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【Labs spotlight】 Hoshino Laboratory

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June 1, 2020

Ayuko Hoshino

Life Science and Technology Graduate Major
Associate Professor Ayuko Hoshino別窓

Office Room 509, B1B2 building, Suzukakedai campus
Degree PhD 2011, The University of Tokyo
Areas of Research Exosome Biology, Cancer Metastasis, Neurodevelopmental Disease, Autism, Biomarker
Keywords Exosome, Cancer, Metastasis, Autism, neurodegenerative disease, maternal-embryonic interaction

Research interest

 Exosomes, nanosized vesicles mediating cell-cell communication, play roles in normal physiology and disease etiology. We aim to elucidate the mechanisms through which exosomes drive disease pathology. Ultimately, we plan to target exosome cargo and pathological signaling pathways activated by exosomes, and to develop novel treatments for neurodevelopmental diseases and cancer.

Cancer-derived exosomes determine future site of metastasis

Figure 1.Cancer-derived exosomes determine future site of metastasis

Cancer-derived exosomes fuse with specific cells at future site of metastasis. Hoshino et al., Nature 2015 Rodrigues, Hoshino et al. (co-first author), Nature Cell Biology 2019
Hoshino et al., Nature 2015 Rodrigues, Hoshino et al. (co-first author), Nature Cell Biology 2019
We aim to further elucidate the role of specific exosomes in cancer progression.


Exosome as organ to organ communication tool

Figure 2.Exosome as organ to organ communication tool

Multiple pathology related exosomes pass through blood brain barrier and affect brain microenvironment.

We aim to characterize the role exosomes play in neurodevelopmental disorder, especially autism.


Maternal exosomes and embryonic interaction

Figure 3.Maternal exosomes and embryonic interaction

Maternal exosomes influence embryonic development.
We aim to characterize maternal exosomes and how exosomal protein plays a role in pregnancy and embryonic development.

Selected publications

  1. 1.Hoshino A, Sang Kim H, Bojmar L, Ennu Gyan K, Cioffi M, Hernandez J, Zambirinis CP, Rodrigues G, Molina H, Heissel S, Tesic Mark M, Steiner L, Benito-Martin A, Lucotti S, Di Giannatale A, Offer K, Nakajima M, Williams C, Nogués L, Pelissier Vatter FA, Hashimoto A, Davies AE, Freitas D, Kenific C, Ararso Y, Buehring W, Lauritzen P, Ogitani Y, Sugiura K, Takahashi N, Aleckovic M, Bailey KA, Jolissant JS, Wang H, Harris A, Schaeffer LM, Posner Z, Balachandran VP, Khakoo Y, Raju P, Scherz A, Sagi I, Scherz-Shouval R, Yarden Y, Oren M, Petriccione M, De Braganca K, Donzelli M, Fischer C, Vitolano S, Wright G, Ganshaw L, Marrano M, Ahmed A, DeStefano J, Danzer E, Roehrl MH, Lacayo NJ, Vincent T, Weiser MR, Brady MS, Meyers P, Wexler LH, Ambati S, Chou AJ, Slotkin E, Modak S, Roberts S, Basu E, Diolaiti D, Krantz B, Cardoso F, Simpson AL, Berger M, Rudin CM, Simeone DM, Jain M, Ghajar CM, Batra SK, Stanger BZ, Bui J, Brown KA, Rajasekhar VK, Healey JH, de Sousa M, Kramer K, Sheth S, Baisch J, Pascual V, Heaton TE, La Quaglia MP, Pisapia DJ, Schwartz R, Zhang H, Liu Y, Shukla A, Sarte L, DeClerck Y, LaBarge M, Bissell MJ, Grandgenett P, Hollingsworth M, Bromberg J, Costa-Silva B, Peinado H, Kang Y, Garcia BA, O'Reilly E, Kelsen D, Trippett TM, Jones DR, Matei I, Jarnagin WR, Lyden D. Extracellular Vesicle and Particle biomarkers define multiple human cancers. Cell in press (First and Corresponding author).
  2. 2.Rodrigues G*, Hoshino A*, Matei IR, Scandariato I, Kenific CM, Kim HS, Casanova-Salas I, Dai D, Badwe CR, Gril B, Mark MT, Dill BD, Molina H, Benito-Martin A, Bojmar L, Offer K, LaPlant Q, Ararso Y, Buehring W, Wang H, Juan X, Liu Y, Sabari JK, Shin SJ, Narula N, Rajasekhar VK, Zhang H, Costa-Silva B, Rafii S, Rudin CM, Jones DR, Steeg PS, Peinado H, Ghajar CM, Bromberg J, Pisapia D, de Sousa M, Lyden D. Tumour exosomal KIAA1199 protein promotes cancer cell colonization in brain metastasis. Nature Cell Biology 2019 Nov 4 (Co-first author)
  3. 3.Prakash V, Carson BB, Feenstra JM, Dass RA, Sekyrova P, Hoshino A, Petersen J, Guo Y, Parks MM, Kurylo CM, Batchelder JE, Haller K, Hashimoto A, Rundqivst H, Condeelis JS, Allis CD, Drygin D, Nieto MA, Andang M, Percipalle P, Bergh J, Adameyko I, Farrants AO, Hartman J, Lyden D, Pietras K, Blanchard SC, Vincent CT. Ribosome biogenesis during cell cycle arrest fuels EMT in development and disease. Nat Commun. 2019 May 8;(1):2110
  4. 4.Wittkowski KM, Dadurian C, Seybond MP, Kim HS, Hoshino A, Lyden D. Complex polymorphisms in endocytosis genes suggest alpha-cyclodextrin as a treatment for breast cancer. PLoS One. 2018 Jul 2;13(7):e0199012
  5. 5.Zhang H, Freitas D, Kim HS, Fabijanic K, Li Z, Chen H, Mark MT, Molina H, Martin AB, Bojmar L, Fang J, Rampersaud S, Hoshino A, Matei I, Kenific C, Nakajima M, Mutvei AP, Sansone P, Buehring W, Wang H, Jimenez JP, Cohen-Gould L, Paknejad N, Brendel M, Manova-Todorova K, Magalhaes A, Ferreira JA, Osorio H, Silva AM, Massay A, Cubillos-Ruiz JR, Galletti G, Giannakakou P, Cuervo AM, Blenis J, Schwartz R, Brady MS, Peinado H, Bromberg J, Matsui H, Reis CA, Lyden D. Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric-flow field-flow fractionation. Nature Cell Biology 2018 Mar20(3):332-343
  6. 6.Sansone P, Savini C, Kurelac I, Chang Q, Amato LB, Strillacci A, Stepanova A, Lommarini L, Mastroleo C, Daly L, Galkin A, Thakur BK, Soplop N, Uryu K, Hoshino A, Norton L, Bonafe M, Cricca M, Gasparre G, Lyden D, Bromberg J. Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer. Proc Natl Acad Sci USA 2017 Oct 24; 111(43):E9066-E9075
  7. 7.Hoshino A, Lyden D. Metastasis: Lymphatic detours for cancer. Nature 2017 Jun 28;546(7660):609-610
  8. 8.Peinado H, Zhang H, Matei IR, Costa-Silva B, Hoshino A, Rodrigues G, Psaila B, Kaplan RN, Bromberg JF, Kang Y, Bissell MJ, Cox TR, Giaccia AJ, Erler JT, Hiratsuka S, Ghajar CM, Lyden D. Pre-metastatic niches: organ-specific homes for metastases. Nature Reviews Cancer 2017 May;17(5):302-317
  9. 9.Rampersaud S, Fang J, Wei Z, Fabijanic K, Silver S, Jaikaran T, Ruiz Y, Houssou M, Yin Z, Zheng S, Hashimoto A, Hoshino A, Lyden D, Mahajan S, Matsui H. The effect of cage shape on nanoparticle-based drug carriers: Anti-cancer drug release and efficacy via receptor blockade using dextran-coated iron oxide nanocages. Nano Letters 2016 Dec 14;16(12):7357-7363
  10. 10.Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, Molina H, Kohsaka S, Di Giannatale A, Ceder S, Singh S, Williams C, Soplop N, Uryu K, Pharmer L, King T, Bojmar L, Davies AE, Ararso Y, Zhang T, Zhang H, Hernandez J, Weiss JM, Dumont-Cole VD, Kramer K, Wexler LH, Narendran A, Schwartz GK, Healey JH, Sandstrom P, Jorgen Labori K, Kure EH, Grandgenett PM, Hollingsworth MA, de Sousa M, Kaur S, Jain M, Mallya K, Batra SK, Jarnagin WR, Brady MS, Fodstad O, Muller V, Pantel K, Minn AJ, Bissell MJ, Garcia BA, Kang Y, Rajasekhar VK, Ghajar CM, Matei I, Peinado H, Bromberg J, Lyden D. Tumour exosome integrins determine organotropic metastasis. Nature 2015 Nov 19;527(7578):329-35
  11. 11.Costa-Silva B, Aiello NM, Ocean AJ, Singh S, Zhang H, Thakur BK, Becker A, Hoshino A, Mark MT, Molina H, Xiang J, Zhang T, Theilen TM, Garcia-Santos G, Williams C, Ararso Y, Huang Y, Rodrigues G, Shen TL, Labori KJ, Lothe IM, Kure EH, Hernandez J, Doussot A, Ebbesen SH, Grandgenett PM, Hollingsworth MA, Jain M, Mallya K, Batra SK, Jarnagin WR, Schwartz RE, Matei I, Peinado H, Stanger BZ, Bromberg J, Lyden D. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nature Cell Biology 2015 Jun;17(6):816-26
  12. 12.Thakur BK, Zhang H, Becker A, Matei I, Huang Y, Costa-Silva B, Zheng Y, Hoshino A, Brazier H, Xiang J, Williams C, Rodriguez-Barrueco R, Silva JM, Zhang W, Hearn S, Elemento O, Paknejad N, Manova-Todorova K, Welte K, Bromberg J, Peinado H, Lyden D. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Research 2014 Jun;24(6):766-9
  13. 13.Ishii G, Hashimoto H, Atsumi N, Hoshino A, Ochiai A. Morphophenotype of floating colonies derived from a single cancer cell has a critical impact on tumor-forming activity. Pathol Int. 2013 Jan;63(1):29-36
  14. 14.Peinado H, Ale?kovi? M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, Hergueta-Redondo M, Williams C, Garcia-Santos G, Ghajar CM, Nitadori-Hoshino A, Hoffman C, Badal K, Garcia BA, Callahan MK, Yuan J, Martins VR, Skog J, Kaplan RN, Brady MS, Wolchok JD, Chapman PB, Kang Y, Bromberg J, Lyden D. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nature Medicine 2012 Jun;18(6):883-91
  15. 15.Ito S, Ishii G, Hoshino A, Hashimoto H, Neri S, Kuwata T, Higashi M, Nagai K, Ochiai A. Tumor promoting effect of podoplanin-positive fibroblasts is mediated by enhanced RhoA activity. Biochem Biophys Res Commun. 2012 May25; 422(1):194-9
  16. 16.Hoshino A, Ishii G, Ito T, Aoyagi K, Ohtaki Y, Nagai K, Sasaki H, and Ochiai A. Podoplanin-positive fibroblasts enhance lung adenocarcinoma tumor formation. Cancer Research 2011 Jul 15;71(14):4769-79
  17. 17.Ishii G, Hashimoto H, Asada K, Ito T, Hoshino A, Fujii S, Kojima M, Kuwata T, Harigaya K, Nagai K, Ushijima T, and Ochiai A. Fibroblasts associated with cancer cells keep enhanced migration activity after separation from cancer cells: a novel character of tumor educated fibroblasts. Int J Oncol. 2010 Aug;37(2):317-25
  18. 18.Ito TK, Ishii G, Saito S, Yano K, Hoshino A, Suzuki T, and Ochiai A. Degradation of soluble VEGF receptor-1 by MMP-7 allows VEGF access to endothelial cells. Blood 2009 Mar 5;113(10):2363-9
  19. 19.Hoshino A, Chiba H, Nagai K, Ishii G, and Ochiai A. Human vascular adventitial fibroblasts contain mesenchymal stem/progenitor cells. Biochem Biophys Res Commun. 2008 Apr 4;368(2):305-10.

Contact

Associate Professor Toshinori Fujie

Room 509, B1B2 building, Suzukakedai campus

E-mail : ayukohoshino@bio.titech.ac.jp

*Find more about the lab and the latest activities at Hoshino Laboratoryouter

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