenez Heredia R, Harms FL, Alavi S, Alsina L, Sanchez Moreno P, Ávila Polo R, Cabrera-Pérez R, Kostel Bal S, Pfajfer L, Ransmayr B, Mautner AK, Kondo R, Tinnacher A, Caldera M, Schuster M, Domínguez Conde C, Platzer R, Salzer E, Boyer T, Brunner HG, Nooitgedagt-Frons JE, Iglesias E, Deyà-Martinez A, Camacho-Lovillo M, Menche J, Bock C, Huppa JB, Pickl WF, Distel M, Yoder JA, Traver D, Engelhardt KR, Linden T, Kager L, Hannich JT, Hoischen A, Hambleton S, Illsinger S, Da Costa L, Kutsche K, Chavoshzadeh Z, van Buul JD, Antón J, Calzada-Hernández J, Neth O, Viaud J, Nishikimi A, Dupré L, Boztug K. Systemic inflammation and normocytic anemia in DOCK11 deficiency. N Engl J Med (2023) doi: 10.1056/NEJMoa2210054.
Sugiyama Y, Harada T, Kamei Y, Yasuda T, Mashimo T, Nishikimi A*, Maruyama M* (*corresponding authors). A senolytic immunotoxin eliminates p16INK4a-positive T cells and ameliorates age-associated phenotypes of CD4+ T cells in a surface marker knock-in mouse. Exp Gerontol (2023) 174:112130.
Nishikimi A, Nakagawa T, Fujiwara M, Watanabe K, Watanabe A, Komatsu A, Yasuoka M, Watanabe R, Naya M, Oshima H, Kitagawa Y, Tokuda H, Kondo I, Niida S, Sakurai T, Kojima M, Arai H. Humoral and cellular responses to the third COVID-19 BNT162b2 vaccine dose in research institute workers in Japan. J Infect (2023) 86: e33-e35.
Yamamoto S, Tanaka A, Ohmagari N, Yamaguchi K, Ishituka K, Morisaki N, Kojima M, Nishikimi A, Tokuda H, Inoue M, Tanaka S, Umezawa J, Okubo R, Nishimura K, Konishi M, Miyo K, Mizoue T. Use of heated tobacco products, moderate alcohol drinking, and anti-SARS-CoV-2 IgG antibody titers after BNT162b2 vaccination among Japanese healthcare workers. Prev Med (2022) 161: 107123.
Nishikimi A, Watanabe K, Watanabe A, Yasuoka M, Watanabe R, Fujiwara M, Oshima H, Nakagawa T, Kitagawa Y, Tokuda H, Washimi Y, Niida S, Kojima M. Immune responses to COVID-19 vaccine BNT162b2 in workers at a research institute in Japan: 6-month follow-up survey. J Infect (2022) 85: 174-176.
Sugiyama Y, Fujiwara M, Sakamoto A, Tsushima H, Nishikimi A, Maruyama M. The immunosenescence-related factor DOCK11 is involved in secondary immune responses of B cells. Immun Aging (2022) 19: 2.
Nishikimi A, Watanabe K, Watanabe A, Yasuoka M, Watanabe R, Oshima H, Kitagawa Y, Tokuda H, Niida S, Kojima M. Prevalence of SARS-CoV-2 antibodies after one-year follow up among workers in a research institute in Japan. J Infect (2021) 84: e23-e25.
Nishikimi A, Kojima M, Watanabe K, Watanabe A, Yasuoka M, Oshima H, Tokuda H, Niida S. Seroprevalence of antibodies against SARS-CoV-2 among workers in a national research institute and hospital in Central Japan. GHM Open (2021) 1: 40-42.
Okumura F, Fujiki Y, Oki N, Osaki K, Nishikimi A, Fukui Y, Nakatsukasa K, Kamura T. Cul5-type ubiquitin ligase KLHDC1 contributes to the elimination of truncated SELENOS produced by failed UGA/Sec decoding. iScience. (2020) 3: 100970.
Momoi Y, Nishikimi A, Du G, Kataoka T, Katagiri K. Phosphatidic acid regulates subcellular distribution of RA-GEFs critical for chemokine-dependent migration. Biochem Biophys Res Commun. (2020) 524: 325-331.
Ushijima M, Uruno T, Nishikimi A, Sanematsu F, Kamikaseda Y, Kunimura K, Sakata D, Okada T, Fukui Y. The Rac Activator DOCK2 Mediates Plasma Cell Differentiation and IgG Antibody Production. Front Immunol. (2018) 9: 243.
Nishikimi A, Koyama YI, Ishihara S, Kobayashi S, Tometsuka C, Kusubata M, Kuwaba K, Hayashida O, Hattori S, Katagiri K. Collagen-derived peptides modulate CD4+ T-cell differentiation and suppress allergic responses in mice. Immun Inflamm Dis. (2018) 6: 245-255.
Okumura F, Joo-Okumura A, Obara K, Petersen A, Nishikimi A, Fukui Y, Nakatsukasa K, Kamura T.
Ubiquitin ligase SPSB4 diminishes cell repulsive responses mediated by EphB2. Mol Biol Cell. (2017) 28: 3532-3541.
Uematsu K, Okumura F, Tonogai S, Joo-Okumura A, Alemayehu DH, Nishikimi A, Fukui Y, Nakatsukasa K, Kamura T. ASB7 regulates spindle dynamics and genome integrity by targeting DDA3 for proteasomal degradation. J Cell Biol. (2016) 215: 95-106.
Okumura F, Uematsu K, Byrne SD, Hirano M, Joo-Okumura A, Nishikimi A, Shuin T, Fukui Y, Nakatsukasa K, Kamura T. Parallel Regulation of von Hippel-Lindau Disease by pVHL-Mediated Degradation of B-Myb and Hypoxia-Inducible Factor α. Mol Cell Biol. (2016) 36: 1803-1817.
Ishihara S, Nishikimi A, Umemoto E, Miyasaka M, Saegusa M, Katagiri K. Dual functions of Rap1 are crucial for T-cell homeostasis and prevention of spontaneous colitis. Nat Commun. (2015) 6: 8982.
Watanabe M, Terasawa M, Miyano K, Yanagihara T, Uruno T, Sanematsu F, Nishikimi A, Côté JF, Sumimoto H, Fukui Y. DOCK2 and DOCK5 act additively in neutrophils to regulate chemotaxis, superoxide production, and extracellular trap formation. J Immunol. (2014) 193: 5660-5667.
Nishikimi A, Ishihara S, Ozawa M, Etoh K, Fukuda M, Kinashi T, Katagiri K. Rab13 acts downstream of the kinase Mst1 to deliver the integrin LFA-1 to the cell surface for lymphocyte trafficking. Sci Signal. (2014) 7: ra72.
Ogawa K, Tanaka Y, Uruno T, Duan X, Harada Y, Sanematsu F, Yamamura K, Terasawa M, Nishikimi A, Côté JF, Fukui Y. DOCK5 functions as a key signaling adaptor that links FcεRI signals to microtubule dynamics during mast cell degranulation. J Exp Med. (2014) 11: 1156-1156.
Nishikimi A, Kukimoto-Niino M, Yokoyama S, Fukui Y. Immune regulatory functions of DOCK family proteins in health and disease. Exp Cell Res. (2013) 319: 2343-2349.
Kamakura S, Nomura M, Hayase J, Iwakiri Y, Nishikimi A, Takayanagi R, Fukui Y, Sumimoto H. The cell polarity protein mInsc regulates neutrophil chemotaxis via a noncanonical G protein signaling pathway. Dev Cell. (2013) 26: 292-302.
Sakai Y, Tanaka Y, Yanagihara T, Watanabe M, Duan X, Terasawa M, Nishikimi A, Sanematsu F, Fukui Y. The Rac activator DOCK2 regulates natural killer cell-mediated cytotoxicity in mice through the lytic synapse formation. Blood. (2013) 22: 386-393.
Sanematsu F, Nishikimi A, Watanabe M, Hongu T, Tanaka Y, Kanaho Y, Côté JF, Fukui Y. Phosphatidic acid-dependent recruitment and function of the Rac activator DOCK1 during dorsal ruffle formation. J Biol Chem. (2013) 288: 8092-8100.
Fujimori S, Hirai N, Ohashi H, Masuoka K, Nishikimi A, Fukui Y, Washio T, Oshikubo T, Yamashita T, Miyamoto-Sato E. Next-generation sequencing coupled with a cell-free display technology for high-throughput production of reliable interactome data. Sci Rep. (2012) 2: 691.
Terasawa M, Uruno T, Mori S, Kukimoto-Niino M, Nishikimi A, Sanematsu F, Tanaka Y, Yokoyama S, Fukui Y. Dimerization of DOCK2 is essential for DOCK2-mediated Rac activation and lymphocyte migration. PLoS One. (2012) 7: e46277.
Nishikimi A, Uruno T, Duan X, Cao Q, Okamura Y, Saitoh T, Saito N, Sakaoka S, Du Y, Suenaga A, Kukimoto-Niino M, Miyano K, Gotoh K, Okabe T, Sanematsu F, Tanaka Y, Sumimoto H, Honma T, Yokoyama S, Nagano T, Kohda D, Kanai M, Fukui Y. Blockade of inflammatory responses by a small-molecule inhibitor of the Rac activator DOCK2. Chem Biol. (2012) 19: 488-497.
Harada Y, Tanaka Y, Terasawa M, Pieczyk M, Habiro K, Katakai T, Hanawa-Suetsugu K, Kukimoto-Niino M, Nishizaki T, Shirouzu M, Duan X, Uruno T, Nishikimi A, Sanematsu F, Yokoyama S, Stein JV, Kinashi T, Fukui Y. DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration during immune responses. Blood. (2012) 119: 4451-61.
Hanawa-Suetsugu K, Kukimoto-Niino M, Mishima-Tsumagari C, Akasaka R, Ohsawa N, Sekine S, Ito T, Tochio N, Koshiba S, Kigawa T, Terada T, Shirouzu M, Nishikimi A, Uruno T, Katakai T, Kinashi T, Kohda D, Fukui Y, Yokoyama S. Structural basis for mutual relief of the Rac guanine nucleotide exchange factor DOCK2 and its partner ELMO1 from their autoinhibited forms. Proc Natl Acad Sci U S A. (2012) 109: 3305-3310.
Sanematsu F, Hirashima M, Laurin M, Takii R, Nishikimi A, Kitajima K, Ding G, Noda M, Murata Y, Tanaka Y, Masuko S, Suda T, Meno C, Côté JF, Nagasawa T, Fukui Y. DOCK180 is a Rac activator that regulates cardiovascular development by acting downstream of CXCR4. Circ Res. (2010) 107: 1102-1105.
Gotoh K, Tanaka Y, Nishikimi A, Nakamura R, Yamada H, Maeda N, Ishikawa T, Hoshino K, Uruno T, Cao Q, Higashi S, Kawaguchi Y, Enjoji M, Takayanagi R, Kaisho T, Yoshikai Y, Fukui Y. Selective control of type I IFN induction by the Rac activator DOCK2 during TLR-mediated plasmacytoid dendritic cell activation. J Exp Med. (2010) 207: 721-730.
Nishikimi A, Fukuhara H, Su W, Hongu T, Takasuga S, Mihara H, Cao Q, Sanematsu F, Kanai M, Hasegawa H, Tanaka Y, Shibasaki M, Kanaho Y, Sasaki T, Frohman MA, Fukui Y. Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis. Science. (2009) 324: 384-387.
Gotoh K, Tanaka Y, Nishikimi A, Inayoshi A, Enjoji M, Takayanagi R, Sasazuki T, Fukui Y. Differential requirement for DOCK2 in migration of plasmacytoid dendritic cells versus myeloid dendritic cells. Blood. (2008) 111: 2973-2976.
Tanaka Y, Hamano S, Gotoh K, Murata Y, Kunisaki Y, Nishikimi A, Takii R, Kawaguchi M, Inayoshi A, Masuko S, Himeno K, Sasazuki T, Fukui Y. T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-alpha subunit controlled by the Rac activator Dock2.
Nat Immunol. (2007) 8: 1067-1075.
Kunisaki Y, Nishikimi A, Tanaka Y, Takii R, Noda M, Inayoshi A, Watanabe K, Sanematsu F, Sasazuki T, Sasaki T, Fukui Y. DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis. J Cell Biol. (2006) 174: 647-652.
Chen W, Nishikimi A, Kamata T, Adachi Y. A reducing and denaturing step maximizes the immunoprecipitations of m-calpain and I-2(PP2A)/SET: an approach toward antibodies that do not work well in immunoprecipitation. J Biochem Biophys Methods. (2006) 68: 65-68.
Uekawa N, Terauchi K, Nishikimi A, Shimada J, Maruyama M. Expression of TARSH gene in MEFs senescence and its potential implication in human lung cancer. Biochem Biophys Res Commun. (2005) 329: 1031-1038.
Nishikimi A, Meller N, Uekawa N, Isobe K, Schwartz MA, Maruyama M. Zizimin2: a novel, DOCK180-related Cdc42 guanine nucleotide exchange factor expressed predominantly in lymphocytes. FEBS Lett. (2005) 579: 1039-1046.
Akihiko Nishikimi
Phone: +81-562-46-2311 (ext. 5058, 5244)
e-mail: a-nishikimi(at)ncgg.go.jp
Biosafety Administration
National Center for Geriatrics and Gerontology
7-430 Morioka-cho, Obu, Japan
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