メンバー紹介/スタッフ

助教:坂口 怜子-Reiko Sakaguchi

助教:坂口 怜子
生物の細胞の中では、外界からの刺激に応じてイオンや有機小分子など様々なシグナル伝達物質が産生され、これらの物質の「濃度の変化」を「情報」として伝えています。細胞内シグナル伝達のメカニズムは複雑で、破綻した場合疾患の原因にもなりますが、まだまだ不明な点が多く残されています。そこで私は、生きた単一細胞内における各シグナル伝達物質の濃度挙動を検出する蛍光性プローブを開発し、これらのプローブを使って、細胞が情報を伝える仕組みを明らかにすることを目指しています。また、光応答性の多孔性配位高分子(Porous Coordination Polymer, PCP)を使って、細胞が気体性シグナル分子に曝された場合の細胞応答の観察も行っています。

rsakaguchi@icems.kyoto-u.ac.jp

学歴

平成15年3月 京都大学 総合人間学部 自然環境学科 卒業
平成17年3月 京都大学大学院エネルギー科学研究科 エネルギー基礎科学専攻修士課程 修了
平成20年3月 京都大学大学院エネルギー科学研究科 エネルギー基礎科学専攻博士後期課程 研究指導認定退学

職歴

平成20年4月〜平成21年11月 京都大学エネルギー理工学研究所 研修員
平成20年4月〜平成21年9月 京都大学高等教育研究開発推進機構 非常勤講師
平成21年12月〜平成25年6月 Thomas Jefferson University 博士研究員
平成25年7月〜2020年3月 京都大学物質−細胞統合システム拠点(iCeMS)特定拠点助教
2020年4月~ 京都大学大学院 工学研究科 合成・生物化学専攻 助教

賞罰等

2014年10月 Outstanding Presentation Award for Young Scientists. The 87th Annual Meeting of the Japanese Biochemical Society, Kyoto, Japan.
2011年6月 Outstanding Presenter Award. 6th Annual Postdoctral Research Symposium, Pennsylvania, U.S.A.
2010年6月 Outstanding Presenter Award. 5th Annual Postdoctral Research Symposium, Pennsylvania, U.S.A.
2007年9月 Young Scientists Poster Award. 2nd International workshop on approaches to single-cell analysis, Tokyo, Japan.
2005年12月 Pacifichem 2005 Student Poster Competition. 2005 International Chemical Congress of Pacific Basin Societies, Hawaii, U.S.A.

研究業績リスト/原著論文

23
Tachizaki T, Sakaguchi R, Terada S, Kamei K, Hirori H.
Terahertz pulse-altered gene networks in human induced pluripotent stem cells.
Optics Letters, 45, 6078-6081 2020.
22
Uchiyama M, Nakao A, Kurita Y, Fukushi I, Takeda K, Numata T, Tran HN, Sawamura S, Ebert M, Kurokawa T, Sakaguchi R, Stokes A, Takahashi N, Okada Y, Mori Y.
O2-Dependent Protein Internalization Underlies Astrocytic Sensing of Acute Hypoxia by Restricting Multimodal TRPA1 Channel Responses.
Curr Biol. 30, 3378-3396 2020.
21
Tajima S, Nakata E, Sakaguchi R, Saimura M, Mori Y, Morii T.
Fluorescence detection of the nitric oxide-induced structural change at the putative nitric oxide sensing segment of TRPC5.
Bioorg Med Chem. 28, 115430 2020.
20
Masamune A, Kotani H, Sörgel FL, Chen JM, Hamada S, Sakaguchi R, Masson E, Nakano E, Kakuta Y,
Niihori T, Funayama R, Shirota M, Hirano T, Kawamoto T, Hosokoshi A, Kume K, Unger L, Ewers M,
Laumen H, Bugert P, Mori MX, Tsvilovskyy V, Weißgerber P, Kriebs U, Fecher-Trost C, Freichel M,
Diakopoulos KN, Berninger A, Lesina M, Ishii K, Itoi T, Ikeura T, Okazaki K, Kaune T, Rosendahl J,
Nagasaki M, Uezono Y, Algül H, Nakayama K, Matsubara Y, Aoki Y, Férec C, Mori Y, Witt H,
Shimosegawa T.
Variants that Affect Function of Calcium Channel TRPV6 are Associated with Early-onset Chronic Pancreatitis.
Gastroenterology. pii: S0016-5085(20) 30017-2 2020.
19
Polat OK, Uno M, Maruyama T, Tran HN, Imamura K, Wong CF, Sakaguchi R, Ariyoshi M, Itsuki K,
Ichikawa J, Morii T, Shirakawa M, Inoue R, Asanuma K, Reiser J, Tochio H, Mori Y, Mori MX.
Contribution of Coiled-Coil Assembly to Ca2+/Calmodulin-Dependent Inactivation of TRPC6 Channel and its Impacts on FSGS-Associated Phenotypes.
J Am Soc Nephrol. 30, 1587-1603 2019.
18
Qian N, Ichimura A, Takei D, Sakaguchi R, Kitani A, Nagaoka R, Tomizawa M, Miyazaki Y,
Miyachi H, Numata T, Kakizawa S, Nishi M, Mori Y, Takeshima H.
TRPM7 channels mediate spontaneous Ca2+ fluctuations in growth plate chondrocytes that promote bone development.
Sci Signal. 12, eaaw4847 2019.
17
Masuda I, Igarashi T, Sakaguchi R, Nitharwal RG, Takase R, Han KY, Leslie BJ, Liu C, Gamper H,
Ha T, Sanyal S, Hou YM.
A genetically encoded fluorescent tRNA is active in live-cell protein synthesis.
Nucleic Acids Res. 45, 4081-4093, 2017.
16
T. Christian‡, R. Sakaguchi‡, AP Perlinska‡, G. Lahoud, T. Ito, EA Taylor, S. Yokoyama,
JI Sulkowska, and *YM Hou.
Methyl transfer by substrate signaling from a knotted protein fold.
Nat. Struct. Mol. Biol. 10, 941-948, 2016 ‡: equal contribution.
15
Badr H, Kozai D, Sakaguchi R, Numata T, Mori Y.
Different Contribution of Redox-Sensitive Transient Receptor Potential Channels to Acetaminophen-Induced Death of Human Hepatoma Cell Line.
Front Pharmacol. 7, 19, 2016.
14
Shigeki Kiyonaka, Reiko Sakaguchi,Itaru Hamachi, Takashi Morii, Takenao Yoshizaki and Yasuo Mori.
Validating subcellular thermal changes revealed by fluorescent thermosensors.
Nat. Methods. 12, 801-802, 2015.
13
Laurie Griffin, Reiko Sakaguchi, David McGuigan, Michael A. Gonzalez, Charles Searby, Stephan Züchner, Ya-Ming Hou and Anthony Antonellis.
Impaired Function is a Common Feature of Neuropathy-Associated Glycyl-tRNA Synthetase Mutations.
Human Mutation. 35, 1363-71, 2014.
12
Reiko Sakaguchi, Georges Lahoud, Thomas Christian, Howard Gamper, Ya-Ming Hou.
A Divalent Metal Ion-Dependent N1-Methyl Transfer to G37-tRNA.
Chemistry & Biology. 21, 1351–60, 2014.
11
James Pham, Reiko Sakaguchi, Lee Yeoh, Nilushi De Silva, Geoffrey McFadden, Ya Ming Hou and Stuart Ralph.
A dual-targeted aminoacyl-tRNA synthetase in Plasmodium falciparum charges cytosolic and apicoplast tRNACys.
Biochem J. 458, 513-23, 2014.
10
Shigeki Kiyonaka, Taketoshi Kajimoto, Reiko Sakaguchi, Daisuke Shinmi, Mariko Omatsu-Kanbe, Hiroshi Matsuura, Hiromi Imamura, Takenao Yoshizaki, Itaru Hamachi, Takashi Morii, and Yasuo Mori.
Genetically encoded fluorescent thermo-sensors for visualizing subcellular thermoregulation in living cells.
Nature Methods. 10, 1232-38, 2013.
9
Isao Masuda, Reiko Sakaguchi, Cuiping Liu, Howard Gamper and Ya-Ming Hou.
The temperature sensitivity of a mutation in the essential tRNA modification enzyme tRNA methyltransferase D (TrmD).
J Biol Chem. 288, 28987-96, 2013.
8
Anna Ochi, Koki Makabe, Ryota Yamagami, Akira Hirata, Reiko Sakaguchi, Ya-Ming Hou, Kazunori Watanabe, Osamu Nureki, Kunihiro Kuwajima and Hiroyuki Hori.
The Catalytic Domain of Topological Knot tRNA Methyltransferase (TrmH) Discriminates between Substrate tRNA and Nonsubstrate tRNA via an Induced-fit Process.
J Biol Chem. 288, 25562-74, 2013.
7
Shun Nakano, Masatora Fukuda, Tomoki Tamura, Reiko Sakaguchi, Eiji Nakata, and Takashi Morii.
Simultaneous Detection of ATP and GTP by Covalently Linked Fluorescent Ribonucleopeptide Sensors.
J Am Chem Soc. 135, 3465-73, 2013.
6
Reiko Sakaguchi, Anders Giessing, Qing Dai, Georges Lahoud, Zita Liutkeviciute, Saulius Klimasauskas, Joseph Piccirilli, Finn Kirpekar and Ya-Ming Hou.
Recognition of guanosine by dissimilar tRNA methyltransferases.
RNA. 18, 1687-1701, 2012.
5
Heather McLaughlin, Reiko Sakaguchi, William Giblin, NIH Intramural Sequencing Center, Thomas Wilson, Leslie Biesecker, James Lupski, Kevin Talbot, Jeffery Vance, Stephan Züchner, Yi-Chung Lee, Marina Kennerson, Ya-Ming Hou, Garth Nicholson, Anthony Antonellis.
A recurrent loss-of-function alanyl-tRNA synthetase (AARS) mutation in patients with charcot-marie-tooth disease type 2N (CMT2N).
Human Mutation. 33, 244-253, 2012.
4
Amit Ghosh, Reiko Sakaguchi, Cuiping Liu, Saraswathi Vishveshwara and Ya-Ming Hou.
Allosteric communication in cysteinyl tRNA synthetase: a network of direct and indirect readout.
J Biol Chem. 286, 37721-31, 2011.
3
Heather McLaughlin, Reiko Sakaguchi, Cuiping Liu, Takao Igarashi, Davut Pehlivan, Kristine Chu, Ram Iyer, Pedro Cruz, Praveen Cherukuri, Nancy Hansen, James Mullikin, NISC Comparative Sequencing Program, Leslie Biesecker, Thomas Wilson, Victor Ionasescu, Garth Nicholson, Charles Searby, Kevin Talbot, Jeffrey Vance, Stephan Züchner, Kinga Szigeti, James Lupski, Ya-Ming Hou, Eric Green and Anthony Antonellis.
Compound heterozygosity for loss-of-function lysyl-tRNA synthetase mutations in a patient with peripheral neuropathy.
Am. J. Hum. Genet. 87, 560-566, 2010.
2
Reiko Sakaguchi, Kazuki Tainaka, Naoko Shimada, Shun Nakano, Masafumi Inoue, Shigeki Kiyonaka, Yasuo Mori, and Takashi Morii.
An in vivo fluorescent sensor reveals intracellular Ins(1,3,4,5)P4 dynamics in single cells.
Angew. Chem. Int. Ed. 49, 2150-2153, 2010.
1
Reiko Sakaguchi, Takashi Endoh, Seigo Yamamoto, Kazuki Tainaka, Kenji Sugimoto, Nobutaka Fujieda, Shigeki Kiyonaka, Yasuo Mori, and Takashi Morii.
A single circularly permuted GFP sensor for inositol-1,3,4,5-tetrakisphosphate based on a split PH domain.
Bioorg. Med. Chem. 17, 7381-7386, 2009.

研究業績リスト/総説および著書(英文)

7
Sakaguchi R, Tajima S, Mori Y, Morii T.
Detection of Inositol Phosphates by Split PH Domains.
Methods Mol Biol. 2091, 47-57 2020.
6
Sakaguchi R, Mori Y.
Transient receptor potential (TRP) channels: Biosensors for redox environmental stimuli and cellular status.
Free Radic Biol Med. 146, 47-57 2019.
5
Okabe K, Sakaguchi R, Shi B, Kiyonaka S.
Intracellular thermometry with fluorescent sensors for thermal biology.
Pflugers Archiv : European journal of physiology. 470, 717-731 2018.
4
Daisuke Kozai, Reiko Sakaguchi, Tomohiko Ohwada and Yasuo Mori.
Deciphering Subtype-Selective Modulations in TRPA1 Biosensor Channels.
Current Neuropharmacology. 13, 266-278, 2015.
3
Reiko Sakaguchi, Shigeki Kiyonaka, Yasuo Mori.
Fluorescent sensors reveal subcellular thermal changes.
Curr Opin Biotechnol. 31C, 57-64, 2014.
2
Kazuki Tainaka, Reiko Sakaguchi, Hironori Hayashi, Shun Nakano, Fong-Fong Liew, and Takashi Morii
Design strategies of fluorescent biosensors based on biological macromolecular receptors.
Sensors. 10, 1355-1376, 2010.
1
Kenji Sugimoto, Reiko Sakaguchi, Yasuo Mori, and Takashi Morii.
Recent advances in biosensing second messengers.
Recent Res. Devel. Chem. 2, 73-89, 2004.

研究業績リスト/総説および著書(和文)

6
坂口 怜子
細胞内温度センサーの種類と特徴
実験医学 38, 1491-1494, 2020.
5
坂口 怜子
細胞の中で起こっていることを見てみよう
化学と教育 65, 126-127, 2017.
4
坂口 怜子, Ya-Ming Hou
タンパク質の結び目構造からのシグナルによるtRNAのメチル化修飾
ライフサイエンス 新着論文レビュー: First Author's DOI: 10.7875/first.author.2016.097
3
清中 茂樹, 坂口 怜子
蛍光タンパク質サーモセンサーによる細胞内温度変化の可視化
生体の科学 66, 169-174, 2015
2
坂口 怜子, 清中 茂樹, 森 泰生
細胞内熱産生機構の可視化
医学のあゆみ 252, 256 -257, 2015
1
清中 茂樹, 坂口 怜子, 森 泰生
蛍光性センサータンパク質による細胞内温度分布の可視化
生物物理 54, 253-256, 2014