Nagasaki U Link
Nagasaki University Graduate School of Biomedical Sciences 長崎大学学院医歯薬学総合研究科
 

蒔田直昌 教授

教室の方針

家族性突然死症候群は若年・壮年者の突然死を惹起する予後不良の疾患であり、治療法開発が喫緊の課題である。家族性突然死症候群のうち研究が最も進んでいるのは先天性QT延長症候群で、保因者の発症前診断や遺伝子情報に基づく不整脈予防にも道が開けた。しかし、本邦に多いブルガダ症候群、特発性心室細動、進行性心臓伝導障害などの致死性不整脈では依然としてその病態メカニズムが十分に解明されていない。当教室の研究の目標は、電気生理学・遺伝学・分子生物学などを用いて、基礎医学の立場から家族性突然死症候群の原因と発症メカニズムを解明し、その研究成果を臨床にフィードバックすることである。

学位

  • 医師(1983年3月北海道大学医学部医学科卒業)

  • 医学博士(1987年3月北海道大学医学研究科博士課程修了)


業績

  1. 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 A, Thollet A, Fouchard S, Bonnaud S, Parent P, Shibata Y, Perrin J.P, Le Marec H, Hagiwara N, Mercier S, Horie M, Probst V, Yoshiura K.I, Redon R, Schott J.J, Makita N. Progressive atrial conduction system defects associated with bone malformation caused by a connexin45 mutation. J Am Coll Cardiol 70(3), 358-70 (2017).
  2. 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. Hum Mol Genet 29(9), 1670-1677 (2017).  (pdf)
  3. 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, Fukushima-Kusano K, Kamakura S, Yasuda S, Ogawa H, Y. M, Kapplinger J, Ackerman M, Shimizu W. Genotype-phenotype correlation of SCN5A mutation for clinical and electrocardiographic characteristics of probands with Brugada syndrome: A Japanese multicenter registry. Circulation 135(23), 2255-2270 (2017).  (pdf)
  4. 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 KI, 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(5), 717-724 (2017). (pdf)
  5. Daumy X, Amarouch MY, Lindenbaum P, Bonnaud S,Bianchi B, Nafzger S, Baron E, Fouchard S, Thollet A, Kyndt F, Barc J, Le Scouarnec S, Makita N, Le Marec H, Dina C, Gourraud J, Probst V, Abriel H, Redon R, Schott J. Targeted resequencing identifies TRPM4 as a major gene predisposing to progressive familial heart block type I.Int J Cardiol. 2016; 207:349-358 (pdf)
  6. Nademanee K, Raju H, de Noronha S, Papadakis M, Robinson L, Rothery S, Makita N, Kowase S, Boonmee N, Vitayakritsirikul V, Ratanarapee S, Sharma S, van der Wal A, Christiansen M, Tan Hanno, Wilde A, Nogami A, Sheppard M, Gumpanart V, Behr E.”Fibrosis, Connexin43 and Conduction Abnormalities in the Brugada Syndrome”. J Am Coll Cardiol. 2015; 66(18):1976-1986. (pdf) (PubMed: 26516000)
  7. Hayashi K, Konno T, Tada H, Tani S, Liu L, Fujino N, Nohara A, Hodatsu A, Tsuda T, Tanaka Y, Kawashiri M, Ino H, Makita N, Yamagishi M. Functional Characterization of Rare Variants Implicated in Susceptibility to Lone Atrial Fibrillation.  Circ Arrhythm Electrophysiol.2015; 8: 1095-1104 (pdf) (Supplement)(PubMed: 26129877)
  8. Harrell DT, Ashihara T, Ishikawa T, Tominaga I, Mazzanti A, Takahashi K, Oginosawa Y, Abe H, Maemura K, Sumitomo N, Uno K, Takano M, Priori, Makita N. Genotype-dependent difference in age of manifestation and arrhythmia complication in short QT syndrome. Int J Cardiol. 2015;190:393-402. (pdf) (Supplement) (PubMed: 25974115)
  9. Ishikawa T, Jou CJ, Nogami A, Kowase S, Arrington CB, Spencer M. Barnett SM, Harrell DT, Arimura T, Tsuji Y, Kimura A, Makita N. A novel mutation in the α-myosin heavy chain gene is associated with sick sinus syndrome. Circ Arrhythm Electrophysiol.2015; 8: 400-408. (pdf) (PubMed: 25717017)
  10. Makita N, Yagihara N, Crotti L, Johnson CN, Beckmann BM, Roh MS, Shigemizu D, Lichtner P, Ishikawa T, Aiba T, Homfray T, Behr ER, Klug D, Denjoy I, Mastantuono E, Theisen D, Tsunoda T, Satake W, Toda T, Nakagawa H, Tsuji Y, Tsuchiya T, Yamamoto H, Miyamoto Y, Endo N, Kimura A, Ozaki K, Motomura H, Suda K, Tanaka T, Schwartz PJ, Meitinger T, Kaab S, Guicheney P, Shimizu W, Bhuiyan ZA, Watanabe H, Chazin WJ and George AL. Novel Calmodulin (CALM2) Mutations Associated with Congenital Arrhythmia SusceptibilityCirc Cardiovasc Genet 2014;7:466-474. (pdf) (PubMed: 24917665)
  11. Abe K, Machida T, Sumitomo N, Yamamoto H, Ohkubo K, Watanabe I, Makiyama T, Fukae S, Kohno M, Harrell DT, Ishikawa T, Tsuji Y, Nogami A, Watabe T, Oginosawa Y, Abe H, Maemura K, Motomura H, Makita N. Sodium Channelopathy Underlying Familial Sick Sinus Syndrome with Early Onset and Predominantly Male CharacteristicsCirc Arrhythm Electrophysiol.2014;7:511-517(pdf) (PubMed: 24762805)
  12. Bezzina CR, Barc J, Mizusawa Y, Remme CA, Gourraud J-B, Simonet F, Verkerk AO, Schwartz PJ, Crotti L, Dagradi F, Guicheney P, Fressart V, Leenhardt A, Antzelevitch C, Bartkowiak S, Schulze-Bahr E, Zumhagen S, Behr ER, Bastiaenen R, Tfelt-Hansen J, Olesen MS, Kaab S, Beckmann BM, Weeke P, Watanabe H, Endo N, Minamino T, Horie M, Ohno S, Hasegawa K, Makita N, Nogami A, Shimizu W, Aiba T, Froguel P, Balkau B, Lantieri O, Torchio M, Wiese C, Weber D, Wolswinkel R, Coronel R, Boukens BJ, Bezieau S, Charpentier E, Chatel S, Despres A, Gros F, Kyndt F, Lecointe S, Lindenbaum P, Portero V, Violleau J, Gessler M, Tan HL, Roden DM, Christoffels VM, Marec HL, Wilde AA, Probst V, Schott JJ, Dina C, Redon R. Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death.  Nat. Genet. 45, 1044-1049, 2013  (pdf)  (PubMed: 23872634)
  13. Ishikawa T, Sato A, Marcou CA, Tester DJ, Ackerman MJ, Crotti L, Schwartz PJ, On YK, Park JE, Nakamura K, Hiraoka M, Nakazawa K, Sakurada H, Arimura T, Makita N, Kimura A. A novel disease gene for Brugada syndrome: sarcolemmal membrane-associated protein gene mutations impair intracellular trafficking of hNav1.5Circ Arrhythm Electrophysiol. 5:1098-1107,2012 (pdf) (PubMed: 23064965)
  14. Makita N, Seki A, Sumitomo N, Chkourko H, Fukuhara S, Watanabe H, Shimizu W, Bezzina CR, Hasdemir C, Mugishima H, Makiyama T, Baruteau A, Baron E, Horie M, Hagiwara N, Wilde AA, Probst V, Le Marec H, Roden DM, Mochizuki N, Schott JJ, Delmar M. A connexin40 mutation associated with a malignant variant of progressive familial heart block type ICirc Arrhythm Electrophysiol, 5:163-172, 2012 (pdf) (PubMed: 22247482)
  15. Makita N, Behr E, Shimizu W, Horie M, Sunami A, Crotti L, Schulze-Bahr E, Fukuhara S, Mochizuki N, Makiyama T, Itoh H, Christiansen M, McKeown P, Miyamoto K, Kamakura S, Tsutsui H, Schwartz PJ, George AL Jr, Roden DM (2008). The E1784K mutation in SCN5A is associated with mixed phenotype of type 3 long QT syndrome. J Clin Invest 118, 2219-2229, 2008. (pdf) (PubMed: 18451998)
  16. Makita N, Horie M, Nakamura T, Ai T, Sasaki K, Yokoi H, Sakurai M, Sakuma I, Otani H, Sawa H, Kitabatake A. Drug-induced long-QT syndrome associated with a subclinical SCN5A mutationCirculation 106, 1269-1274, 2002  (pdf) (PubMed: 12208804)
  17. Makita N, Shirai N, Wang DW, Sasaki K, George AL Jr. Kanno M, and Kitabatake A. Cardiac Na+ channel dysfunction in the Brugada syndrome is aggravated by b1 subunitCirculation 101, 54-60, 2000 (pdf)
  18. Bennett PB, Yazawa K, Makita N, George Al. Molecular mechanism for an inherited cardiac arrhythmiaNature 376, 683-685,1995 (pdf) (PubMed: 7651517)

(分子生理学研究室 業績集)  (Publication-list-6-22-2017 )

 

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