国立研究開発法人 国立成育医療研究センター National Center for Child Health and Development

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Scholar & Enterprise

Scholar & Enterprise

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
  • Naomi Wada
  • Etsuko Takahashi
  • Naomi Misawa
  • Yuki Yoshikawa
  • Fuyuko Kawano

Clinical Technologists

  • Azusa Tasaka

Assistants

  • Mayuko Morita
  • Akemi Tarumi

Research Collaborators

  • Miyuki Ogura
  • Sayaka Miura
  • Shino Suzuki
  • Hideto Ansai
  • Akihiro Matsunaga
  • Yu Uemura
  • Ryo Nasu
  • Shugo Hirashima
  • Ayaka Shiraga
  • Risa Numasaki
  • Shinji Kunishima
  • Kazuaki Kameda
  • Ayaka Ohashi

Bibliography

2019

  1. Hosaka S, Kobayashi C, Saito H, Imai-Saito A, Suzuki R, Iwabuchi A, Kato Y, Jimbo T, Watanabe N, Onodera M,〇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 , Yamamoto H, 〇 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, 〇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, 〇 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,〇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, 〇Imadome KI, Kamiya T, Inoue K, Okano T, et al. 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,〇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, 〇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-e6
  11. Kotaki R, Kawashima M, Yamamoto Y, Higuchi H, Nagashima N, Kurosaki N,Takamatsu M,Kikuti Y.Y, 〇Imadome KI. Nakamura N & Kotani A. Dasatinib exacerbates splenomegaly of mice inoculated with Epstein-Barr virus-infected lymphoblastoid cell lines. Scientific Reports.2020; 10: 4355.
  12. Okamoto M, Ichinose K, Sato S, 〇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 Mar 4;214:108378.
  13. Fujimori K, Yamada M, Maekawa T, Yotani N, Tamura EI, 〇Imadome KI , KubotaM,Ishiguro A. A case of neonatal cytomegaloviruss infection with severe thrombocytopenia that was successfully managed with empiric antiviral therapy.2019 Nov 23;19:e00675. eCollection 2020.

2018

  1. Imadome KI,Higuchi H, Yamakawa N, Yahata T, Kotaki R, Ogata J, et al. Role of exosomes as a proinflammatory mediator in the development of EBV-associated lymphoma. Blood. 2018;131(23):2552-67.
  2. Hoshino A, Tanita K, Kanda K, Imadome KI, 〇Imadome KI, Shikama Y, Yasumi T, et al. High frequencies of asymptomatic Epstein-Barr virus viremia in affected and unaffected individuals with CTLA4 mutations. Clin Immunol. 2018;195:45-8.
  3. Koizumi Y, 〇Imadome KI, Ota Y, Minamiguchi H, Kodama Y, Watanabe D, et al. Dual Threat of Epstein-Barr Virus: an Autopsy Case Report of HIV-Positive Plasmablastic Lymphoma Complicating EBV-Associated Hemophagocytic Lymphohistiocytosis. J Clin Immunol. 2018;38(4):478-83.
  4. Nakanishi K, Kaito H, Ogi M, Takai D, Fujimura J, Horinouchi T, 〇 Imadome KI, et al. Three Severe Cases of Viral Infections with Post-Kidney Transplantation Successfully Confirmed by Polymerase Chain Reaction and Flow Cytometry. Case Rep Nephrol Dial. 2018;8(3):198-206.
  5. Okazaki K, 〇Imadome KI, Nakao H, Miyairi I, Ishiguro A. Quantitative PCR Assays of Cytomegalovirus and Epstein-Barr Virus in Hemophagocytic Lymphohistiocytosis. Indian J Pediatr. 2018;85(7):593-4.
  6. Tokoro S, Namiki T, Miura K, Watanabe K, Arai A, 〇Imadome KI, et al. Chronic active Epstein-Barr virus infection with cutaneous lymphoproliferation: haemophagocytosis in the skin and haemophagocytic syndrome. J Eur Acad Dermatol Venereol. 2018;32(3):e116-e7.
  7. Onozawa E, Shibayama H, Takada H, 〇Imadome KI, Aoki S, Yoshimori M, et al. STAT3 is constitutively activated in chronic active Epstein-Barr virus infection and can be a therapeutic target. Oncotarget. 2018;9(57):31077-89.
  8. Yoshida M, Osumi T, 〇Imadome KI, Tomizawa D, Kato M, Miyazawa N, et al. Successful treatment of systemic EBV positive T-cell lymphoma of childhood using the SMILE regimen. Pediatr Hematol Oncol. 2018;35(2):121-4.
  9. Yoshimori M, 〇Imadome KI, Tomii S, Yamamoto K, Miura O, Arai A. Cerebrospinal fluid findings in chronic active Epstein-Barr virus infection with central nervous system involvement. Rinsho Ketsueki. 2018;59(4):367-72.
  10. Toriihara A, Arai A, Nakadate M, Yamamoto K, 〇Imadome KI, Miura O, et al. FDG-PET/CT findings of chronic active Epstein-Barr virus infection. Leuk Lymphoma. 2018;59(6):1470-3.

2017

  1. Haji S, Shiratsuchi M, Matsushima T, Takamatsu A, Tsuda M, Tsukamoto Y, 〇Imadome KI, et al. Achievement of disease control with donor-derived EB virus-specific cytotoxic T cells after allogeneic peripheral blood stem cell transplantation for aggressive NK-cell leukemia. Int J Hematol. 2017;105(4):540-4.
  2. Hosoi H, 〇Imadome KI, Tamura S, Kuriyama K, Murata S, Yamashita Y, et al. An Epstein-Barr virus susceptible immature T-cell line, WILL4, established from a patient with T-lymphoblastic lymphoma bearing CD21 and a clonal EBV genome. Leuk Res. 2017;55:1-5.
  3. Imadome KI, Fujiwara S. Generation and Analysis of Humanized Mouse Model of EBV Infection. Methods Mol Biol. 2017;1532:241-54.
  4. Imai A, Takase H, 〇Imadome KI, Matsuda G, Ohnishi I, Yamamoto K, et al. Development of Extranodal NK/T-cell Lymphoma Nasal Type in Cerebrum Following Epstein-Barr Virus-positive Uveitis. Intern Med. 2017;56(11):1409-14.
  5. Kurokawa Y, Masuda H, Kobayashi T, Ono H, Kato H, 〇Imadome KI, et al. Effective therapy with infliximab for clinically mild encephalitis/encephalopathy with a reversible splenial lesion in an infant with Kawasaki disease. Nihon Rinsho Meneki Gakkai Kaishi. 2017;40(3):190-5.
  6. Motomura K, Okada N, Morita H, Hara M, Tamari M, Orimo K, 〇Imadome KI, et al. A Rho-associated coiled-coil containing kinases (ROCK) inhibitor, Y-27632, enhances adhesion, viability and differentiation of human term placenta-derived trophoblasts in vitro. PLoS One. 2017;12(5):e0177994.
  7. Nariai R, Kobayashi T, Masuda H, Ono H, 〇Imadome KI, Kubota M, et al. Transient detection of lupus anticoagulant in acute phase of Kawasaki disease. Nihon Rinsho Meneki Gakkai Kaishi. 2017;40(6):456-9.
  8. Onozawa E, Shibayama H, 〇Imadome KI, Tsuzura A, Koyama T, Miura O, et al. Inflammatory cytokine production in chronic active Epstein-Barr virus infection. Rinsho Ketsueki. 2017;58(3):189-96.
  9. Shibayama H, 〇Imadome KI, Onozawa E, Tsuzura A, Miura O, Koyama T, et al. Virus-specific cytotoxic T cells in chronic active Epstein-Barr virus infection. Rinsho Ketsueki. 2017;58(6):583-8.
  10. Takada H, 〇Imadome KI, Shibayama H, Yoshimori M, Wang L, Saitoh Y, et al. Correction: EBV induces persistent NF-kappaB activation and contributes to survival of EBV-positive neoplastic T- or NK-cells. PLoS One. 2017;12(8):e0182682.
  11. Takada H, 〇Imadome KI, Shibayama H, Yoshimori M, Wang L, Saitoh Y, et al. EBV induces persistent NF-kappaB activation and contributes to survival of EBV-positive neoplastic T- or NK-cells. PLoS One. 2017;12(3):e0174136.
  12. Yamada Y, Osumi T, 〇Imadome KI, Takahashi E, Ohye T, Yoshikawa T, et al. Transmission of chromosomally integrated human herpesvirus 6 via cord blood transplantation. Transpl Infect Dis. 2017;19(1).
  13. Yamaguchi H, Ishida T, Yokoi T, Tanaka T, Maruyama A, Nagase H, 〇Imadome KI, et al. Clinically Mild Encephalitis/Encephalopathy With a Reversible Splenial Lesion Accompanied by Epstein-Barr Virus Hemophagocytic Lymphohistiocytosis: A Case Report and Review of the Literature. J Pediatr Hematol Oncol. 2017;39(2):e92-e6.