東京慈恵医科大学 総合医科研究センター遺伝子治療研究部
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主な競争的研究費

平成30年度日本医療研究開発機構研究費 難治性疾患実用化研究事業
(代表)大橋十也 ムコ多糖II型の造血幹細胞を標的とした遺伝子治療法の実用化研究

平成30年度文部科学省 科学研究費助成事業 基盤研究(B)
(代表)大橋十也 GM1ガングリオシドーシスの造血幹細胞を標的とした遺伝子治療法の開発

平成30年度文部科学省 科学研究費助成事業 基盤研究(C)
(代表)小林博司 人工知能・次世代シークエンサーを用いたファブリー病の統合データーベース構築

平成30年度文部科学省 科学研究費助成事業 基盤研究(C)
(代表)小林博司 iPS細胞及び遺伝子改変システムを用いたムコ多糖症等の治療用デバイス作成

平成30年度東京大学医科学研究所共同研究 先端医療研究開発共同研究領域
(代表)大橋十也 ムコ多糖II型の造血幹細胞を標的とした遺伝子治療法の前臨床試験

平成30年度日本医療研究開発機構研究費 難治性疾患実用化研究事業
(分担)大橋十也 小児神経疾患・先天代謝異常症に対する遺伝子治療法開発

平成30年度厚生労働科学研究費補助金 難治性疾患等政策研究事業
(分担)大橋十也、小林博司、ライソゾーム病(ファブリ病含む)に関する調査研究

平成30年度 日本学術振興会 海外特別研究員

佐藤洋平  速やかに臨床応用が可能な制御性T細胞による免疫制御法の研究基盤創出
2018

•Kobayashi H, Ariga M, Sato Y, Fujiwara M, Fukasawa N, Fukuda T, Takahashi H, Ikegami M, Kosuga M, Okuyama T, Eto Y, Ida H. P-Tau and Subunit c Mitochondrial ATP Synthase Accumulation in the Central Nervous System of a Woman with Hurler-Scheie Syndrome Treated with Enzyme Replacement Therapy for 12 Years. JIMD Rep. 2018;41:101-107.

•Sugano H, Shirai Y, Horiuchi T, Saito N, Shimada Y, Eto K, Uwagawa T, Ohashi T, Yanaga K.  Nafamostat Mesilate Enhances the Radiosensitivity and Reduces the Radiation-Induced Invasive Ability of Colorectal Cancer Cells. Cancers (Basel). 2018 Oct 17;10(10). pii: E386.

•Sakurai K, Ohashi T, Shimozawa N, Seo JH, Okuyama T, Ida H.  Characteristics of Japanese patients with X-linked adrenoleukodystrophy and concerns of their families from the 1st registry system. Brain Dev. 2018 Aug 1. pii: S0387-7604(18)30332-2.

•Haruki K, Shiba H, Shimada Y, Shirai Y, Iwase R, Fujiwara Y, Uwagawa T, Ohashi T, Yanaga K. Glycogen synthase kinase-3β activity plays a key role in the antitumor effect of nafamostat mesilate in pancreatic cancer cells. Ann Gastroenterol Surg. 2017 Aug;2(1):65-71.

•Hongo K, Ito K, Date T, Anan I, Inoue Y, Morimoto S, Ogawa K, Kawai M, Kobayashi H, Kobayashi M, Ida H, Ohashi T, Taniguchi I, Yoshimura M, Eto Y. The beneficial effects of long-term enzyme replacement therapy on cardiac involvement in Japanese Fabry patients. Mol Genet Metab 2018;124:143-151.

•Saito N, Shirai Y, Uwagawa T, Horiuchi T, Sugano H, Haruki K, Shiba H, Ohashi T, Yanaga K.  Pomalidomide enhanced gemcitabine and nab-paclitaxel on pancreatic cancer both in vitro and in vivo. Oncotarget. 2018 Mar;9(21):15780-15791.

•Shirai Y, Saito N, Uwagawa T, Shiba H, Horiuchi T, Iwase R, Haruki K, Ohashi T, Yanaga K.  Pomalidomide promotes chemosensitization of pancreatic cancer by inhibition of NF-κB.  Oncotarget. 2018 Feb;9(20):15292-15301.

•Hoshina H, Shimada Y, Higuchi T, Kobayashi H, Ida H, Ohashi T.  Chaperone effect of sulfated disaccharide from heparin on mutant iduronate-2-sulfatase in mucopolysaccharidosis type II.  Mol Genet Metab. 2018 Feb;123(2):118-122.

2017

•Sato Y, Kobayashi H, Higuchi T, Shimada Y, Ida H, Ohashi T. Metabolomic Profiling of Pompe Disease-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Reveals That Oxidative Stress Is Associated with Cardiac and Skeletal Muscle Pathology.  Stem Cells Transl Med. 2017 Jan;6(1):31-39.

•Sato Y, Ida H, Ohashi T. Anti-BlyS antibody reduces the immune reaction against enzyme and enhances the efficacy of enzyme replacement therapy in Fabry disease model mice. Clin Immunol. 2017 May;178:56-63.

•Shirai Y, Uwagawa T, Shiba H, Shimada Y, Horiuchi T, Saito N, Furukawa K, Ohashi T, Yanaga K. Recombinant thrombomodulin suppresses tumor growth of pancreatic cancer by blocking thrombin-induced PAR1 and NF-κB activation.  Surgery. 2017 Jun;161(6):1675-1682.

•Hughes DA, Nicholls K, Shankar SP, Sunder-Plassmann G, Koeller D, Nedd K, Vockley G, Hamazaki T, Lachmann R, Ohashi T, Olivotto I, Sakai N, Deegan P, Dimmock D, Eyskens F, Germain DP, Goker-Alpan O, Hachulla E, Jovanovic A, Lourenco CM, Narita I, Thomas M, Wilcox WR, Bichet DG, Schiffmann R, Ludington E, Viereck C, Kirk J, Yu J, Johnson F, Boudes P, Benjamin ER, Lockhart DJ, Barlow C, Skuban N, Castelli JP, Barth J, Feldt-Rasmussen U. Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study. J Med Genet 2017;54:288-296.

2016

•Kopajtich R, Murayama K, Janecke AR, Haack TB, Breuer M, Knisely AS, Harting I, Ohashi T, Okazaki Y, Watanabe D, Tokuzawa Y, Kotzaeridou U, Kolker S, Sauer S, Carl M, Straub S, Entenmann A, Gizewski E, Feichtinger RG, Mayr JA, Lackner K, Strom TM, Meitinger T, Muller T, Ohtake A, Hoffmann GF, Prokisch H, Staufner C. Biallelic IARS Mutations Cause Growth Retardation with Prenatal Onset, Intellectual Disability, Muscular Hypotonia, and Infantile Hepatopathy. Am J Hum Genet 2016 Aug;99:414-422.

•Kono Y, Wakabayashi T, Kobayashi M, Ohashi T, Eto Y, Ida H, et al. Characteristics of Cerebral Microbleeds in Patients with Fabry Disease. J Stroke Cerebrovasc Dis 2016;25:1320-1325.

•Higuchi T, Kobayashi M, Ogata J, Kaneshiro E, Shimada Y, Kobayashi H, Eto Y, Maeda S, Ohtake A, Ida H, Ohashi T. Identification of Cryptic Novel alpha-Galactosidase A Gene Mutations: Abnormal mRNA Splicing and Large Deletions. JIMD Rep 2016;30:63-72.

•Shirai Y, Shiba H, Iwase R, Haruki K, Fujiwara Y, Furukawa K, Uwagawa T, Ohashi T, Yanaga K. Dual inhibition of nuclear factor kappa-B and Mdm2 enhance the antitumor effect of radiation therapy for pancreatic cancer. Cancer Lett 2016 28;370:177-184.

•Shimada Y, Wakabayashi T, Akiyama K, Hoshina H, Higuchi T, Kobayashi H, Eto Y, Ida H, Ohashi T. A method for measuring disease-specific iduronic acid from the non-reducing end of glycosaminoglycan in mucopolysaccharidosis type II mice. Mol Genet Metab 2016;117:140-143.

•Limkul J, Iizuka S, Sato Y, Misaki R, Ohashi T, et al. The production of human glucocerebrosidase in glyco-engineered Nicotiana benthamiana plants. Plant Biotechnol J 2016;14:1682-1694.

•Ishiyama H, Satoh T, Yorozu A, Saito S, Kataoka M, Hashine K, Nakamura R, Tanji S, Masui K, Okihara K, Ohashi T, Momma T, Aoki M, Miki K, Kato M, Morita M, Katayama N, Nasu Y, Kawanaka T, Fukumori T, Ito F, Shiroki R, Baba Y, Inadome A, Yoshioka Y, Takayama H, Hayakawa K. Multi-institutional retrospective analysis of learning curves on dosimetry and operation time before and after introduction of intraoperatively built custom-linked seeds in prostate brachytherapy. J Radiat Res 2016;57:68-74.

•Horiuchi T, Uwagawa T, Shirai Y, Saito N, Iwase R, Haruki K, Shiba H, Ohashi T, Yanaga K. New treatment strategy with nuclear factor-kappaB inhibitor for pancreatic cancer. J Surg Res 2016;206:1-8.

•Kato S, Yabe H, Takakura H, Mugishima H, Ishige M, Tanaka A, Kato K, Yoshida N, Adachi S, Sakai N, Hashii Y, Ohashi T, Sasahara Y, Suzuki Y, Tabuchi K. Hematopoietic stem cell transplantation for inborn errors of metabolism: A report from the Research Committee on Transplantation for Inborn Errors of Metabolism of the Japanese Ministry of Health, Labour and Welfare and the Working Group of the Japan Society for Hematopoietic Cell Transplantation. Pediatr Transplant 2016;20:203-214.

•Yokoi T, Yokoi K, Akiyama K, Higuchi T, Shimada Y, Kobayashi H, Sato T, Ohteki T, Otsu M, Nakauchi H, Ida H, Ohashi T. Non-myeloablative preconditioning with ACK2 (anti-c-kit antibody) is efficient in bone marrow transplantation for murine models of mucopolysaccharidosis type II. Mol Genet Metab 2016;119:232-238.

•Sato Y, Kobayashi H, Higuchi T, Shimada Y, Ida H, Ohashi T. TFEB overexpression promotes glycogen clearance of Pompe disease iPSC-derived skeletal muscle. Mol Ther Methods Clin Dev 2016 10;3:16054.

•Kono Y, Wakabayashi T, Kobayashi M, Ohashi T, Eto Y, Ida H, et al. Characteristics of Cerebral Microbleeds in Patients with Fabry Disease. J Stroke Cerebrovasc Dis 2016;25:1320-1325.

•Saito O, Kusano E, Akimoto T, Asano Y, Kitagawa T, Suzuki K, Ishige N, Akiba T, Saito A, Ishimura E, Hattori M, Hishida A, Guili C, Maruyama H, Kobayashi M, Ohashi T, Matsuda I, Eto Y. Prevalence of Fabry disease in dialysis patients: Japan Fabry disease screening study (J-FAST). Clin Exp Nephrol. 2016;20:284-293.

•Shirai Y, Shiba H, Iwase R, Haruki K, Fujiwara Y, Furukawa K, Uwagawa T, Ohashi T, Yanaga K. Dual inhibition of nuclear factor kappa-B and Mdm2 enhance the antitumor effect of radiation therapy for pancreatic cancer. Cancer Lett. 2016 Jan 28;370(2):177-84. 

2015

•Nakano S, Tsukimura T, Togawa T, Ohashi T, Kobayashi M, Takayama K, Kobayashi Y, Abiko H, Satou M, Nakahata T, Warnock DG, Sakuraba H, Shibasaki F. Rapid Immunochromatographic Detection of Serum Anti-α-Galactosidase A Antibodies in Fabry Patients after Enzyme Replacement Therapy. PLoS One. 2015 Jun 17;10(6):e0128351.

•Shimada Y, Wakabayashi T, Akiyama K, Hoshina H, Higuchi T, Kobayashi H, Eto Y, Ida H,Ohashi T. A method for measuring disease-specific iduronic acid from the non-reducing end of glycosaminoglycan in mucopolysaccharidosis type II mice. Mol Genet Metab. 2015 May 21. pii: S1096-7192(15)30008-1.

•Wakabayashi T, Shimada Y, Akiyama K, Higuchi T, Fukuda T, Kobayashi H, Eto Y, Ida H, Ohashi T.  Hematopoietic Stem Cell Gene Therapy Corrects Neuropathic Phenotype in Murine Model of Mucopolysaccharidosis Type II.  Hum Gene Ther. 2015 Apr 20.

•Yokoi K, Akiyama K, Kaneshiro E, Higuchi T, Shimada Y, Kobayashi H, Akiyama M, Otsu M, Nakauchi H, Ohashi T, Ida H.  Effect of donor chimerism to reduce the level of glycosaminoglycans following bone marrow transplantation in a murine model of mucopolysaccharidosis type II.  J Inherit Metab Dis. 2015 Mar;38(2):333-40.

•Shimada Y, Nishimura E, Hoshina H, Kobayashi H, Higuchi T, Eto Y, Ida H, Ohashi T.  Proteasome Inhibitor Bortezomib Enhances the Activity of Multiple Mutant Forms of Lysosomal α-Glucosidase in Pompe Disease. JIMD Rep. 2015;18:33-9.

•Sato Y, Kobayashi H, Higuchi T, Shimada Y, Era T, Kimura S, Eto Y, Ida H, Ohashi T. Disease modeling and lentiviral gene transfer in patient-specific induced pluripotent stem cells from late-onset Pompe disease patient. Mol Ther Methods Clin Dev. 2015 Jul 8;2:15023.

2014

•Sato Y, Kobayashi H, Sato S, Shimada Y, Fukuda T, Eto Y, Ohashi T, Ida H. Systemic accumulation of undigested lysosomal metabolites in an autopsy case of mucolipidosis type II; autophagic dysfunction in cardiomyocyte.  Mol Genet Metab. 2014 Jul;112(3):224-8.

•Higuchi T, Kawagoe S, Otsu M, Shimada Y, Kobayashi H, Hirayama R, Eto K, Ida H, Ohashi T, Nakauchi H, Eto Y. The generation of induced pluripotent stem cells (iPSCs) from patients with infantile and late-onset types of Pompe disease and the effects of treatment with acid-α-glucosidase in Pompe's iPSCs. Mol Genet Metab. 2014 May;112(1):44-8.

•Akiyama K, Shimada Y, Higuchi T, Ohtsu M, Nakauchi H, Kobayashi H, Fukuda T, Ida H, Eto Y, Crawford BE, Brown JR, Ohashi T. Enzyme augmentation therapy enhances the therapeutic efficacy of bone marrow transplantation in mucopolysaccharidosis type II mice. Mol Genet Metab. 2014 Feb;111(2):139-46.

 

2013

•Iwase R, Haruki K, Fujiwara Y, Furukawa K, Shiba H, Uwagawa T, Misawa T, Ohashi T, Yanaga K.Combination chemotherapy of nafamostat mesylate with gemcitabine for gallbladder cancer targeting nuclear factor-κB activation. J Surg Res. 2013 Sep;184(1):605-12.

•Haruki K, Shiba H, Fujiwara Y, Furukawa K, Iwase R, Uwagawa T, Misawa T, Ohashi T, Yanaga K. Inhibition of nuclear factor-κB enhances the antitumor effect of tumor necrosis factor-α gene therapy for hepatocellular carcinoma in mice. Surgery. 2013 Sep;154(3):468-78.

•Haruki K, Shiba H, Fujiwara Y, Furukawa K, Iwase R, Uwagawa T, Misawa T, Ohashi T, Yanaga K. Inhibition of nuclear factor-κB enhances the antitumor effect of paclitaxel against gastric cancer with peritoneal dissemination in mice. Dig Dis Sci. 2013 Jan;58(1):123-31.

•Sato T, Ikeda M, Yotsumoto S, Shimada Y, Higuchi T, Kobayashi H, Fukuda T, Ohashi T, Suda T, Ohteki T. Novel interferon-based pre-transplantation conditioning in the treatment of a congenital metabolic disorder. Blood. 2013 Apr 18;121(16):3267-73.

•Furukawa K, Uwagawa T, Haruki K, Fujiwara Y, Iida T, Shiba H, Misawa T, Ohashi T, Yanaga K. Nuclear factor κB activity correlates with the progression and prognosis of pancreatic cancer in a mouse model. Surg Today. 2013 Feb;43(2):171-7.

•Fujiwara Y, Shiba H, Iwase R, Haruki K, Furukawa K, Uwagawa T, Misawa T, Ohashi T, Yanaga K.  Inhibition of nuclear factor kappa-B enhances the antitumor effect of combination treatment with tumor necrosis factor-alpha gene therapy and gemcitabine for pancreatic cancer in mice. J Am Coll Surg. 2013 Feb;216(2):320-32.

 

2012

•Nishiyama Y, Shimada Y, Yokoi T, Kobayashi H, Higuchi T, Eto Y, Ida H, Ohashi T. Akt inactivation induces endoplasmic reticulum stress-independent autophagy in fibroblasts from patients with Pompe disease. Mol Genet Metab. 2012 Nov;107(3):490-5.

• Ohashi T, Iizuka S, Shimada Y, Higuchi T, Eto Y, Ida H, Kobayashi H. Administration of Anti-CD3 Antibodies Modulates the Immune Response to an Infusion of α-glucosidase in Mice. Mol Ther. 2012 Oct;20(10):1924-31.

• Haruki K, Shiba H, Fujiwara Y, Furukawa K, Wakiyama S, Ogawa M, Ishida Y, Misawa T, Yanaga K. Perioperative change in peripheral blood monocyte count may predict prognosis in patients with colorectal liver metastasis after hepatic resection. J Surg Oncol. 2012;106(1):31-5.

• Higuchi T, Shimizu H, Fukuda T, Kawagoe S, Matsumoto J, Shimada Y, Kobayashi H, Ida H, Ohashi T, Morimoto H, Hirato T, Nishino K, Eto Y. Enzyme replacement therapy (ERT) procedure for mucopolysaccharidosis type II (MPS II) by intraventricular administration (IVA) in murine MPS II. Mol Genet Metab. 2012;107(1-2):122-8.

2011

•Ohashi T, Iizuka S, Shimada Y, Eto Y, Ida H, Hachimura S, Kobayashi H. Oral administration of recombinant human acid α-glucosidase reduces specific antibody formation against enzyme in mouse. Mol Genet Metab. 2011;103(1):98-100.

•Yokoi T, Kobayashi H, Shimada Y, Eto Y, Ishige N, Kitagawa T, Otsu M, Nakauchi H, Ida H, Ohashi T. Minimum requirement of donor cells to reduce the glycolipid storage following bone marrow transplantation in a murine model of Fabry disease.J Gene Med. 2011;13(5):262-8.

•Fujiwara Y, Furukawa K, Shimada Y, Iida T, Shiba H, Uwagawa T, Misawa T, Ohashi T, Yanaga K. Combination paclitaxel and inhibitor of nuclear factor κB activation improves therapeutic outcome for model mice with peritoneal dissemination of pancreatic cancer. Pancreas. 2011;40(4):600-7.

•Furukawa K, Ohashi T, Haruki K, Fujiwara Y, Iida T, Shiba H, Uwagawa T, Kobayashi H, Yanaga K. Combination treatment using adenovirus vector-mediated tumor necrosis factor-alpha gene transfer and a NF-κB inhibitor for pancreatic cancer in mice. Cancer Lett. 2011;306(1):92-8.

•Fujiwara Y, Furukawa K, Haruki K, Shimada Y, Iida T, Shiba H, Uwagawa T, Ohashi T, Yanaga K. Nafamostat mesilate can prevent adhesion, invasion and peritoneal dissemination of pancreatic cancer thorough nuclear factor kappa-B inhibition. J Hepatobiliary Pancreat Sci. 2011;18(5):731-9.

•Matsumoto K, Yokoo T, Yokote S, Utsunomiya Y, Ohashi T, Hosoya T. Functional development of a transplanted embryonic kidney: effect of transplantation site. J Nephrol. 2011 Apr 13.pii: 4C3C9744-4467-4DC9-8E85-5BFCF7AC0BA7. doi: 10.5301/JN.2011.7426

•Kawagoe S, Higuchi T, Meng XL, Shimada Y, Shimizu H, Hirayama R, Fukuda T,Chang H, Nakahata T, Fukada SI, Ida H, Kobayashi H, Ohashi T, Eto Y. Generation of induced pluripotent stem (iPS) cells derived from a murine model of Pompe disease and differentiation of Pompe-iPS cells into skeletal muscle cells. Mol Genet Metab. 2011;104(1-2):123-8.

•Shimada Y, Kobayashi H, Kawagoe S, Aoki K, Kaneshiro E, Shimizu H, Eto Y, Ida H, Ohashi T. Endoplasmic reticulum stress induces autophagy through activation of p38 MAPK in fibroblasts from Pompe disease patients carrying c.546 G> T mutation.
Mol Genet Metab. 2011;104(4):566-73.

•Shimada Y, Nishida H, Nishiyama Y, Kobayashi H, Higuchi T, Eto Y, Ida H, Ohashi T.Proteasome inhibitors improve the function of mutant lysosomal alpha-glucosidase in fibroblasts from Pompe disease patient carrying c.546G>T mutation.Biochem. Biophys. Res. Commun., 2011;415(2):274-8.

•Kobayashi H, Shimada Y, Ikegami M, Kawai T, Sakurai K, Urashima T, IjimaM,Fujiwara M, Kaneshiro E, Ohashi T, Eto Y, Ishigaki K, Osawa M, Kyosen SO, IdaH. Pathology of the first autopsy case diagnosed as mucolipidosis type III alpha/beta suggesting autophagic dysfunction.Mol Genet Metab.2011;102(2):170-5.

2010

•Kobayashi H, Shimada Y, Ikegami M, Kawai T, Sakurai K, Urashima T, Ijima M, Fujiwara M, Kaneshiro E, Ohashi T, Eto Y, Ishigaki K, Osawa M, Kyosen SO, Ida H. Pathology of the first autopsy case diagnosed as mucolipidosis type III alpha/beta suggesting autophagic dysfunction..  Mol Genet Metab. 2010 May;100(1):14-9.

•Furukawa K, Iida T, Shiba H, Fujiwara Y, Uwagawa T, Shimada Y, Misawa T, Oha shi T, Yanaga K. Anti-tumor effect by inhixbition of NF-κB activation using nafamostat mesilate for pancreatic cancer in a mouse model. Oncol Rep.2010;24: 843-850.

•Kobayashi H, Shimada Y, Ikegami M, Kawai T, Sakurai k, Urashima T, Iijima M, Fujiwara M, Kaneshiro E, Ohashi T, Eto Y, Ishigaki K, Osawa M, Kyosen OS, Ida H. Prognostic factors for the Late Onset Pompe Disease with Enzyme Replacement Therapy: From Our Experience of 4 cases including an autopsy case. Mol Genet Metab. 2010;100(1):14-9.

• Tajima A, Ohashi T, Hamano S, Higurashi N, Ida H. Gaucher Disease Patient With Myoclonus Epilepsy and a Novel Mutation. Pediatr Neurol 2010;42:65-68.

• Fujiwara Y, Shiba H, Furukawa K, Iida T, Haruki K, Gocho T, Wakiyama S, Hirohara S, Ishida Y, Misawa T, Ohashi T, Yanaga K. Glasgow prognostic score is related to blood transfusion requirements and post-operative complications in hepatic resection for hepatocellular carcinoma. Anticancer Res. 2010 Dec;30(12):5129-36.

•Fujiwara Y, Shiba H, Furukawa K, Iida T, Sakamoto T, Gocho T, Wakiyama S, Hirohara S, Ishida Y, Misawa T, Ohashi T, Yanaga K. Perioperative change in white blood cell count predicts outcome of hepatic resection for hepatocellular carcinoma. J Hepatobiliary Pancreat Sci. 2010 Nov;17(6):892-7.


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