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分子生物学部

業績

2018年の業績

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Crisper-Cas9システムを用いたゲノム編集技術を導入することにより、センター内における疾患モデル動物作成の支援を行っています。

2018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. 肥大型心筋症患者の症状と病理像・遺伝型との関連を調べるため、全エクソン解析を実施した。
  3. カテコラミン誘発性多型性心室頻拍 (CPVT) 患者の登録を行い、遺伝学的背景を明らかにするとともに、新規治療薬候補のスクリーニングを実施した。

研究業績

  1. Zankov DP, Salloum FN, Jiang M and Tseng GN. Chronic in vivo angiotensin II administration differentially modulates the slow delayed rectifier channels in atrial and ventricular myocytes. Heart Rhythm. 2019;16:108-116.
  2. Yokokawa T, Ichimura S, Hijioka N, Kaneshiro T, Yoshihisa A, Kunii H, Nakazato K, Ishida T, Suzuki O, Ohno S, Aiba T, Ohtani H and Takeishi Y. Case reports of a c.475G>T, p.E159* lamin A/C mutation with a family history of conduction disorder, dilated cardiomyopathy and sudden cardiac death. BMC cardiovascular disorders. 2019;19:298.
  3. Yamada N, Asano Y, Fujita M, Yamazaki S, Inanobe A, Matsuura N, Kobayashi H, Ohno S, Ebana Y, Tsukamoto O, Ishino S, Takuwa A, Kioka H, Yamashita T, Hashimoto N, Zankov DP, Shimizu A, Asakura M, Asanuma H, Kato H, Nishida Y, Miyashita Y, Shinomiya H, Naiki N, Hayashi K, Makiyama T, Ogita H, Miura K, Ueshima H, Komuro I, Yamagishi M, Horie M, Kawakami K, Furukawa T, Koizumi A, Kurachi Y, Sakata Y, Minamino T, Kitakaze M and Takashima S. Mutant KCNJ3 and KCNJ5 Potassium Channels as Novel Molecular Targets in Bradyarrhythmias and Atrial Fibrillation. Circulation. 2019;139:2157-5169.
  4. Wu Q, Hayashi H, Hira D, Sonoda K, Ueshima S, Ohno S, Makiyama T, Terada T, Katsura T, Miura K and Horie M. Genetic variants of alcohol-metabolizing enzymes in Brugada syndrome: Insights into syncope after drinking alcohol. J Arrhythm. 2019;35:752-759.
  5. Wakisaka KT, Tanaka R, Hirashima T, Muraoka Y, Azuma Y, Yoshida H, Tokuda T, Asada S, Suda K, Ichiyanagi K, Ohno S, Itoh M and Yamaguchi M. Novel roles of Drosophila FUS and Aub responsible for piRNA biogenesis in neuronal disorders. Brain research. 2019;1708:207-219.
  6. van der Werf C, Lieve KV, Bos JM, Lane CM, Denjoy I, Roses-Noguer F, Aiba T, Wada Y, Ingles J, Leren IS, Rudic B, Schwartz PJ, Maltret A, Sacher F, Skinner JR, Krahn AD, Roston TM, Tfelt-Hansen J, Swan H, Robyns T, Ohno S, Roberts JD, van den Berg MP, Kammeraad JA, Probst V, Kannankeril PJ, Blom NA, Behr ER, Borggrefe M, Haugaa KH, Semsarian C, Horie M, Shimizu W, Till JA, Leenhardt A, Ackerman MJ and Wilde AA. Implantable cardioverter-defibrillators in previously undiagnosed patients with catecholaminergic polymorphic ventricular tachycardia resuscitated from sudden cardiac arrest. Eur Heart J. 2019;40:2953-2961.
  7. Takayama K, Ohno S, Ding WG, Ashihara T, Fukumoto D, Wada Y, Makiyama T, Kise H, Hoshiai M, Matsuura H and Horie M. A de novo gain-of-function KCND3 mutation in early repolarization syndrome. Heart Rhythm. 2019;16:1698-1706.
  8. Takaki T, Inagaki A, Chonabayashi K, Inoue K, Miki K, Ohno S, Makiyama T, Horie M and Yoshida Y. Optical Recording of Action Potentials in Human Induced Pluripotent Stem Cell-Derived Cardiac Single Cells and Monolayers Generated from Long QT Syndrome Type 1 Patients. Stem cells international. 2019;2019:7532657.
  9. Shimizu W, Makimoto H, Yamagata K, Kamakura T, Wada M, Miyamoto K, Inoue-Yamada Y, Okamura H, Ishibashi K, Noda T, Nagase S, Miyazaki A, Sakaguchi H, Shiraishi I, Makiyama T, Ohno S, Itoh H, Watanabe H, Hayashi K, Yamagishi M, Morita H, Yoshinaga M, Aizawa Y, Kusano K, Miyamoto Y, Kamakura S, Yasuda S, Ogawa H, Tanaka T, Sumitomo N, Hagiwara N, Fukuda K, Ogawa S, Aizawa Y, Makita N, Ohe T, Horie M and Aiba T. Association of Genetic and Clinical Aspects of Congenital Long QT Syndrome With Life-Threatening Arrhythmias in Japanese Patients. JAMA cardiology. 2019;4:246-254.
  10. Sakamoto N, Natori S, Hosoguchi S, Minoshima A, Noro T, Akasaka K, Sato N, Ohno S, Ikeda Y, Ishibashi-Ueda H, Horie M and Hasebe N. Left-Dominant Arrhythmogenic Cardiomyopathy With Heterozygous Mutations in DSP and MYBPC3. Circulation Cardiovascular imaging. 2019;12:e008913.
  11. Kawai H, Watanabe E, Ohno S, Horie M and Ozaki Y. Cardiac Arrest Associated with Both an Anomalous Left Coronary Artery and KCNE1 Polymorphism. International heart journal. 2019;60:1003-1005.
  12. Horigome H, Ishikawa Y, Kokubun N, Yoshinaga M, Sumitomo N, Lin L, Kato Y, Tanabe-Kameda Y, Ohno S, Nagashima M and Horie M. Multivariate analysis of TU wave complex on electrocardiogram in Andersen-Tawil syndrome with KCNJ2 mutations. Ann Noninvasive Electrocardiol. 2019:e12721.
  13. Honda M, Tsuchimochi H, Hitachi K and Ohno S. Transcriptional cofactor Vgll2 is required for functional adaptations of skeletal muscle induced by chronic overload. Journal of cellular physiology. 2019.(In Press)
  14. Hasegawa K, Morishita T, Miyanaga D, Hisazaki K, Kaseno K, Miyazaki S, Uzui H, Ohno S, Horie M and Tada H. Medical Castration is a Rare but Possible Trigger of Torsade de Pointes and Ventricular Fibrillation. International heart journal. 2019;60:193-198.
  15. Fujihara Y, Noda T, Kobayashi K, Oji A, Kobayashi S, Matsumura T, et al. Identification of multiple male reproductive tract-specific proteins that regulate sperm migration through the oviduct in mice. Proc Natl Acad Sci U S A 2019;116:18498-18506.
  16. Fujita S, Nakagawa R, Futatani T, Igarashi N, Fuchigami T, Saito S, Ohno S, Horie M and Hatasaki K. Long QT syndrome with a de novo CALM2 mutation in a 4-year-old boy. Pediatr Int. 2019;61:852-858.
  17. Dharmawan T, Nakajima T, Ohno S, Iizuka T, Tamura S, Kaneko Y, Horie M and Kurabayashi M. Identification of a novel exon3 deletion of RYR2 in a family with catecholaminergic polymorphic ventricular tachycardia. Ann Noninvasive Electrocardiol. 2019:e12623.
  18. Crotti L, Spazzolini C, Tester DJ, Ghidoni A, Baruteau AE, Beckmann BM, Behr ER, Bennett JS, Bezzina CR, Bhuiyan ZA, Celiker A, Cerrone M, Dagradi F, De Ferrari GM, Etheridge SP, Fatah M, Garcia-Pavia P, Al-Ghamdi S, Hamilton RM, Al-Hassnan ZN, Horie M, Jimenez-Jaimez J, Kanter RJ, Kaski JP, Kotta MC, Lahrouchi N, Makita N, Norrish G, Odland HH, Ohno S, Papagiannis J, Parati G, Sekarski N, Tveten K, Vatta M, Webster G, Wilde AAM, Wojciak J, George AL, Ackerman MJ and Schwartz PJ. Calmodulin mutations and life-threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry. Eur Heart J. 2019;40:2964-2975.
  19. Yoshinaga M, Kucho Y, Ushinohama H, Ishikawa Y, Ohno S and Ogata H. Autonomic Function and QT Interval During Night-Time Sleep in Infant Long QT Syndrome. Circ J. 2018;82:2152-2159.
  20. Yagi N, Itoh H, Hisamatsu T, Tomita Y, Kimura H, Fujii Y, Makiyama T, Horie M and Ohno S. A challenge for mutation specific risk stratification in long QT syndrome type 1. J Cardiol. 2018;72:56-65.
  21. Wuriyanghai Y, Makiyama T, Sasaki K, Kamakura T, Yamamoto Y, Hayano M, Harita T, Nishiuchi S, Chen J, Kohjitani H, Hirose S, Yokoi F, Gao J, Chonabayashi K, Watanabe K, Ohno S, Yoshida Y, Kimura T and Horie M. Complex aberrant splicing in the induced pluripotent stem cell-derived cardiomyocytes from a patient with long-QT syndrome carrying KCNQ1-A344Aspl mutation. Heart Rhythm. 2018;15:1566-1574.
  22. Wu J, Mizusawa Y, Ohno S, Ding WG, Higaki T, Wang Q, Kohjitani H, Makiyama T, Itoh H, Toyoda F, James AF, Hancox JC, Matsuura H and Horie M. A hERG mutation E1039X produced a synergistic lesion on IKs together with KCNQ1-R174C mutation in a LQTS family with three compound mutations. Scientific reports. 2018;8:3129.
  23. Wakisaka KT, Ichiyanagi K, Ohno S and Itoh M. Association of zygotic piRNAs derived from paternal P elements with hybrid dysgenesis in Drosophila melanogaster. Mobile DNA. 2018;9:7.
  24. Ueshima S, Hira D, Kimura Y, Fujii R, Tomitsuka C, Yamane T, Tabuchi Y, Ozawa T, Itoh H, Ohno S, Horie M, Terada T and Katsura T. Population pharmacokinetics and pharmacogenomics of apixaban in Japanese adult patients with atrial fibrillation. British journal of clinical pharmacology. 2018;84:1301-1312.
  25. Sonoda K, Ohno S, Ozawa J, Hayano M, Hattori T, Kobori A, Yahata M, Aburadani I, Watanabe S, Matsumoto Y, Makiyama T and Horie M. Copy number variations of SCN5A in Brugada syndrome. Heart Rhythm. 2018;15:1179-1188.
  26. Seki S, Yamashita E, Tanoue K, Nuruki N, Sonoda M, Ohno S, Ishibashi-Ueda H, Tanaka Y and Yoshinaga M. Prediagnostic electrocardiographic and echocardiographic findings of biopsy-proven hypertrophic cardiomyopathy. Journal of Arrhythmia. 2018;34:643-646.
  27. Saito A, Ohno S, Nuruki N, Nomura Y, Horie M and Yoshinaga M. Three cases of catecholaminergic polymorphic ventricular tachycardia with prolonged QT intervals including two cases of compound mutations. J Arrhythm. 2018;34:291-293.
  28. Ozawa J, Ohno S, Saito H, Saitoh A, Matsuura H and Horie M. A novel CACNA1C mutation identified in a patient with Timothy syndrome without syndactyly exerts both marked loss-and-gain of function effects. HeartRhythm Case Reports. 2018;4:273-277.
  29. Ozawa J, Ohno S, Fujii Y, Makiyama T, Suzuki H, Saitoh A and Horie M. Differential Diagnosis Between Catecholaminergic Polymorphic Ventricular Tachycardia and Long QT Syndrome Type 1- Modified Schwartz Score. Circ J. 2018;82:2269-2276.
  30. Nakajima K, Aiba T, Makiyama T, Nishiuchi S, Ohno S, Kato K, Yamamoto Y, Doi T, Shizuta S, Onoue K, Yagihara N, Ishikawa T, Watanabe I, Kawakami H, Oginosawa Y, Murakoshi N, Nogami A, Aonuma K, Saito Y, Kimura T, Yasuda S, Makita N, Shimizu W, Horie M and Kusano K. Clinical Manifestations and Long-Term Mortality in Lamin A/C Mutation Carriers From a Japanese Multicenter Registry. Circ J. 2018;28:2707-2714.
  31. Nakagawa Y, Nishikimi T, Sakai H, Ohno S, Kinoshita H, Inazumi H, Moriuchi K, Kuwahara K, Horie M and Kimura T. Macro-pro-B-type natriuretic peptide (proBNP) and hidden macro-N-terminal proBNP: Case report. Clinical biochemistry. 2018;52:148-152.
  32. Murayama T, Ogawa H, Kurebayashi N, Ohno S, Horie M and Sakurai T. A tryptophan residue in the caffeine-binding site of the ryanodine receptor regulates Ca2+ sensitivity. Communications Biology. 2018;1:98.
  33. Miyata K, Ohno S, Itoh H and Horie M. Bradycardia is a Specific Phenotype of Catecholaminergic Polymorphic Ventricular Tachycardia Induced by RYR2 Mutations. Internal medicine (Tokyo, Japan). 2018;57:1813-1817.
  34. Kise H, Ohno S, Kono Y, Yoshizawa M, Harama D, Okafuji A, Toda T, Koizumi K, Hoshiai M, Sugita K and Horie M. Electrical storm in an infant with short‐coupled variant of torsade de pointes. Journal of Arrhythmia. 2018;34:315-318.
  35. Hisamatsu T, Miura K, Ohkubo T, Arima H, Fujiyoshi A, Satoh A, Kadota A, Zaid M, Takashima N, Ohno S, Horie M and Ueshima H. Home blood pressure variability and subclinical atherosclerosis in multiple vascular beds: a population-based study. Journal of hypertension. 2018;36:2193-2203.
  36. Harada M, Suzuki H, Ohno S, Ozawa J, Saitoh A and Horie M. Dynamic QT Changes in Long QT Syndrome Type 8. Circ J. 2018;83:1614.
  37. Fukumoto D, Ding WG, Wada Y, Fujii Y, Ichikawa M, Takayama K, Fukuyama M, Kato K, Itoh H, Makiyama T, Omatsu-Kanbe M, Matsuura H, Horie M and Ohno S. Novel intracellular transport-refractory mutations in KCNH2 identified in patients with symptomatic long QT syndrome. J Cardiol. 2018;71:401-408.
  38. Fujihara Y, Oji A, Kojima-Kita K, Larasati T and Ikawa M. Co-expression of sperm membrane proteins CMTM2A and CMTM2B is essential for ADAM3 localization and male fertility in mice. Journal of Cell Science. 2018;131:jcs221481.
  39. Fujita S, Nishida K, Irabu H, Nakagawa R, Futatani T, Igarashi N, Usuda K, Nagata Y, Ohno S, Horie M and Hatasaki K. Catecholaminergic polymorphic ventricular tachycardia managed as orthostatic dysregulation and epilepsy in 11- and 15-year-old sisters. Pediatr Int. 2018;60:998-1001.
  40. Aizawa Y, Fujisawa T, Katsumata Y, Kohsaka S, Kunitomi A, Ohno S, Sonoda K, Hayashi H, Hojo R, Fukamizu S, Nagase S, Ito S, Nakajima K, Nishiyama T, Kimura T, Kurita Y, Furukawa Y, Takatsuki S, Ogawa S, Nakazato Y, Sumiyoshi M, Kosaki K, Horie M and Fukuda K. Sex-Dependent Phenotypic Variability of an SCN5A Mutation: Brugada Syndrome and Sick Sinus Syndrome. Journal of the American Heart Association. 2018;7:e009387.

過去の業績

最終更新日:2021年10月22日

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