研究業績

2023

53: Miyagi T and Kanekura K. Intricate roles of spacers and stickers of Arg-rich C9ORF72 dipeptide repeat proteins: from toxicity to targeting to membraneless organelles. Organelle, 2023. accepted.

52: Miyagi T, Ueda K, Sugimoto M, Yagi T, Ito D, Yamazaki R, Narumi S, Hayamizu Y, Uji-i H, Kuroda M, Kanekura K. Differential toxicity and localization of arginine-rich C9ORF72 dipeptide repeat proteins depend on de-clustering of positive charges. iScience 2023 May 25;26(6):106957. doi: 10.1016/j.isci.2023.106957.

2022

51: Miyagi T, Yamazaki R, Ueda K, Narumi S, Hayamizu Y, Uji-I H, Kuroda M, Kanekura K. The Patterning and Proportion of Charged Residues in the Arginine- Rich Mixed-Charge Domain Determine the Membrane-Less Organelle Targeted by the Protein. Int J Mol Sci. 2022 Jul 11;23(14):7658. doi: 10.3390/ijms23147658. PMID: 35887012; PMCID: PMC9324279.

50: Chen C, Jia H, Nakamura Y, Kanekura K, Hayamizu Y. Effect of Multivalency on Phase-Separated Droplets Consisting of Poly(PR) Dipeptide Repeats and RNA at the Solid/Liquid Interface. ACS Omega. 2022 Jun 3;7(23):19280-19287. doi: 10.1021/acsomega.2c00811. PMID: 35721931; PMCID: PMC9201888.

49: Kanekura K, Yamanaka Y, Miyagi T, Kuroda M. Chemically oligomerizable TDP-43: a novel chemogenetic tool for studying the pathophysiology of amyotrophic lateral sclerosis. Neural Regen Res. 2022 Nov;17(11):2434-2436. doi: 10.4103/1673-5374.335803. PMID: 35535888; PMCID: PMC9120673.

48: Chen C, Jia H, Nakamura Y, Kanekura K, Hayamizu Y. Effect of Multivalency on Phase-Separated Droplets Consisting of Poly(PR) Dipeptide Repeats and RNA at the Solid/Liquid Interface. ACS Omega. 2022 Jun 3;7(23):19280-19287. doi: 10.1021/acsomega.2c00811. PMID: 35721931; PMCID: PMC9201888.

47: Kanekura K, Kuroda M. How can we interpret the relationship between liquid- liquid phase separation and amyotrophic lateral sclerosis? Lab Invest. 2022 Sep;102(9):912-918. doi: 10.1038/s41374-022-00791-x. Epub 2022 Apr 22. PMID: 35459796.

46: Ohno SI, Oikawa K, Tsurui T, Harada Y, Ono K, Tateishi M, Mirza A, Takanashi M, Kanekura K, Nagase K, Shimada Y, Kudo Y, Ikeda N, Ochiya T, Wang X, Kuroda M. Nuclear microRNAs release paused Pol II via the DDX21-CDK9 complex. Cell Rep. 2022 Apr 12;39(2):110673. doi: 10.1016/j.celrep.2022.110673. PMID: 35417682.

45: Kanekura K, Hayamizu Y, Kuroda M. Order controls disordered droplets: structure-function relationships in C9ORF72-derived poly(PR). Am J Physiol Cell Physiol. 2022 Feb 1;322(2):C197-C204. doi: 10.1152/ajpcell.00372.2021. Epub 2021 Dec 15. PMID: 34910602.

2021

44: Jigjidkhorloo N, Kanekura K, Matsubayashi J, Akahane D, Fujita K, Oikawa K, Kurata A, Takanashi M, Endou H, Nagao T, Gotoh A, Norov O, Kuroda M. Expression of L-type amino acid transporter 1 is a poor prognostic factor for Non-Hodgkin's lymphoma. Sci Rep. 2021 Nov 4;11(1):21638. doi: 10.1038/s41598-021-00811-8. PMID: 34737339; PMCID: PMC8569019.

43: Miyagi T, Yamanaka Y, Harada Y, Narumi S, Hayamizu Y, Kuroda M, Kanekura K. An improved macromolecular crowding sensor CRONOS for detection of crowding changes in membrane-less organelles under stressed conditions. Biochem Biophys Res Commun. 2021 Oct 27;583:29-34. doi: 10.1016/j.bbrc.2021.10.055. Epub ahead of print. PMID: 34717122.

42: Chen C, Yamanaka Y, Ueda K, Li P, Miyagi T, Harada Y, Tezuka S, Narumi S, Sugimoto M, Kuroda M, Hayamizu Y, Kanekura K. Phase separation and toxicity of C9orf72 poly(PR) depends on alternate distribution of arginine. J Cell Biol. 2021 Nov 1;220(11):e202103160. doi: 10.1083/jcb.202103160. Epub 2021 Sep 9. PMID: 34499080; PMCID: PMC8438627.

41: Yamanaka Y, Miyagi T, Harada Y, Kuroda M, Kanekura K. Establishment of chemically oligomerizable TAR DNA-binding protein-43 which mimics amyotrophic lateral sclerosis pathology in mammalian cells. Lab Invest. 2021 Oct;101(10):1331-1340. doi: 10.1038/s41374-021-00623-4. Epub 2021 Jun 15. PMID: 34131277.

40: Chen C, Li P, Luo W, Nakamura Y, Dimo VS, Kanekura K, Hayamizu Y. Diffusion of LLPS Droplets Consisting of Poly(PR) Dipeptide Repeats and RNA on Chemically Modified Glass Surface. Langmuir. 2021 May 11;37(18):5635-5641. doi: 10.1021/acs.langmuir.1c00493. Epub 2021 Apr 30. PMID: 33929866.

39: Umezu T, Takanashi M, Murakami Y, Ohno SI, Kanekura K, Sudo K, Nagamine K, Takeuchi S, Ochiya T, Kuroda M. Acerola exosome-like nanovesicles to systemically deliver nucleic acid medicine via oral administration. Mol Ther Methods Clin Dev. 2021 Mar 10;21:199-208. doi: 10.1016/j.omtm.2021.03.006. PMID: 33850951; PMCID: PMC8010214.

2020

38: Umezu T, Tsuneyama K, Kanekura K, Hayakawa M, Tanahashi T, Kawano M, Taguchi YH, Toyoda H, Tamori A, Kuroda M, Murakami Y. Comprehensive analysis of liver and blood miRNA in precancerous conditions. Sci Rep. 2020 Dec 10;10(1):21766. doi: 10.1038/s41598-020-78500-1. PMID: 33303811; PMCID: PMC7728755.

37: Yagi T, Asada R, Kanekura K, Eesmaa A, Lindahl M, Saarma M, Urano F. Neuroplastin Modulates Anti-inflammatory Effects of MANF. iScience. 2020 Nov 17;23(12):101810. doi: 10.1016/j.isci.2020.101810. PMID: 33299977; PMCID: PMC7702011.

36: Yakou F, Suwanai H, Ishikawa T, Itou M, Shikuma J, Miwa T, Sakai H, Kanekura K, Narumi S, Suzuki R, Odawara M. A Novel Homozygous Mutation of Thyroid Peroxidase Gene Abolishes a Disulfide Bond Leading to Congenital Hypothyroidism. Int J Endocrinol. 2020 Aug 30;2020:9132372. doi: 10.1155/2020/9132372. PMID: 32908504; PMCID: PMC7477596.

35: Yamaguchi T, Higa K, Yagi-Yaguchi Y, Ueda K, Noma H, Shibata S, Nagai T, Tomida D, Yasu-Mimura R, Ibrahim O, Matoba R, Tsubota K, Hamrah P, Yamada J, Kanekura K, Shimazaki J. Pathological processes in aqueous humor due to iris atrophy predispose to early corneal graft failure in humans and mice. Sci Adv. 2020 May 13;6(20):eaaz5195. doi: 10.1126/sciadv.aaz5195. PMID: 32426498; PMCID: PMC7220341.

34: Mahadevan J, Morikawa S, Yagi T, Abreu D, Lu S, Kanekura K, Brown CM, Urano F. A soluble endoplasmic reticulum factor as regenerative therapy for Wolfram syndrome. Lab Invest. 2020 Sep;100(9):1197-1207. doi: 10.1038/s41374-020-0436-1. Epub 2020 May 4. PMID: 32366942; PMCID: PMC7438202.

33: Ueda S, Takanashi M, Sudo K, Kanekura K, Kuroda M. miR-27a ameliorates chemoresistance of breast cancer cells by disruption of reactive oxygen species homeostasis and impairment of autophagy. Lab Invest. 2020 Jun;100(6):863-873. doi: 10.1038/s41374-020-0409-4. Epub 2020 Feb 17. PMID: 32066826.

32: Hiraide T, Kataoka M, Suzuki H, Aimi Y, Chiba T, Isobe S, Katsumata Y, Goto S, Kanekura K, Yamada Y, Moriyama H, Kitakata H, Endo J, Yuasa S, Arai Y, Hirose N, Satoh T, Hakamata Y, Sano M, Gamou S, Kosaki K, Fukuda K. Poor outcomes in carriers of the RNF213 variant (p.Arg4810Lys) with pulmonary arterial hypertension. J Heart Lung Transplant. 2020 Feb;39(2):103-112. doi: 10.1016/j.healun.2019.08.022. Epub 2019 Sep 2. PMID: 31542298.

2019

31: Ueda A, Oikawa K, Fujita K, Ishikawa A, Sato E, Ishikawa T, Kuroda M, Kanekura K. Therapeutic potential of PLK1 inhibition in triple-negative breast cancer. Lab Invest. 2019 Sep;99(9):1275-1286. doi: 10.1038/s41374-019-0247-4. Epub 2019 Apr 17. PMID: 30996295.

2018

30:Suzuki H, Kataoka M, Hiraide T, Aimi Y, Yamada Y, Katsumata Y, Chiba T, Kanekura K, Isobe S, Sato Y, Satoh T, Gamou S, Fukuda K, Kosaki K. Genomic Comparison With Supercentenarians Identifies RNF213 as a Risk Gene for Pulmonary Arterial Hypertension. Circ Genom Precis Med. 2018 Dec;11(12):e002317. doi: 10.1161/CIRCGEN.118.002317. PMID: 30562119.

29: Kanekura K, Harada Y, Fujimoto M, Yagi T, Hayamizu Y, Nagaoka K, Kuroda M. Characterization of membrane penetration and cytotoxicity of C9orf72-encoding arginine-rich dipeptides. Sci Rep. 2018 Aug 24;8(1):12740. doi: 10.1038/s41598-018-31096-z. PMID: 30143685; PMCID: PMC6109075.

28: Hiraide T, Kataoka M, Suzuki H, Aimi Y, Chiba T, Kanekura K, Satoh T, Fukuda K, Gamou S, Kosaki K. SOX17 Mutations in Japanese Patients with Pulmonary Arterial Hypertension. Am J Respir Crit Care Med. 2018 Nov 1;198(9):1231-1233. doi: 10.1164/rccm.201804-0766LE. PMID: 30044643.

2017以前

27: Clark AL, Kanekura K, Lavagnino Z, Spears LD, Abreu D, Mahadevan J, Yagi T, Semenkovich CF, Piston DW, Urano F. Targeting Cellular Calcium Homeostasis to Prevent Cytokine-Mediated Beta Cell Death. Sci Rep. 2017 Jul 17;7(1):5611. doi: 10.1038/s41598-017-05935-4. PMID: 28717166; PMCID: PMC5514111.

26: Kanekura K, Nishi H, Isaka K, Kuroda M. MicroRNA and gynecologic cancers. J Obstet Gynaecol Res. 2016 Jun;42(6):612-7. doi: 10.1111/jog.12995. Epub 2016 Apr 20. PMID: 27098274.

25: Kanekura K, Yagi T, Cammack AJ, Mahadevan J, Kuroda M, Harms MB, Miller TM, Urano F. Poly-dipeptides encoded by the C9ORF72 repeats block global protein translation. Hum Mol Genet. 2016 May 1;25(9):1803-13. doi: 10.1093/hmg/ddw052. Epub 2016 Feb 29. PMID: 26931465; PMCID: PMC4986334.

24: Lugar HM, Koller JM, Rutlin J, Marshall BA, Kanekura K, Urano F, Bischoff AN, Shimony JS, Hershey T; Washington University Wolfram Syndrome Research Study Group. Neuroimaging evidence of deficient axon myelination in Wolfram syndrome. Sci Rep. 2016 Feb 18;6:21167. doi: 10.1038/srep21167. PMID: 26888576; PMCID: PMC4758056.

23: Vomund AN, Zinselmeyer BH, Hughes J, Calderon B, Valderrama C, Ferris ST, Wan X, Kanekura K, Carrero JA, Urano F, Unanue ER. Beta cells transfer vesicles containing insulin to phagocytes for presentation to T cells. Proc Natl Acad Sci U S A. 2015 Oct 6;112(40):E5496-502. doi: 10.1073/pnas.1515954112. Epub 2015 Aug 31. PMID: 26324934; PMCID: PMC4603448.

22: Kanekura K, Ma X, Murphy JT, Zhu LJ, Diwan A, Urano F. IRE1 prevents endoplasmic reticulum membrane permeabilization and cell death under pathological conditions. Sci Signal. 2015 Jun

23;8(382):ra62. doi: 10.1126/scisignal.aaa0341. PMID: 26106220; PMCID: PMC4492519.

21: Kanekura K, Ou J, Hara T, Zhu LJ, Urano F. Research resource: Monitoring endoplasmic reticulum membrane integrity in β-cells at the single-cell level. Mol Endocrinol. 2015 Mar;29(3):473-80. doi: 10.1210/me.2014-1260. Epub 2015 Jan 13. PMID: 25584413; PMCID: PMC4347291.

20: Lu S, Kanekura K, Hara T, Mahadevan J, Spears LD, Oslowski CM, Martinez R, Yamazaki-Inoue M, Toyoda M, Neilson A, Blanner P, Brown CM, Semenkovich CF, Marshall BA, Hershey T, Umezawa A, Greer PA, Urano F. A calcium-dependent protease as a potential therapeutic target for Wolfram syndrome. Proc Natl Acad Sci U S A. 2014 Dec 9;111(49):E5292-301. doi: 10.1073/pnas.1421055111. Epub 2014 Nov 24. PMID: 25422446; PMCID: PMC4267371.

19: Hara T, Mahadevan J, Kanekura K, Hara M, Lu S, Urano F. Calcium efflux from the endoplasmic reticulum leads to β-cell death. Endocrinology. 2014 Mar;155(3):758-68. doi: 10.1210/en.2013-1519. Epub 2013 Jan 1. PMID: 24424032; PMCID: PMC3929724.

18: Kanekura K, Ishigaki S, Merksamer PI, Papa FR, Urano F. Establishment of a system for monitoring endoplasmic reticulum redox state in mammalian cells. Lab Invest. 2013 Nov;93(11):1254-8. doi: 10.1038/labinvest.2013.112. Epub 2013 Sep 16. PMID: 24042438; PMCID: PMC4090936.

17: Oslowski CM, Hara T, O'Sullivan-Murphy B, Kanekura K, Lu S, Hara M, Ishigaki S, Zhu LJ, Hayashi E, Hui ST, Greiner D, Kaufman RJ, Bortell R, Urano F. Thioredoxin-interacting protein mediates ER stress-induced β cell death through initiation of the inflammasome. Cell Metab. 2012 Aug 8;16(2):265-73. doi: 10.1016/j.cmet.2012.07.005. PMID: 22883234; PMCID: PMC3418541.

16: Kanekura K, Suzuki H, Aiso S, Matsuoka M. ER stress and unfolded protein response in amyotrophic lateral sclerosis. Mol Neurobiol. 2009 Apr;39(2):81-9. doi: 10.1007/s12035-009-8054-3. Epub 2009 Jan 30. PMID: 19184563.

15: Suzuki H, Kanekura K, Levine TP, Kohno K, Olkkonen VM, Aiso S, Matsuoka M. ALS-linked P56S-VAPB, an aggregated loss-of-function mutant of VAPB, predisposes motor neurons to ER stress-related death by inducing aggregation of co-expressed wild-type VAPB. J Neurochem. 2009 Feb;108(4):973-985. doi: 10.1111/j.1471-4159.2008.05857.x. PMID: 19183264.

14: Nakahara J, Kanekura K, Nawa M, Aiso S, Suzuki N. Abnormal expression of TIP30 and arrested nucleocytoplasmic transport within oligodendrocyte precursor cells in multiple sclerosis. J Clin Invest. 2009 Jan;119(1):169-81. doi: 10.1172/JCI35440. Epub 2008 Dec 22. PMID: 19104151; PMCID: PMC2613458.

13: Nawa M, Kanekura K, Hashimoto Y, Aiso S, Matsuoka M. A novel Akt/PKB- interacting protein promotes cell adhesion and inhibits familial amyotrophic lateral sclerosis-linked mutant SOD1-induced neuronal death via inhibition of PP2A-mediated dephosphorylation of Akt/PKB. Cell Signal. 2008 Mar;20(3):493-505. doi: 10.1016/j.cellsig.2007.11.004. Epub 2007 Nov 17. PMID: 18160256.

12: Kawasaki A, Torii K, Yamashita Y, Nishizawa K, Kanekura K, Katada M, Ito M, Nishimoto I, Terashita K, Aiso S, Matsuoka M. Wnt5a promotes adhesion of human dermal fibroblasts by triggering a phosphatidylinositol-3 kinase/Akt signal. Cell Signal. 2007 Dec;19(12):2498-506. doi: 10.1016/j.cellsig.2007.07.023. Epub 2007 Aug 9. PMID: 17804197.

11: Kanekura K, Nishimoto I, Aiso S, Matsuoka M. Characterization of amyotrophic lateral sclerosis-linked P56S mutation of vesicle-associated membrane protein- associated protein B (VAPB/ALS8). J Biol Chem. 2006 Oct 6;281(40):30223-33. doi: 10.1074/jbc.M605049200. Epub 2006 Aug 4. PMID: 16891305.

10: Hashimoto Y, Chiba T, Yamada M, Nawa M, Kanekura K, Suzuki H, Terashita K, Aiso S, Nishimoto I, Matsuoka M. Transforming growth factor beta2 is a neuronal death-inducing ligand for amyloid-beta precursor protein. Mol Cell Biol. 2005 Nov;25(21):9304-17. doi: 10.1128/MCB.25.21.9304-9317.2005. PMID: 16227582; PMCID: PMC1265827.

9: Obata Y, Niikura T, Kanekura K, Hashimoto Y, Kawasumi M, Kita Y, Aiso S, Matsuoka M, Nishimoto I. Expression of N19S-SOD1, an SOD1 mutant found in sporadic amyotrophic lateral sclerosis patients, induces low-grade motoneuronal toxicity. J Neurosci Res. 2005 Sep 1;81(5):720-9. doi: 10.1002/jnr.20594. PMID: 16035108.

8: Kanekura K, Hashimoto Y, Kita Y, Sasabe J, Aiso S, Nishimoto I, Matsuoka M. A Rac1/phosphatidylinositol 3-kinase/Akt3 anti-apoptotic pathway, triggered by AlsinLF, the product of the ALS2 gene, antagonizes Cu/Zn-superoxide dismutase (SOD1) mutant-induced motoneuronal cell death. J Biol Chem. 2005 Feb 11;280(6):4532-43. doi: 10.1074/jbc.M410508200. Epub 2004 Dec 3. PMID: 15579468.

7: Hashimoto Y, Terashita K, Niikura T, Yamagishi Y, Ishizaka M, Kanekura K, Chiba T, Yamada M, Kita Y, Aiso S, Matsuoka M, Nishimoto I. Humanin antagonists: mutants that interfere with dimerization inhibit neuroprotection by Humanin. Eur J Neurosci. 2004 May;19(9):2356-64. doi: 10.1111/j.0953-816X.2004.03298.x. PMID: 15128389.

6: Kanekura K, Hashimoto Y, Niikura T, Aiso S, Matsuoka M, Nishimoto I. Alsin, the product of ALS2 gene, suppresses SOD1 mutant neurotoxicity through RhoGEF domain by interacting with SOD1 mutants. J Biol Chem. 2004 Apr 30;279(18):19247-56. doi: 10.1074/jbc.M313236200. Epub 2004 Feb 16. PMID: 14970233.

5: Hashimoto Y, Tsuji O, Kanekura K, Aiso S, Niikura T, Matsuoka M, Nishimoto I. The Gtx homeodomain transcription factor exerts neuroprotection using its homeodomain. J Biol Chem. 2004 Apr 16;279(16):16767-77. doi: 10.1074/jbc.M313630200. Epub 2004 Jan 29. PMID: 14754886.

4: Tsukamoto E, Hashimoto Y, Kanekura K, Niikura T, Aiso S, Nishimoto I. Characterization of the toxic mechanism triggered by Alzheimer's amyloid-beta peptides via p75 neurotrophin receptor in neuronal hybrid cells. J Neurosci Res. 2003 Sep 1;73(5):627-36. doi: 10.1002/jnr.10703. PMID: 12929130.

3: Terashita K, Hashimoto Y, Niikura T, Tajima H, Yamagishi Y, Ishizaka M, Kawasumi M, Chiba T, Kanekura K, Yamada M, Nawa M, Kita Y, Aiso S, Nishimoto I. Two serine residues distinctly regulate the rescue function of Humanin, an inhibiting factor of Alzheimer's disease-related neurotoxicity: functional potentiation by isomerization and dimerization. J Neurochem. 2003 Jun;85(6):1521-38. doi: 10.1046/j.1471-4159.2003.01797.x. PMID: 12787071.

2: Kawasumi M, Hashimoto Y, Chiba T, Kanekura K, Yamagishi Y, Ishizaka M, Tajima H, Niikura T, Nishimoto I. Molecular mechanisms for neuronal cell death by Alzheimer's amyloid precursor protein-relevant insults. Neurosignals. 2002 Sep-Oct;11(5):236-50. doi: 10.1159/000067424. PMID: 12566925.

1: Hashimoto Y, Tsuji O, Niikura T, Yamagishi Y, Ishizaka M, Kawasumi M, Chiba T, Kanekura K, Yamada M, Tsukamoto E, Kouyama K, Terashita K, Aiso S, Lin A, Nishimoto I. Involvement of c-Jun N-terminal kinase in amyloid precursor protein-mediated neuronal cell death. J Neurochem. 2003 Feb;84(4):864-77. doi: 10.1046/j.1471-4159.2003.01585.x. PMID: 12562529.