分子生物学部
研究活動の概要

　ヒトは30億塩基対からなるゲノムによって、その遺伝的背景が決まっています。そして、そのゲノムのほんの一部の変化によって、多くの遺伝性疾患は発症します。分子生物学部では、単一遺伝子の変異によって発症すると考えられている遺伝性不整脈や心筋症などの遺伝性循環器疾患について、次世代シークエンサー等の機器を用いて、その遺伝的な原因を明らかにします。そして遺伝的背景生じる疾患発症へのメカニズムを電気生理学的、生化学的手法を用いて明らかにし、そこで得られた知見を元に、有効な治療薬の開発に結びつけていきます。
　また単一遺伝子によって発症する疾患のみならず、ゲノムワイド関連解析などの手法を用い、弱い作用を持つ遺伝子多型の違いによって、どのように循環器疾患発症リスクが異なっているのか、解析を進めていきます。
　さらに生活習慣病の予防にも直結する、骨格筋の線維型の決定及び維持機構について、モデル動物を用いて解析しています。

2017年の主な研究成果
  1. J波症候群の患者に、一過性外向きカリウム電流チャネルをコードするKCND3の新規突然変異を同定した。電気生理学的な機能解析で、機能獲得型変異であることを明らかにし、キニジンの有効性を証明した。
  2. 骨格筋の線維型維持機構の解明に向けて、Vgll2が運動時の骨格筋の遅筋化に関与するかどうかを明らかにするために、代償性運動負荷試験を実施し、詳細な解析を行った。
研究業績
  1. Aoki R, Srivatanakul K, Osada T, Hotta K, Sorimachi T, Matsumae M, Morisaki H. Endovascular treatment of a dural arteriovenous fistula in a patient with Loeys-Dietz syndrome: A case report. Interventional Neuroradiology. 23, 206-210, 2017.
  2. Bae CR, Hino J, Hosoda H, Arai Y, Son C, Makino H, Tokudome T, Tomita T, Kimura T, Nojiri T, Hosoda K, Miyazato M, Kangawa K. Overexpression of C-type Natriuretic Peptide in Endothelial Cells Protects against Insulin Resistance and Inflammation during Diet-induced Obesity. Scientific Reports. 7, 9807, 2017.
  3. Fujiyoshi T, Minatoya K, Ikeda Y, Ishibashi-Ueda H, Morisaki T, Morisaki H, Ogino H. Impact of connective tissue disease on the surgical outcomes of aortic dissection in patients with cystic medial necrosis. Journal of Cardiothoracic Surgery. 12, 97, 2017.
  4. Hino J, Nakatani M, Arai Y, Tsuchida K, Shirai M, Miyazato M, Kangawa K. Overexpression of bone morphogenetic protein-3b (BMP-3b) in adipose tissues protects against high-fat diet-induced obesity. International Journal of Obesity. 41, 483-488, 2017.
  5. Hirashiki A, Adachi S, Nakano Y, Kamimura Y, Ogo T, Nakanishi N, Morisaki T, Morisaki H, Shimizu A, Toba K, Murohara T, Kondo T. Left main coronary artery compression by a dilated main pulmonary artery and left coronary sinus of Valsalva aneurysm in a patient with heritable pulmonary arterial hypertension and FLNA mutation. Pulmonary Circulation. 7, 734-740, 2017.
  6. Honda M, Hidaka K, Fukada S, Sugawa R, Shirai M, Ikawa M, Morisaki T. Vestigial-like 2 contributes to normal muscle fiber type distribution in mice. Scientific Reports. 7, 7168, 2017.
  7. Hudoyo AW, Hirase T, Tandelillin A, Honda M, Shirai M, Cheng J, Morisaki H, Morisaki T. Role of AMPD2 in impaired glucose tolerance induced by high fructose diet. Molecular Genetics and Metabolism Reports. 13, 23-29, 2017.
  8. Seike Y, Minatoya K, Sasaki H, Tanaka H, Itonaga T, Inoue Y, Morisaki H, Morisaki T, Ishibashi-Ueda H, Kobayashi J. Clinical outcomes of aortic repair in young adult patients with ACTA2 mutations. General Thoracic and Cardiovascular Surgery. 65, 686-691, 2017.
  9. Tatebe S, Sugimura K, Aoki T, Yamamoto S, Yaoita N, Suzuki H, Sato H, Kozu K, Konno R, Satoh K, Fukuda K, Adachi O, Saito R, Nakanishi N, Morisaki H, Oyama K, Saiki Y, Okada Y, Shimokawa H. The Efficacy of a Genetic Analysis of the BMPR2 Gene in a Patient with Severe Pulmonary Arterial Hypertension and an Atrial Septal Defect Treated with Bilateral Lung Transplantation. Internal Medicine. 56, 3193-3197, 2017.
  10. Hayano M, Makiyama T, Kamakura T, Watanabe H, Sasaki K, Funakoshi S, Wuriyanghai Y, Nishiuchi S, Harita T, Yamamoto Y, Kohjitani H, Hirose S, Yokoi F, Chen J, Baba O, Horie T, Chonabayashi K, Ohno S, Toyoda F, Yoshida Y, Ono K, Horie M, Kimura T. Development of a Patient-Derived Induced Pluripotent Stem Cell Model for the Investigation of SCN5A-D1275N-Related Cardiac Sodium Channelopathy. Circulation Journal. 81, 1783-1791, 2017.
  11. Yamagata K, Horie M, Aiba T, Ogawa S, Aizawa Y, Ohe T, Yamagishi M, Makita N, Sakurada H, Tanaka T, Shimizu A, Hagiwara N, Kishi R, Nakano Y, Takagi M, Makiyama T, Ohno S, Fukuda K, Watanabe H, Morita H, Hayashi K, Kusano K, Kamakura S, Yasuda S, Ogawa H, Miyamoto Y, Kapplinger JD, Ackerman MJ, Shimizu W. Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome: A Japanese Multicenter Registry. Circulation. 135, 2255-2270, 2017.
  12. Ohno S, Horie M. Molecular Genetics of ERS. Early Repolarization Syndrome. 23-31, 2017.
  13. Ishibashi K, Aiba T, Kamiya C, Miyazaki A, Sakaguchi H, Wada M, Nakajima I, Miyamoto K, Okamura H, Noda T, Yamauchi T, Itoh H, Ohno S, Motomura H, Ogawa Y, Goto H, Minami T, Yagihara N, Watanabe H, Hasegawa K, Terasawa A, Mikami H, Ogino K, Nakano Y, Imashiro S, Fukushima Y, Tsuzuki Y, Asakura K, Yoshimatsu J, Shiraishi I, Kamakura S, Miyamoto Y, Yasuda S, Akasaka T, Horie M, Shimizu W, Kusano K. Arrhythmia risk and β-blocker therapy in pregnant women with long QT syndrome. Heart. 103, 1374-1379, 2017.
  14. Ishikawa T, Ohno S, Murakami T, Yoshida K, Mishima H, Fukuoka T, Kimoto H, Sakamoto R, Ohkusa T, Aiba T, Nogami A, Sumitomo N, Shimizu W, Yoshiura K, Horigome H, Horie M, Makita N. Sick sinus syndrome with HCN4 mutations shows early onset and frequent association with atrial fibrillation and left ventricular noncompaction. Heart Rhythm. 14, 717-724, 2017.
  15. Kimura Y, Noda T, Matsuyama T, Otsuka Y, Kamakura T, Wada M, Ishibashi K, Inoue Y, Miyamoto K, Okamura H, Nagase S, Aiba T, Kamakura S, Noguchi T, Anzai T, Satomi K, Wada Y, Ohno S, Horie M, Shimizu W, Yasuda S, Shimokawa H, Kusano K. Heart failure in patients with arrhythmogenic right ventricular cardiomyopathy: What are the risk factors? International Journal of Cardiology. 241, 288-294, 2017.
  16. Wada Y, Ohno S, Aiba T, Horie M. Unique genetic background and outcome of non-Caucasian Japanese probands with arrhythmogenic right ventricular dysplasia/cardiomyopathy. Molecular Genetics & Genomic Medicine. 5, 639-651, 2017.
  17. Nishiuchi S, Makiyama T, Aiba T, Nakajima K, Hirose S, Kohjitani H, Yamamoto Y, Harita T, Hayano M, Wuriyanghai Y, Chen J, Sasaki K, Yagihara N, Ishikawa T, Onoue K, Murakoshi N, Watanabe I, Ohkubo K, Watanabe H, Ohno S, Doi T, Shizuta S, Minamino T, Saito Y, Oginosawa Y, Nogami A, Aonuma K, Kusano K, Makita N, Shimizu W, Horie M, Kimura T. Gene-Based Risk Stratification for Cardiac Disorders in LMNA Mutation Carriers. Circulation: Cardiovascular Genetics. 10, e001603, 2017.
  18. Sonoda K, Ohno S, Otuki S, Kato K, Yagihara N, Watanabe H, Makiyama T, Minamino T, Horie M. Quantitative analysis of PKP2 and neighbouring genes in a patient with arrhythmogenic right ventricular cardiomyopathy caused by heterozygous PKP2 deletion. Europace. 19, 644-650, 2017.
  19. Fujii Y, Itoh H, Ohno S, Murayama T, Kurebayashi N, Aoki H, Blancard M, Nakagawa Y, Yamamoto S, Matsui Y, Ichikawa M, Sonoda K, Ozawa T, Ohkubo K, Watanabe I, Guicheney P, Horie M. A type 2 ryanodine receptor variant associated with reduced Ca2+ release and short-coupled torsades de pointes ventricular arrhythmia. Heart Rhythm. 14, 98-107, 2017.
  20. Yamamoto Y, Makiyama T, Harita T, Sasaki K, Wuriyanghai Y, Hayano M, Nishiuchi S, Kohjitani H, Hirose S, Chen J, Yokoi F, Ishikawa T, Ohno S, Chonabayashi K, Motomura H, Yoshida Y, Horie M, Makita N, Kimura T. Allele-specific ablation rescues electrophysiological abnormalities in a human iPS cell model of long-QT syndrome with a CALM2 mutation. Human Molecular Genetics. 26, 1670-1677, 2017.
  21. Seki A, Ishikawa T, Daumy X, Mishima H, Barc J, Sasaki R, Nishii K, Saito K, Urano M, Ohno S, Otsuki S, Kimoto H, Baruteau AE, Thollet A, Fouchard S, Bonnaud S, Parent P, Shibata Y, Perrin JP, Le Marec H, Hagiwara N, Mercier S, Horie M, Probst V, Yoshiura KI, Redon R, Schott JJ, Makita N. Progressive Atrial Conduction Defects Associated With Bone Malformation Caused by a Connexin-45 Mutation. Journal of the American College of Cardiology. 70, 358-370, 2017.
  22. Aoki H, Nakamura Y, Ohno S, Makiyama T, Horie M. Cardiac conduction defects and Brugada syndrome: A family with overlap syndrome carrying a nonsense SCN5A mutation. Journal of Arrhythmia. 33, 35-39, 2017.
  23. Fujii Y, Matsumoto Y, Hayashi K, Ding WG, Tomita Y, Fukumoto D, Wada Y, Ichikawa M, Sonoda K, Ozawa J, Makiyama T, Ohno S, Yamagishi M, Matsuura H, Horie M, Itoh H. Contribution of a KCNH2 variant in genotyped long QT syndrome: Romano-Ward syndrome under double mutations and acquired long QT syndrome under heterozygote. Journal of Cardiology. 70, 74-79, 2017.
  24. Kojima A, Shikata F, Okamura T, Higaki T, Ohno S, Horie M, Uchita S, Kawanishi Y, Namiguchi K, Yasugi T, Izutani H. Refractory ventricular fibrillations after surgical repair of atrial septal defects in a patient with CACNA1C gene mutation - case report. Journal of Cardiothoracic Surgery. 12, 118, 2017.
  25. Shirai Y, Goya M, Ohno S, Horie M, Doi S, Isobe M, Hirao K. Elimination of Ventricular Arrhythmia in Catecholaminergic Polymorphic Ventricular Tachycardia by Targeting "Catecholamine-Sensitive Area": A Dominant-Subordinate Relationship between Origin Sites of Bidirectional Ventricular Premature Contractions. Pacing and Clinical Electrophysiology: PACE. 40, 600-604, 2017.