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
 

Naomasa Makita, Professor, Chair

Research Interests

Familial sudden death syndrome is a disease entity describing different causes of sudden death in the young and middle-aged individuals. Development of strategies for pre-symptomatic diagnosis and prevention of individuals at-risk is an urgent issue in public health. Considerable efforts to identify the predisposing genes to lethal arrhythmias have made it feasible to establish effective diagnostic and preventive strategies especially in congenital long QT syndrome. However, pathophysiological mechanisms and preventive measures remain to be elucidated in other inherited arrhythmias such as Brugada syndrome, idiopathic ventricular fibrillation, or progressive cardiac conduction defect. We will focus on determining rare genetic substrates and the pathophysiological mechanisms underlying these life-threatening arrhythmias using electrophysiological, genetic and molecular biological techniques. Furthermore, we will make an effort to identify common variants that cause a subtle increase in the risk of life-threatening arrhythmias. These efforts will facilitate prevention of sudden cardiac death throughdevelopingexpedited technology to screen individuals with potential arrhythmogenic substrates, thereby leading to new treatment strategies.

Degrees

  • MD (Hokkaido University School of  Medicine  ’83)
  • PhD in Medical Science (Hokkaido University Graduate School of Medicine ’87)

Selected Publications

  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)

(Publication-list)

 

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