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  2. Research Institute
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  4. Department of Pathophysiology of Heart Failure and Therapeutics
  5. Mariko HARADA-SHIBA

Research Institute

Mariko HARADA-SHIBA

Name Mariko HARADA-SHIBA
Department Name,
Job Title		 Director, Department of Molecular Innovation in Lipidolpogy
Tel +81-6-6833-5012 (ext. 8209)
FAX +81-6-6872-8415
E-Mail Mshiba☆ri.ncvc.go.jp　　　　　　　　☆＝@
Research Field Lipidology, Gene therapy, Molecular biology
Research Result
  • Yamamoto T, Obika S, Nakatani M, Yasuhara H, Wada F, Shibata E, Shibata MA, Harada-Shiba M: Locked nucleic acid antisense inhibitor targeting apolipoprotein C-III efficiently and preferentially removed triglyceride from large VLDL particles from murine plasma, European Journal of Pharmacology, in press
  • Teramoto T, Sasaki J, Harada-Shiba M, Arai H, Ishibasi S, Birou S, Bujo H, Daida H, Dohi S, Egusa G, Hiro T, Hirobe K, Iida M, Kihara S, Kinoshita M, Maruyama C, Nohara A, Ohta T, Oikawa S, Okada T, Okamura T, Watatsuki A, Yamashita S, Yokode M, YOkote K: Familial hypercholesterolemia, Executive summary of the Japan Atherosclerosis Society(JAS) Guidelines for diagnosis and prevention of atherosclerotic cardiovascular diseases in Japan-2012 version, J Atheroscler Thromb, in press
  • Nagasaki Y, Yamazaki T, Kikuchi A, Harada-Shiba M: Elevated atherogenic indexfollowing oral administration of quaternized polyamine nanogels, Colloids and Surfaces, in press
  • Shibata MA, Shibata E, Morimoto J, Harada-Shiba M, Therapy with siRNA for Vegf-c but Not for Vegf-d Suppresses Wide-spectrum Organ Metastasis in an Immunocompetent Xenograft Model of Metastatic Mammary Cancer, Anticancer Research, 2013; 33: 4237-4248.
  • Yokoyama S, Ueshima H, Miida T, Nakamura M, Takata K, Fukukawa T, Goto T, Harada-Shiba M, Sano M, Kato K, Matsuda K: High-density lipoprotein of Japanese has markedly increased over the past twenty years, J Atheroscler Thromb, in press
  • Kobayashi K, Nagata E, Sasaki K, Harada-Shiba M, Kojo S, Kikuzaki H: Increase in Secretory Sphingomyelinase Activity and Specific Ceramides in the Aorta of Apolipoprotein E Knockout Mice during Aging, Biol. Pharm. Bull, 2013; 36(7): 1192-1196.
  • Yuasa Y, Osaki T, Makino H, Iwamoto N, Kishimoto I, Usami M, Harada-Shiba M: Proeomic analysis of proteins eliminated by LDL-apheresis, Ther Apher Dial, in press
  • Makino H, Harada-Shiba M: New aspects of statin therapy, IEMAMC, 2013; 13: 97-106.
  • Terasaki F, Morita H, Harada-Shiba M, Ohta N, Otsuka K, Nogi S, Miyamura M, Suzuki S, Ito T, Shimomura H, Katsumata T, Miyamoto Y, Ishizaka N: Familial Hypercholesterolemia with Multiple Large Tendinous Xanthomas and Advanced coronary Artery Atherosclerosis: Intern Med, 2013; 52: 577-581.
  • Shibata MA, Ambati J, Shibata E, Yoshidome K, Harada-Shiba M: Mammary cancer gene therapy targeting lymphangiogenesis:VEGF-C siRNA and soluble VEGF receptor-s, a splicing variant, Med Mol Morphlo, 2012; 45: 179-184.
  • Kang JH, Tachibana Y, Obika S, Harada-Shiba M, Yamaoka T: Efficient reduction of serum cholesterol by combining a liver-targeted gene delivery system with chemically modified apolipoprotein B siRNA: J Control Release, 2012; 163(2): 119-124.
  • Yamamoto T, Yasuhara H, Wada F, Harada-Shiba M, Imanishi T, Obika S: Superior silencing by 2',4'-BNANC-based short antisense oligonucleotides compared to 2',4'-BNA/LNA-based apolipoprotein B antisense inhibitors: J Nucleic Acids, 2012; 707323.
  • Harada-Shiba M, Arai H, Oikawa S, Ohta T, Okada T, Okamura T, Nohara A, Bujo H, Yokote K, Wakatsuki A, Ishibashi S, Yamashita S: Guidelines for the management of familial hypercholesterolemia: J Atheroscler Thromb, 2012; 19(12): 1043-1060.
  • Harada-Shiba M, Arai H, Okamura T, Yokote K, Oikawa S, Nohara A, Okada T, Ohta T, Bujo H, Watanabe M, Wakatsuki A, Yamashita S: Multicenter study to determine the diagnosis criteria of heterozygous familial hypercholesterolemia in Japan: J Atheroscler Thromb, 2012; 19(11): 1019-1026.
  • Wada S, Obika S, Shibata MA, Yamamoto T, Nakatani M, Yamaoka T, Torigoe H, Harada-Shiba M: Development of a 2',4'-BNA/LNA based siRNA for dyslipidemia and assessment of the effects of its chemical modifications in vivo: Molecular Therapy - Nucleic Acids, 2012; 1, e45: 1-15.
  • Yamamoto T, Harada-Shiba M, Nakatani M, Wada S, Yasuhara H, Narukawa K, Sasaki K, Shibata MA, Torigoe H, Yamaoka T, Imanishi T, Obika S: Cholesterol-Lowering Action of BNA-based Antisense Oligonucleotides Targeting PCSK9 in Atherogenic Diet-Induced Hypercholesterolemic Mice: Molecular Therapy- Nucleic Acid, 2012; 1, e22: 1-11.
  • Uchida S, Itaka K, Chen Q, Osada K, Ishii T, Shibata MA, Harada-Shiba M, Kataoka K: PEGylated polyplex with optimized PEG shielding enhances gene introduction in lungs by minimizing inflammatory responses: Mol Ther, 2012; 20(6): 1196-1203.
  • Sugisawa T, Okamura T, Makino H, Watanabe M, Kishimoto I, Miyamoto Y, Iwamoto N, Yamamoto A, Yokoyama S, Harada-Shiba M: Defining patients at extremely high risk for coronary artery disease in heterozygous familial hypercholesterolemia. J Atheroscler Thromb, 2012; 19(4) : 369-375.
  • Yokoyama S, Yamashita S, Ishibashi S, Sone H, Oikawa S, Shirai K, Ohta T, Bujo H, Kobayashi J, Arai H, Harada-Shiba M, Eto M, Hayashi T, Gotoda T, Suzuki H, Yamada N: Background to discuss guidelines for control of plasma HDL-cholesterol in Japan. J Atheroscler Thromb, 2012; 19(3): 207-212.
  • Gotoda T, Shirai K, Ohta T, Kobayashi J, Yokoyama S, Oikawa S, Bujo H, Ishibashi S, Arai H, Yamashita S, Harada-Shiba M, Eto M, Hayashi T, Sone H, Suzuki H, Yamada N: Diagnosis and management of type Ⅰ and type V hyperlipoproteinemia. J Atheroscler Thromb, 2012; 19: 1-12.
  • Arai H, Ishibashi S, Bujo H, Hayashi T, Yokoyama S, Oikawa S, Kobayashi J, Shirai K, Ota T, Yamashita S, Gotoda T, Harada-Shiba M, Sone H, Eto M, Suzuki H, Yamada N: Management of type IIb dyslipidemia. J Atheroscler Thromb, 2012; 19: 105-114.
  • Fujikura J, Nakao K, Sone M, Noguchi M, Mori E, Naito M, Taura D, Harada-Shiba M, Kishimoto I, Watanabe A, Asaka I, Hosoda K: Induced pluripotent stem cells generated from diabetic patients with mitochondrial DNA A3243G mutation. Diabetologia, 2012; 55: 1689-1698.
  • Uchida S, Itaka K, Chen Q, Osada K, Miyata K, Ishii T, Harada-Shiba M, Kataoka K: Combination of chondroitin sulfate and polyplex micelles from Poly(ethylene glycol)-poly{N'-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} block copolymer for prolonged in vivo gene transfection with reduced toxicity: J Control Release, 2011; 155(2): 296-302.
  • Harada K, Miyamoto Y, Morisaki H, Ohta N, Yamanaka I, Kokubo Y, Makino H, Harada-Shiba M, Okayama A, Tomoike H, Okamura T, Saito Y, Yoshimasa Y, Morisaki T: A novel Thr56Met mutation of the autosomal recessive hypercholesterolemia gene associated with hypercholesterolemia. J Atheroscler Thromb, 2010; 17(2): 131-140.
  • Kang J, Tachibana Y, Kanata W, Mahara A, Harada-Shiba M, Yamaoka T : Liver-targeted siRNA delivery by polyethyleneimine(PEI)-pullulan carrir. Bioorg Med Chem, 2010; 18: 3946-3950.
  • Fujita Y, Kakino A, Harada-Shiba M, Sato Y, Otsui K, Yoshimoto R, Sawamura T: C-Reactive protein uptake by macrophage cell line via Class-A scavenger receptor. Clin Chem, 2010; 56(3): 478-481.
  • Harada-Shiba M, Sugisawa T, Makino H, Abe M, Tsushima M, Yoshimasa Y, Yamashita T, Miyamoto Y, Yamamoto A, Tomoike H and Yokoyama S: Impact of statin treatment on the clinical fate of heterozygous familial hypercholesterolemia. J Atheroscler Thromb, 2010; 17:667-674.
  • Harada-Shiba M, Takamisawa I, Miyata K, Ishii T, Nishiyama N, Itaka K, Kangawa K, Yoshihara F, Asada Y, Hatakeyama K, Nagaya N and Kataoka K: Intratracheal gene transfer of adrenomedullin using polyplex nanomicelles attenuates monocrotaline-induced pulmonary hypertension in rats. Mol Ther, 2009; 17:1180-1186.
  • Watanabe K, Harada-Shiba M, Suzuki A, Gokuden R, Kurihara R, Sugao Y, Mori T, Katayama Y, Niidome T: In vivo siRNA delivery with dendritic poly(L-lysine) for the treatment of hypercholesterolemia. Mol Biosystems, 2009; 5: 1306-1310.
  • Shimano H, Arai H, Harada-Shiba M, Ueshima H, Ohta T, Yamashita S, Gotoda T, Kiyohara Y, Hayashi T, Kobayashi J, Shimamoto K, Bujo H, Ishibashi S, Shirai K, Oikawa S, Saito Y, Yamada N: Proposed guidelines for hypertriglyceridemia in japan with non-HDL cholesterol as the second target. J Atheroscler Thromb, 2008; 15(3): 116-121.
  • Yamashita S, Bujyo H, Ari H, Harada-Shiba M, Matsui S, Fukushima M, Saito Y, Kita T, Matsuzawa Y: Long-term probucol treatment prevents secondary cardiovascular events : a cohort study of patients with heterozygous familial hypercholesterolemia in Japan. J Atheroscler Throm, 2008; 15, 6: 292-303.
  • Makino H, Harada-Shiba M: Safety Aspects of Statins: Which Factors Create the Adverse Effects of Statins: Immum. Endoc.&Metab.Agents in Med.Chem, 2008; 8(2): 172-176.
  • Ichi I , Takashima Y , Adachi N , Nakahara K , Kamikawa C , Harada - Shiba M , Kojo S : Effects of Dietary Cholesterol on Tissue Ceramides and Oxidation products of Apolipoprotein B-100 in ApoE-Deficient Mice. Lipids, 2007; 42(10): 893-900.
  • Jo J, Nagaya N, Miyahata Y, Kataoka M, Harada-shiba M, Kangawa K, Tabata Y: Transplantation of genetically engineered mesenchymal stem cells improves cardiac function in rats with myocardial infarction: benefit of a novel nonviral vector, cationized dextran. Tissue Eng, 2007; 13(2): 31.
  • Ichi I, Nakahara K, Miyashita Y, Hidaka A, Kutsukake S, Inoue K, Maruyama T, Miwa Y, Harada-Shiba M, Tsushima M, Kojo S: Kisei Cohort Study Group: Association of ceramides in human plasma with risk factors of atherosclerosis. Lipids, 2006; 41(9): 859-863.
  • Yamamoto A, Harada-Shiba M, Endo M, Kusakabe N, Tanioka T, Kato H, Shoji T: The effect of ezetimibe on serum lipids and lipoproteins in patients with homozygous familial hypercholesterolemia undergoing LDL-apheresis therapy. Atherosclerosis, 2006; 186(1): 126-131.
  • Umeda M, Harada-Shiba M, Uchida K, Nakayama Y: Photo-control of the polyplexen formation between DNA and photo-cation generatable water-soluble polymers. Curr Drug Deliv. 2005; 2: 207-214.
  • Nakayama Y, Masuda T, Nagaishi M, Hayashi M, Ohira M, Harada-Shiba M: High performance gene delivery polymeric vector: Nano-Structured cationic star polymers(star vectors). Curr Drug Deliv, 2005; 2: 53-57.
  • Harada-Shiba M, Takagi A, Marutsuka K, Moriguchi S, Yagyu H, Ishibashi S, Asada Y and Yokoyama S: Disruption of autosomal recessive hypercholesterolemia gene shows different phenotype in vitro and in vivo. Circ Res, 2004; 95:945-952.
  • Makino H and Harada-Shiba M: Long-term effect of low-density lipoprotein apheresis in patients with homozygous familial hypercholesterolemia. Ther Apher Dial, 2003; 7:397-401.
  • Harada-Shiba M, Takagi A, Miyamoto Y, Tsushima M, Ikeda Y, Yokoyama S and Yamamoto A: Clinical features and genetic analysis of autosomal recessive hypercholesterolemia. J Clin Endocrinol Metab, 2003; 88:2541-2547.
  • Harada-Shiba M, Kinoshita M, Kamido H and Shimokado K: Oxidized low density lipoprotein induces apoptosis in cultured human umbilical vein endothelial cells by common and unique mechanisms. J Biol Chem, 1998; 273:9681-9687.
  • Nishimura N, Harada-Shiba M, Tajima S, Sugano R, Yamamura T, Qiang QZ and Yamamoto A: Acquisition of secretion of transforming growth factor-beta 1 leads to autonomous suppression of scavenger receptor activity in a monocyte-macrophage cell line, THP-1. J Biol Chem, 1998; 273:1562-1567.
  • Harada-Shiba M, Tajima S and Yamamoto A: Response of 3-hydroxy-3-methylglutaryl CoA reductase to l-triiodothyronine in cultured fibroblasts from FH homozygotes. Atherosclerosis, 1995; 113:91-98.
  • Harada-Shiba M, Tajima S, Yokoyama S, Miyake Y, Kojima S, Tsushima M, Kawakami M and Yamamoto A: Siblings with normal LDL receptor activity and severe hypercholesterolemia. Arterioscler Thromb, 1992; 12:1071-1078.
Academic Award Received  
Academic Degree 1984 M.D., (Shiga University of Medical Science)
1988 Ph.D., (Shiga University of Medical Science)
Academic Society Affiliation Japanese Atherosclerosis Society, The Japanese Society of Gene Design and Delivery, Japanese Society for Apheresis, Japan Diabetes Society, The Japanese Circulation Society, Japan Society of Gene Therapy, The Japanese Biochemical Society, The Molecular Biology Society of Japan, The Japanese Society of Internal Medicine
Educational Activity
  • Invited Professor of Osaka University
  • Adjunctive Professor of Kobe Gakuin University,
  • Lecturer of Shiga University of Medical Science,
  • Lecturer of University of Miyazaki
Other Activities Member of Science Council of Japan
Subcommittee member for lipid metabolism of Japan Atherosclerosis Society
Associate Editor of the Journal of Atherosclerosis and Thrombosis
Vice President of the Japanese Society of Gene Design and Delivery
Researcher Information http://jglobal.jst.go.jp/public/20090422/200901069729452309
http://rns.nii.ac.jp/nr/1000070271575
Link  

last updated：2022/06/27

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