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About NCVC About NCVC About NCVC TOP The Center's Mission Organization History of the NCVC Location News Releases Close Hospital Hospital Hospital TOP About the Hospital The Group of Treatment Close Research Institute Research Institute Research Institute TOP About the Research Institute Departments Office for the Promotion of Diversity and Inclusion Research Institute and Open Innovation Center Brochure Close Open Innovation Center Open Innovation Center Open Innovation Center TOP Research Institute and Open Innovation Center Brochure Close Pamphlet National Cerebral and CardiovascularCenter Hospital Res. Inst. OICOpen Innovation Center Access Background White Black Japanese Access Menu National Cerebral and Cardiovascular Center TOP Research Institute Departments Department of Molecular Pharmacology Research Institute Department of Molecular Pharmacology   Member Director Yasunori Shintani Laboratory Chief Satoru Yamazaki Yuya Nishida Kentaro Otani Staff Scientist Yusuke Takahashi Research fellow Tasneem Qaqorh Kohei Sameshima Research scientist Issei Yazawa Kohei Tonai Graduate Student Eman Elrefaei Haruka Egami Takumi Tateno Research assistant Satomi Kobayashi Akiko Ogai Sonoko Adachi Research The structure of proteins exerts their function, which is key to understanding evolution and life. Abnormalities in protein function or structure eventually cause human diseases. It is necessary to carry out biochemical experiments that are fine-tuned to the distinct properties of each protein to understand the function and structure of proteins. We use various methods, including structural biology, biochemistry, pharmacology, genetics, molecular biology, and computational chemistry, to identify rational therapeutic target molecules and investigate their functions and failures in diseases. Our ultimate goal is to create new treatments by fully using them. Recent research topic is that we identify a critical inhibitory site in an energy-producing enzyme, which can lead to rational design of antibiotics. We succeeded in identifying an antibiotic, which is effective against a super drug-resistant strain of Neisseria gonorrhoeae. (published in Nat commun. Doi. 10.1038/s41467-022-34771-y, https://www.eurekalert.org/news-releases/973963) Specific research projects Understanding the molecular mechanism modulating the activity of mitochondrial cytochrome coxidase Structure-based drug design of an allosteric modulator of cytochrome coxidase to treat mitochondrial diseases, heart failure, and infectious diseases Identification of a novel molecule playing a pivotal role in myocardial inflammation Development of novel diagnostic tools and therapeutics for intracranial aneurysm Publication Nishida Y, Yanagisawa S, Morita R, Shigematsu H, Shinzawa-Itoh K, Yuki H, Ogasawara S, Yamazaki S, Nagao T, Iwamoto T, Nakabayashi C, Qaqorh T, Takahashi Y, Matsumura W, Kamiya K, Harada R, Mizuno N, Kumasaka T, Murata T, Muramoto K, Tosha T, Shiro Y, Honma T, Shigeta Y, Kubo M, Takashima S, Shintani Y# .Conserved allostery buried inside mitochondrial heme-copper oxidases can generate novel antibiotics. Nat commun. 2022;13(1):7591. Yashirogi S, Nagao T, Nishida Y, Takahashi Y, Tasneem Q, Yazawa I, Katayama T, Kioka H, Matsui TS, Saito S, Masumura Y, Tsukamoto O, Kato H, Ueda H, Yamaguchi O, Yashiro K, Yamazaki S, Takashima S, Shintani Y # . AMPK regulates cell shape of cardiomyocytes by modulating turnover of microtubules through CLIP-170. EMBO Rep. 2021;22(1):e50949. Nagao T, Shintani Y#, Hayashi T, Kioka H, Kato H, Nishida Y, Yamazaki S, Tsukamoto O, Yashirogi S, Yazawaa I, Asano Y, Shinzawa-Itohe K, Imamura H, Suzuki T, Suzuki T, Goto Y, Takashima S. Higd1a improves respiratory function in the models of mitochondrial disorder. FASEB J. 2020;34(1):1859-1871. 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, Takashima S.. Mutant KCNJ3 and KCNJ5 Potassium Channels as Novel Molecular Targets in Bradyarrhythmias and Atrial Fibrillation. Circulation. 2019;139:2157-2169. Shiraishi M, Shintani Y , Shintani Y, Ishida H, Saba R, Yamaguchi A, Adachi H, Yashiro K, Suzuki K. Alternatively activated macrophages determine repair of the infarcted adult murine heart. J Clin Invest. 2016;126(6):2151-66. Hayashi T, Asano Y, Shintani Y , Aoyama H, Kioka H, Tsukamoto O, Hikita M, Shinzawa-Itoh K, Takafuji K, Higo S, Kato H, Yamazaki S, Matsuoka K, Nakano A, Asanuma H, Asakura M, Minamino T, Goto Y-I, Ogura T, Kitakaze M, Komuro I, Sakata Y, Tsukihara T, Yoshikawa S, Takashima S. Higd1a is a positive regulator of cytochrome c oxidase. Proc Natl Acad Sci USA. 2015;112:1553–1558. Shintani Y#, Drexler HC, Kioka H, Terracciano CM, Coppen SR, Imamura H, Akao M, Nakai J, Wheeler AP, Higo S, Nakayama H, Takashima S, Yashiro K, Suzuki K#. Toll-like receptor 9 protects non-immune cells from stress by modulating mitochondrial ATP synthesis through the inhibition of SERCA2. EMBO Rep. 2014;15:438–445. Shintani Y# , Kapoor A, Kaneko M, Smolenski RT, D'Acquisto F, Coppen SR, Harada-Shoji N, Lee HJ, Thiemermann C, Takashima S, Yashiro K, Suzuki K#. TLR9 mediates cellular protection by modulating energy metabolism in cardiomyocytes and neurons. Proc Natl Acad Sci USA. 2013; 110:5109–5114. Nakano A, Kato H, Watanabe T, Min K-D, Yamazaki S, Asano Y, Seguchi O, Higo S, Shintani Y, Asanuma H, Asakura M, Minamino T, Kaibuchi K, Mochizuki N, Kitakaze M, Takashima S. AMPK controls the speed of microtubule polymerization and directional cell migration through CLIP-170 phosphorylation. Nat Cell Biol. 2010; 12:583–590. Kitakaze M, Asakura M, Kim J, Shintani Y, Asanuma H, Hamasaki T, Seguchi O, Myoishi M, Minamino T, Ohara T, Nagai Y, Nanto S, Watanabe K, Fukuzawa S, Hirayama A, Nakamura N, Kimura K, Fujii K, Ishihara M, Saito Y, Tomoike H, Kitamura S, J-WIND investigators. Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): two randomised trials. Lancet. 2007; 370:1483–1493. Seguchi O, Takashima S, Yamazaki S, Asakura M, Asano Y, Shintani Y, Wakeno M, Minamino T, Kondo H, Furukawa H, Nakamaru K, Naito A, Takahashi T, Ohtsuka T, Kawakami K, Isomura T, Kitamura S, Tomoike H, Mochizuki N, Kitakaze M. A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart. J Clin Invest. 2007; 117:2812–2824. Shintani Y, Takashima S, Asano Y, Kato H, Liao Y, Yamazaki S, Tsukamoto O, Seguchi O, Yamamoto H, Fukushima T, Sugahara K, Kitakaze M, Hori M. Glycosaminoglycan modification of neuropilin-1 modulates VEGFR2 signaling. The EMBO Journal. 2006; 25:3045–3055. # corresponding authorlast updated : 2023/10/06 (Corporate number:3120905003033) 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan TEL：81-6-6170-1070 Access Copyright © National Cerebral and Cardiovascular Center All rights reserved. Site setting Font-size Normal Large Background White Black Japanese English