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Division of Advanced Medicine for Virus Infections

We aim to develop novel strategies for the diagnosis and treatment of pediatric infectious diseases caused by the herpes virus. We also intend to translate the latest results of molecular virology into clinical practice. Epstein-Barr virus (EBV) is the primary target of our research.

The main responsibilities of our department are:

Generating mouse models for diseases associated with EBV

EBV causes a number of diseases in children, such as infectious mononucleosis, chronicactive EBV infection, and white blood cell or lymphoproliferative diseases in patients with compromised immune systems. We utilize 'humanized mouse' technology to prepare mouse models of EBV infection that are suitable for the evaluation of drugs and vaccines. Humanized mice are prepared by reconstituting human immune system components in immunodeficient mice. These mice are then able to be infected with EBV and reproduce EBV-associated diseases, such as lymphoproliferative disease. By using this model, we are able to evaluate novel drugs and therapies to treat EBV.

Diagnosis of virus infections

We routinely undertake molecular diagnosis of various virus infections. In particular, we practice molecular EBV monitoring in transplant recipients and identify EBV-infected cells for the diagnosis of chronic active EBV infection. We also use rapid assay technology to diagnose childhood viruses (except EBV) including herpes simplex types 1 and 2, cytomegalovirus, human herpes virus types 6 and 7, and hepatitis B virus, among others.

Development of highly advanced medical techniques and treatments

Our department is devoted to the development of new therapeutic drugs to treat virus infections, new diagnostic procedures and therapies


Members

Leaders

Researchers

  • Yuriko Ishikawa

Doctors

  • Masaki Yamada
  • Jun Abe
  • Reiko Ito
  • Kei Sakamoto

Assistant Researchers

  • Mari Shimura
  • Eri Ito
  • Etsuko Takahashi
  • Naomi Misawa
  • Yuki Yoshikawa
  • Fuyuko Kawano
  • Akemi Tarumi

Clinical Technologists

  • Azusa Tasaka
  • Naomi Wada

Assistants

  • Masumi Hamada

Research Collaborators

  • Shino Suzuki
  • Ayano Ito
  • Miwa Matsuzu
  • Yu Uemura
  • Ryo Nasu
  • Ayaka Ohashi
  • Lily Tsuyuki

Bibliography

2021

    1. Hosoi H., Mushino T, Nakashima K, Kuriyama K, Tamura S, Murata S, Imadome KI, Ohshima K, Sonoki T. Composite Epstein-Barr Virus-associated T-lymphoblastic and Peripheral T-cell Lymphomas: A Clonal Study. Intern Med.2021; 60(13):2119-2123.
    2. Nagasawa Y, Takei M, Iwata M, Nagatsuka Y, Tsuzuki H, Imai K, Imadome KI, Fujiwara S, Kitamura N. Human osteoclastogenesis in Epstein-Barr virus-induced erosive arthritis in humanized NOD/Shi-scid/IL-2Rgammanull mice. PLoS One. 2021;16(4):e0249340.
    3. Sakata N, Okano M., Masako R, Tanaka A, Yamashita Y, Karasuno T, Imadome KI, Okada M, Sugimoto K.Donor-derived myelodysplastic syndrome after allogeneic stem cell transplantation in a family with germline GATA2 mutation. Int J Hematol. 2021;113(2):290-296.
    4. Yamada M, Funaki T, Shoji K, Miyairi I, Fukuda A, Sakamoto S, Imadome KI, Kasahara M. Do Not Delay: Safe Operation for Pediatric Living-donor Liver Transplantation Programs in the COVID-19 Era. Transplantation. 2021;105(3):e39-e40.
    5. Yoshimori M, Shibayama H, Imadome KI, Kawano F, Ohashi A, Nishio M, Shimizu N, Kurata M, Fujiwara S, Arai A. Antineoplastic and anti-inflammatory effects of bortezomib on systemic chronic active EBV infection. Blood Adv. 2021;5(7):1805-1815.
    6. Cui X, Cao Z, Ishikawa Y, Cui S, Imadome KI, Snapper C. M. Immunization with Epstein-Barr Virus Core Fusion Machinery Envelope Proteins Elicit High Titers of Neutralizing Activities and Protect Humanized Mice from Lethal Dose EBV Challenge. Vaccines (Basel). 2021;9(3)：285.
    7. Yamada M, Sakamoto S, Sakamoto K, Uchida H, Shimizu S, Osumi T, Kato M, Shoji K, Arai K, Miyazaki O, Nakano N, Yoshioka T, Fukuda A, Kasahara M, Imadome KI. Fatal Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis with virus-infected T cells after pediatric multivisceral transplantation. A proof-of-concept case report. Pediatr Transplant. 2021;25(3):
      e13961.
    8. Yamada M, Ishikawa Y, Imadome KI. Hypersensitivity to mosquito bites:A versatile Epstein-Barr virus disease with allergy, inflammation, and malignancy. Allergol Int. 2021；70(4):430-438.
    9. Yamada M, Sakamoto K, Tomizawa D, Ishikawa Y, Matsui T, Gocho Y, Sakaguchi H, Kato M, Osumi T, Imadome KI. A prospective viral monitoring study 　following pediatric allogeneic hematopoietic stem cell transplantation for malignant and nonmalignant diseases. Transplant Cell Ther. 2021；27（10）：872.e1-872.e8.
    10. Shimizu S, Sakamoto S, Yamada M, Fukuda A, Yanagi Y, Uchida H, Mimori K, Shoji K, Funaki T, Miyairi I, Nakano N, Haga C, Yoshioka T, Imadome KI, 　Horikawa R, Kasahara M. Immunological features and complications in patients with glycogen storage disease 1b after living donor liver transplantation. Pediatr Transplant. 2021:e14104.
    11. Yoshimori M, Nishio M, Ohashi A, Tateishi M, Mimura A, Wada N, Saito M, Shimizu N, Imadome KI, Arai A. Interferon-gamma Produced by EBV-Positive Neoplastic NK-Cells Induces Differentiation into Macrophages and Procoagulant Activity of Monocytes, Which Leads to HLH. Cancers (Basel). 2021;13(20) 5097.
    12. Akazawa R, Otsuka S, Kato I, Imadome KI, Takita J. Transient remission of chronic active EBV infection after chemotherapy alone. Pediatr Int. 2022 ; 64(1):e14836.

2020

    1. Ikenori M, Yotani N, Yamada M, Imadome KI, Miyairi I, Ishiguro A. Eleven-year-old girl with acute genital ulcers Was it sexual abuse? J Paediatr Child Health. 2020；56（12）：1995-1996.

    2. Abe R, Kato J, Hashida R, Yamane Y, Koda Y, Kikuchi T, Imadome KI, Inoue M, Sasaki A, Kameyama K, Mori T. [Chronic active Epstein-Barr virus infection with multiple vascular lesions successfully treated by cord blood transplantation.] Rinsho Ketsueki.2020; 61 (10):1502-1507.

    3. Osumi T, Yoshimura S, Sako M, Uchiyama T, Ishikawa T, Kawai T, Inoue E, Takimoto T, Takeuchi I , Yamada M , Sakamoto K, Yoshida K, Kimura Y, Matsukawa Y, Matsumoto K, Imadome KI, Arai K, Deguchi T, Imai K, Yuza Y, Matsumoto K, Onodera M, Kanegane H, Tomizawa D, Kato M. 　Prospective Study of Allogeneic Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide and Antithymocyte Globulin from HLA-Mismatched Related Donors for Nonmalignant Diseases. Biol Blood Marrow Transplant. 2020；26(11):e286-e291.

    4. Sakamoto A, Yamada M, Tsujimoto S, Osumi T, Arai K, Tomizawa D, Ishiguro A, Matsumoto K, Imadome KI , Kato M.　A case of human herpesvirus 6 encephalitis following pediatric hematopoietic stem cell transplantation: early diagnosis and treatment matters. Int J Hematol.2020；112(5):751-754.

    5. Kawaguchi S, Sato K, Oshiro H, Imadome KI., Kanda Y. Recurrent Enteritis Associated with Epstein-Barr virus-positive CD4+ T-cell Lymphoproliferative Disorder after Autologous Stem Cell Transplantation. Intern Med. 2020；59(20):2565-2569.

    6. Yonese I, Sakashita C, Imadome KI, Kobayashi T, Yamamoto M, Sawada A, Ito Y, Fukuhara N, Hirose A, Takeda Y, Makita M, Endo T, Kimura S,Ishimura M, Miura O, Ohga S, Kimura H, Fujiwara S, Arai A. Nationwide survey of systemic chronic active EBV infection in Japan in accordance with the new WHO classification.Blood Adv. 2020；4 (13): 2918-2926.

    7. Nishiyama K, Watanabe Y, Ishimura M, Tetsuhara K, Imai T, Kanemasa H,Ueki K, Motomura Y, Kaku Y, Sakai Y, Imadome KI, Ohga S. Parvovirus B19-infected tubulointerstitial nephritis in hereditary spherocytosis　Open Forum Infect Dis. 2020 ;7(8):288.

    8. Okamoto M, Ichinose K, Sato S, Imadome KI, Furukawa K, Kawakami A. A case of γδ T-cell large granular lymphocytic leukemia due to a chronic Epstein-Barr virus infection in systemic lupus erythematosus.Clin Immunol. 2020； 214:108378.

    9. Kotaki R, Kawashima M, Yamamoto Y, Higuchi H, Nagashima E, Kurosaki N, Takamatsu M, Kikuti Y, Imadome KI, Nakamura N, Kotani A. Dasatinib exacerbates splenomegaly of mice inoculated with Epstein-Barr virus-infected lymphoblastoid cell lines. Sci Rep. 2020 ;10(1):4355.

2019

  1. Hosaka S, Kobayashi C, Saito H, Imai-Saito A, Suzuki R, Iwabuchi A, Kato Y, Jimbo T, Watanabe N, Onodera M, Imadome KI, Masumoto K, Nanmoku T, Fukushima T, Kosaki K, Sumazaki R, Takada H. Establishment of immunity against Epstein-Barr virus infection in a patient with CHARGE/complete DiGeorge syndrome after peripheral blood lymphocyte transfusion. Pediatr Transplant. 2019;23(4):e13424.
  2. Ishimura M, Eguchi K, Shiraishi A, Sonoda M, Azuma Y, Yamamoto H, Imadome KI, Ohga S. Systemic Epstein-Barr Virus-Positive T/NK Lymphoproliferative Diseases with SH2D1A/XIAP Hypomorphic Gene Variants. Front Pediatr.2019； 7:183.
  3. Katahira Y, Higuchi H, Matsushita H, Yahata T, Yamamoto Y, Koike R, Ando K, Sato K, Imadome KI, Kotani A.Increased Granulopoiesis in the Bone Marrow following Epstein-Barr Virus Infection. Sci Rep. 2019;9(1):13445.
  4. Kusano N, Sakata N, Sugimoto K, Miyazawa T, Ueda S, Okano M, Imadome KI, Hoshino A, Kanegane H, Kimura M, Sato T, Okada M, Takemura T. An 18-Year-Old Male With X-linked Lymphoproliferative Syndrome Type 1 Who Developed Primary Central Nervous System Lymphoma 6 Months After Primary Epstein-Barr Virus Infection. J Pediatr Hematol Oncol. 2019； 41(8):e538-e541.
  5. Osumi T, Tomizawa D, Kawai T, Sako M, Inoue E, Takimoto T, Tamura E, Uchiyama T, Imadome KI, Taniguchi M, Shirai R, Yoshida M, Ando R, Tsumura Y, Fuji H, Matsumoto K, Shioda Y, Kiyotani C, Terashima K, Onodera M, Matsumoto K, Kato M. A prospective study of allogeneic transplantation from unrelated donors for chronic granulomatous disease with target busulfan-based reduced-intensity conditioning. Bone Marrow Transplant. 2019;54(1):168-172.
  6. Sakaki S, Imadome KI, Kawano F, Nakadate H, Ishiguro A. Shift in Epstein-Barr virus (EBV)-infected cells in chronic active EBV disease. Pediatr Int. 2019；61 (8):825-6.
  7. Shoji K, Imadome KI, Miyairi I, Yoshida K, Ishiguro A. Multiple round ulcers after mosquito bites in a pediatric patient with chronic active EBV infection. Pediatr Int. 2019;61(1):109-10.
  8. Tanita K, Hoshino A, Imadome KI, Kamiya T, Inoue K, Okano T, Yeh Ｔ, Yanagaimachi Ｍ, ShiraishiＡ, Ishimura M, Schober T,Rohlfs M, Takagi M, Imai K, Tkakada H, Ohga S, Klein C, Morio T,Kanegane T.Epstein-Barr Virus-Associated gammadelta T-Cell Lymphoproliferative Disorder Associated with Hypomorphic IL2RG Mutation. Front Pediatr. 2019;7:15.
  9. Yamashita Y, Nishikawa A, Iwahashi Y, Fujimoto M, Sasaki I, Mishima H, Kinoshita A, Hennmi H, Kanazawa N, Oshima K, Imadome KI, Murata S, Yoshiura KI, Kaisho F, Sonoki T, Tamura S. Identification of a novel CCDC22 mutation in　a patient with severe Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis and aggressive natural killer cell leukemia. Int J Hematol. 2019;109(6):744-50.
  10. Yatsushiro Y, Nishikawa T, Saito A, Nakazawa Y, Imadome KI, Nakagawa S, Kodama Y, Okamoto Y, Kanegane H, Kawano Y. Epstein-Barr Virus (EBV)-induced B-cell Lymphoproliferative Disorder Mimicking the Recurrence of EBV-associated Hemophagocytic Lymphohistiocytosis. J Pediatr Hematol Oncol. 2019;41(1):e44-e46
  11. Fujimori K, Yamada M, Maekawa T, Yotani N, Tamura EI, Imadome KI, KubotaM, IshiguroA. A case of neonatal cytomegalovirus infection with severe　thrombocytopenia that was successfully managed with empiric antiviral therapy. IDCases. 2019;19:e00675.

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