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

Department of Human Genetics

We aim to identify causative genes for child intractable hereditary diseases and analyze their functions to develop new gene-based therapeutic treatments.

1. Stem cell gene therapy for primary immunodeficiencies

In collaboration with the National Institutes of Health (USA), we are conducting a clinical trial of stem cell gene therapy for chronic granulomatous disease using a retroviral vector. We also coordinate clinical trials of lentiviral-based gene therapy for Wiskott-Aldrich syndrome and X-linked severe combined immunodeficiency. We employ next-generation DNA sequencing and digital polymerase chain reactions (PCR) to evaluate the safety of gene therapy clinical trials, to ensure quality control of the clinical vectors and to analyze vector integration sites.

2. Establishment of disease-specific iPS cells

We establish specific iPS cells from peripheral blood or skin fibroblasts obtained from patients with intractable hereditary diseases such as primary immunodeficiencies and congenital metabolic disorders.
We perform detailed morbidity analysis and investigate inheritable genetic-modification using established iPS cells.

3. Gene therapy for congenital metabolic disorders

Lysosomal diseases including Niemann-Pick disease and mucopolysaccharidosis are good targets for gene therapy. We are currently developing a new strategy of Adeno-associated virus (AAV) vector-mediated gene delivery for these diseases.

4. Basic research of viral vectors

We carry out the cloning of transcriptional repressors of human origin and study the inhibition mechanism of gene expression using retroviral vectors.
We are developing safer viral vectors with high curative effects for future gene therapy clinical trials.

5. NCCHD BioBank

We store iPS cells from child intractable hereditary diseases as a bioresource in the NCCHD BioBank and support the BioBank in various research endeavors, including drug design and development.




  • Toru Yasuda
  • Akane Miura



  1. Uchiyama T, Sirirat Takahashi S, Nakabayashi K, Okamura K, Edasawa K, Yamada M, Watanabe N, Mochizuki E, Yasuda T, Miura A, Kato K, Tomizawa D, Otsu M, Ariga T, Onodera M. Nonconditioned ADA-SCID gene therapy reveals ADA requirement in the hematopoietic system and clonal dominance of vector-marked clones. Molecular Therapy: Methods & Clinical Development 2021 Oct 16;23:424-433. doi: 10.1016/j.omtm.2021.10.003.
  2. Ishikawa T, Okai M, Mochizuki E, Uchiyama T, Onodera M, Kawai T. Bacillus Calmette-Guerin (BCG) infections at high frequency in both AR-CGD and X-CGD patients following BCG vaccination. Clin Infect Dis 2021 Nov 2;73(9):e2538-e2544. doi: 10.1093/cid/ciaa1049.
  3. Ishikawa K, Uchiyama T, Kaname T, Kawai T, Ishiguro A. Autoimmune hemolytic anemia associated with Takenouchi-Kosaki syndrome. Pediatr Int. 2021 Dec;63(12):1528-1530. doi: 10.1111/ped.14651.
  4. Kanamaru Y, Uchiyama T, Kaname T, Yanagi K, Ohara O, Kunishima S, Ishiguro A. ETV6-related thrombocytopenia associated with a transient decrease in von Willebrand factor. Int J Hematol. 2021. Aug;114(2):297-300. doi: 10.1007/s12185-021-03136-4.
  5. Ishikawa T, Tamura E, Kasahara M, Uchida H, Higuchi M, Kobayashi H, Shimizu H, Ogawa E, Yotani N, Irie R, Kosaki R, Kosaki K, Uchiyama T , Onodera M, Kawai T. Severe Liver Disorder Following Liver Transplantation in STING-Associated Vasculopathy with Onset in Infancy. J Clin Immunol. 2021 Jul;41(5):967-974. doi: 10.1007/s10875-021-00977-w.
  6. Uchiyama T, Kawakami S, Masuda H, Yoshida K, Niizeki H, Mochizuki E, Edasawa K, Ishiguro A, Onodera M. A Distinct Feature of T Cell Subpopulations in a Patient with CHARGE Syndrome and Omenn Syndrome. J Clin Immunol 2021 Jan;41(1):233-237. doi: 10.1007/s10875-020-00875-7.
  7. Ohira M, Kikuchi E, Mizuta S, Yoshida N, Onodera M, Nakanishi M, Okuyama T, Mashima R. Production of therapeutic iduronate-2-sulfatase enzyme with a novel single-stranded RNA virus vector. Genes Cells 2021 Nov;26(11):891-904. doi: 10.1111/gtc.12894.
  8. Kataura T, Tashiro E, Nishikawa S, Shibahara K, Muraoka Y, Miura M, Sakai S, Katoh N, Totsuka M, Onodera M, Shin-Ya K, Miyamoto K, Sasazawa Y, Hattori N, Saiki S, Imoto M. A chemical genomics-aggrephagy integrated method studying functional analysis of autophagy inducers. Autophagy 2021 Aug;17(8):1856-1872. doi: 10.1080/15548627.2020.1794590.
  9. Nishizawa H, Matsumoto M, Chen G, Ishii Y, Tada K, Onodera M, Kato H, Muto A, Tanaka K, Igarashi K. Lipid peroxidation and the subsequent cell death transmitting from ferroptotic cells to neighboring cells. Cell Death 2021 Mar 29;12(4):332. doi: 10.1038/s41419-021-03613-y.
  10. Azami Y, Tsuyama N, Abe Y, Sugai-Takahashi M, Kudo KI, Ota A, Sivasundaram K, Muramatsu M, Shigemura T, Sasatani M, Hashimoto Y, Saji S, Kamiya K, Hanamura I, Ikezoe T, Onodera M, Sakai A. Chromosomal translocation t(11;14) and p53 deletion induced by the CRISPR/Cas9 system in normal B cell-derived iPS cells. Sci Rep 2021 Mar 4;11(1):5216. doi: 10.1038/s41598-021-84628-5.
  11. Matsukawa Y, Isshiki K, Osumi T, Fujiyama S, Fukushima H, Uchiyama T, Yamada M, Deguchi T, Imadome KI, Matsumoto K, Tomizawa D, Takada H, Onodera M, Kato M. Successful hematopoietic stem cell transplantation with reduced dose of busulfan for Omenn syndrome. Blood Cell Ther [in press]


  1. Takeuchi I, Kawai T, Nambu M, Migita O, Yoshimura S, Nishimura K, Yoshioka T, Ogura M, Kyodo R, Shimizu H, Ito S, Kato M, Onodera M, Hata K, Matsubara Y, Arai K. X-linked inhibitor of apoptosis protein deficiency complicated with Crohn's disease-like enterocolitis and Takayasu arteritis: A case report. Clin Immunol.2020 Aug;217:108495. doi: 10.1016/j.clim.2020.108495.
  2. Suzuki E, Kobori Y, Katsumi M, Ushijima K, Uchiyama T, Okada H, Miyado M, Fukami M. Copy-number Analysis of Y-linked Loci in Young Men with Non-Obstructive Azoospermia: Implications for the Rarity of Early Onset Mosaic Loss of Chromosome Y. Reprod Med Biol. 2020 Mar 2; 19(2):178-181. doi: 10.1002/rmb2.12321.
  3. Uchida H, Sakamoto S, Shimizu S, Takeda M, Yanagi Y, Fukuda A, Uchiyama T, Irie R, Kasahara M. Efficacy of Antithymocyte Globulin Treatment for Severe Centrilobular Injury Following Pediatric Liver Transplant: Clinical Significance of Monitoring Lymphocyte Subset. Exp Clin Transplant. 2020 Jun;18(3):325-333. doi: 10.6002/ect.2019.0387.
  4. 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. A prospective study of allogeneic hematopoietic stem cell transplantation with post-transplantation cyclophosphamide and anti-thymoglobulin from HLA-mismatched related donors for non-malignant diseases. Biol Blood Marrow Transplant, 2020 Nov; 26(11): e286-e291. doi: 10.1016/j.bbmt.2020.08.008.
  5. Yamaguchi T, Uchida E, Okada T, Ozawa K, Onodera M, Kume A, Shimada T, Takahashi S, Tani K, Nasu Y, Mashimo T, Mizuguchi H, Mitani K, Maki K. Aspects of gene therapy products using current genome-editing technology in Japan. Hum Gene Ther. 2020 Oct; 31(19-20):1043-1053. doi: 10.1089/hum.2020.156.
  6. Ishikawa T, Okai M, Mochizuki E, Uchiyama T, Onodera M, Kawai T. BCG infections at high frequency in both AR-CGD and X-CGD patients following BCG vaccination. Clin Infect Dis. 2020 Jul 27; ciaa 1049. doi: 10.1093/cid/ciaa1049.
  7. Oka Y, Hamada M, Nakazawa Y, Muramatsu H, Okuno Y, Higasa K, Shimada M, Takeshima H, Hanada K, Hirano T, Kawakita T, Sakaguchi H, Ichimura T, Ozono S, Yuge K, Watanabe Y, Kotani Y, Yamane M, Kasugai Y, Tanaka M, Suganami T, Nakada S, Mitsutake N, Hara Y, Kato K, Mizuno S, Miyake N, Kawai Y, Tokunaga K, Nagasaki M, Kito S, Isoyama K, Onodera M, Kaneko H, Matsumoto N, Matsuda F, Matsuo K, Takahashi Y, Mashimo T, Kojima S, Ogi T. Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and cause a multisystem disorder, AMeD syndrome. Sci Adv. 2020 Dec 18;6(51): eabd7197. doi: 10.1126/sciadv.abd7197.


  1. Kimura Y, Shofuda T, Higuchi Y, Nagamori I, Oda M, Nakamori M, Onodera M, Kanematsu D, Yamamoto A, Katsuma A, Suemizu H, Nakano T, Kanemura Y, Mochizuki H. Human Genomic Safe Harbors and the Suicide Gene-Based Safeguard System for iPSC-Based Cell Therapy. Stem Cells Transl Med. 2019 Mar 19. doi: 10.1002/sctm.18-0039.
  2. Narumoto S, Sakamoto S, Sasaki K, Hirata Y, Fukuda A, Uchiyama T, Irie R, Yoshida T, Kasahara M. ABO-incompatible liver transplantation for children under 2 years of age: A case report and a single-center review. Pediatr Transplant. 2019 23:e13308. doi: 10.1111/petr.13308.
  3. Tsuchida M, Kirino Y, Soejima Y, Onodera M, Arai K, Tamura E, Ishikawa T, Kawai T, Uchiyama T, Nomura S, Kobayashi D, Taguri M, Mitsuhashi T, Takata A, Miyake N, Nakajima H, Miyake S, Matsumoto N. Haploinsufficiency of A20 caused by a novel nonsense variant or entire deletion of TNFAIP3 is clinically distinct from Behçet disease. Arthritis Res Ther. 21: 137, 2019 doi: 10.1186/s13075-019-1928-5
  4. 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. 23:e13424. 2019 doi: 10.1111/petr.13424.
  5. Tomono T, Hirai Y, Chono H, Mineno J, Ishii A, Onodera M, Tamaoka A, Okada T. Infectivity Assessment of Recombinant Adeno-Associated Virus and Wild-Type Adeno-Associated Virus Exposed to Various Diluents and Environmental Conditions. Hum Gene Ther Methods. 30: 137-143, 2019.
  6. Kikuchi T, Nakae J, Kawano Y, Watanabe N, Onodera M, Itoh H. Foxo in T Cells Regulates Thermogenic Program through Ccr4/Ccl22. iScience. 22: 81-96, 2019.
  7. Ushijima K, Okuno M, Ayabe T, Kikuchi N, Kawamura T, Urakami T, Yokota I, Amemiya S, Uchiyama T, Kikuchi T, Ogata T, Sugihara S, Fukami M. Low prevalence of maternal microchimerism in peripheral blood of Japanese children with type I diabetes. Diabet Med. Doi: 1007/s12185-019-02795-8
  8. Shirai R, Osumi T, Terashima K, Kiyotani C, Uchiyama M, Tsujimoto S, Yoshida M, Yoshida K, Uchiyama T, Tmizawa D, Shioda Y, Sekiguchi M, Watanabe K, Keino D, Ueno-Yokohata H, Ohki K, Takita J, Ito S, Deguchi T, Kiyokawa N, Ogiwara H, Hishiki T, Ogawa S, Okita H, Matsumoto K, Yoshioka T, Kato M. High prevalence of SMARCB1 constitutional abnormalities including mosaicism in malignant rhabdoid tumours. Eur J Hum Genet 2020 Mar 26. doi: 10.1038/s41431-020-0614-z.
  9. Saito T, Ito Y, Samura O, Aoki H, Uchiyama T, Okamoto A, Hata K. Direct assessment of a single-cell DNA using crudely purified live cells: a proof of concept for noninvasive prenatal definitive diagnosis. J Mol Diagn. 22: 132-140, 2020. doi: 10.1016/j.jmoldx.2019.10.006.
  10. Tsujimoto SI, Shirai R, Utano T, Osumi T, Matsumoto K, Shioda Y, Kiyotani C, Uchiyama T, Deguchi T, Terashima K, Tomizawa D, Matsumoto K, Kato M. Comparison of clonazepam and levetiracetam in children for prevention of busulfan-induced seizure in hematopoietic stem cell transplantation. Int J Hematol. 111: 463-466, 2020.
  11. Ushijima K, Okuno M, Ayabe T, Kikuchi N, Kawamura T, Urakami T, Yokota I, Amemiya S, Uchiyama T, Kikuchi T, Ogata T, Sugihara S, Fukami M; Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes. Low prevalence of maternal microchimerism in peripheral blood of Japanese children with type 1 diabetes. Diabet Med. 2019 Dec 23: doi: 10.1111/dme.14221.


  1. Kamei K, Miyairi I, Ishikura K, Ogura M, Shoji K, Funaki T, Ito R, Arai K, Abe J, Kawai T, Onodera M, Ito S. Prospective Study of Live Attenuated Vaccines for Patients with Nephrotic Syndrome Receiving Immunosuppressive Agents. J Pediatr, S0022-3476 (17) 31756-0, 2018.
  2. Nishi K, Kawai T, Kubota M, Ishiguro A, Onodera M. X-linked agammaglobulinemia complicated with pulmonary aspergillosis. Pediatr Int 1: 90-92, 2018.
  3. Osumi T, Tsujimoto S, Nakabayashi K, Taniguchi M, Shirai R, Yoshida M, Uchiyama T, Nagasawa J, Goyama S, Yoshida T, Tomizawa T, Kurokawa M, Matsubara Y, Kiyokawa N, Hata K, Kato M. Somatic MECOM mosaicism in a patient with congenital bone marrow failure without a radial abnormality. Pediatr Blood Cancer. 65: e26959, 2018
  4. Tsujimoto S, Osumi T, Uchiyama M, Shirai R, Moriyama T, Nishii R, Yamada Y, Kudo K, Sekiguchi M, Arakawa Y, Yoshida M, Uchiyama T, KTerui, Ito S, Koh K, Takita J, Ito E, Tomizawa D, Manabe A, Kiyokawa N, Yang J, Kato M. Diplotype analysis of NUDT15 variants and 6-mercaptopurine sensitivity in pediatric lymphoid neoplasms. Leukemia. 32: 2710-2714, 2018.
  5. Okano T, Imai K, Uchiyama T, Morio T. Hematopoietic stem cell transplantation for progressive combined immunodeficiency and lymphoproliferation in Activated PI3Kd syndrome type 1. J Allergy Clin Immunol. 2018 (in press)
  6. Osumi T, Tsujimoto S, Tamura M, Uchiyama M, Nakabayashi K, Okamura K, Toshida M, Tomizawa D, Watanabe A, Takahashi H, Hori T, Yamamoto S, Hamamoto K, Migita M, Ogata-Kawata H, Uchiyama T, Kizawa H, Ueno-Yokohata H, Shirai R, Seki M, Ohki K, Inukai T, Ogawa S, Kitamura T, Matsumoto K, Hata K, Kiyokawa N, Goyama S, Kato M. Recurrent RARB translocation in Acute Promyelocytic leukemia lacking RARA translocation. Cancer Res. 78: 4452-4458, 2018
  7. 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. 018 Jun 29. doi: 10.1038/s41409-018-0271-9
  8. Shoji K, Kawai T, Onodera M, Tsutsumi Y, Nosaka S, Miyairi I. Multiple osteolytic lesions on the skull of a girl with Mendelian susceptibility to mycobacterial disease. Pediatr Int. 60: 1043-1044, 2018.
  9. Tomono T, Hirai Y, Okada H, Miyagawa Y, Adachi K, Sakamoto S, Kawano Y, Chono H, Mineno J, Ishii A, Shimada T, Onodera M, Tamaoka A, Okada T. Highly Efficient Ultracentrifugation-free Chromatographic Purification of Recombinant AAV Serotype 9. Mol Ther Methods Clin Dev. 11: 180-190, 2018. 32:2710-2714, 2018
  10. Tsujimoto S, Osumi T, Uchiyama M, Shirai R, Moriyama T, Nishii R, Yamada Y, Kudo Km Sekiguchi M, Arakawa Y, Yoshida M, Uchiyama T, Terui K, Ito S, Koh K, Takita J, Tomizawa D, Manabe A, Kiyokawa N, N. Yang JJ, Kato M. Diplotype analysis of NUD15 variants and 6-mercaptopurine sensitivity in pediatric lymphoid neoplasms. Leukemia, 32:2710-2714, 2018
  11. Narumoto S, Sakamoto S, Sasaki K, Hirata Y, Fukuda A, Uchiyama T, Irie R, Yoshioka T, Kasahara M. ABO-incompatible liver transplantation for children under 2 years of age: A case report and a single center review. Pediatr. Transplant. Doi: 10.1111/petr.13308. 2018


  1. Okuno M, Kasahara Y, Onodera M, Takubo N, Okajima M, Suga S, Watanabe N, Suzuki J, Ayabe T, Urakami T, Kawamura T, Kikuchi N, Yokota I, Kikuchi T, Amemiya S, Nakabayashi K, Hayashi K, Hata K, Matsubara Y, Ogata T, *Fukami M, Sugihara S. Nucleotide substitutions in CD101, the human homolog of a diabetes susceptibility gene in non-obese diabetic mouse, in patients with type 1 diabetes. Journal of Diabetes Investigation 8: 286-294, 2017.
  2. Osumi T, Kato M. Ouchi-Uchiyama M, Tomizawa D, Kataoka K, Fuji Y, Seki M, TAkita J, Ogawa S, Uchiyama T, Ohki K, Kiyokawa N. Blastic transformation of juvenile myelomonocytic leukemia caused by the copy number gain of onocogenic KRAS. Pediatr Blood Cancer 2017 doi: 10.1002/pbc.26496
  3. Goto F, Uchiyama T, Nakazawa Y, Kawai T, Imai K, Onodera M. Persistent impairment of T cell regeneration in a patient with activated PI3K d syndrome. J Clin Immunol. 2017 doi: 10.1007/s10875-017-0393-7