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Biomolecular Networks Laboratories

Laboratory of Medical Biochemistry

Prof. TAKASHIMA Seiji Prof. TAKASHIMA Seiji

Keywords:

Drug discovery, Treatment of diseases, Protein biochemistry, Single cell transcriptome

Developing therapeutics that will change the course of history

Based on the achievements of identifying important factors using various assay systems, we are conducting research utilizing creative protein biochemical techniques. Based on the close relationship between research and clinical laboratories, we have found new drug discovery targets and are promoting first-in-class drug breakthroughs. Currently, the development of eight kinds of drug discovery candidates, such as drugs in the target identification stage, drugs currently being screened, drugs in the compound development stage, in vivo POC stage, and clinical trial stage; etc. are being pursued in parallel. We focus on specific proteins by using advanced antibody production technology, artificial amino acid introduction protein synthesis, an original pretreated mass spectrometer, structural analyses; etc. We are collaborating with a number of pharmaceutical companies as well. Using our abundant research funds, we are seriously working on drug discovery development that targets cardiovascular diseases, psychiatric disorders, metabolic diseases, and cancer. The drugs we produce will alter the course of current medical understanding. Come and join our vision.

Identification of Regulatory Proteins for ATP Production Using Sensitive in vivo ATP Production Assay

Members

TAKASHIMA Seiji  (Professor) takasima[at]cardiology.med.osaka-u.ac.jp
MATSUOKA Ken (Associate Professor) kmatsuoka[at]medbio.med.osaka-u.ac.jp
KATO Hisakazu (Assistant Professor, Graduate School of Medicine) katohisa[at]medbio.med.osaka-u.ac.jp
TAKADA Eri (Technical Staff, Graduate School of Medicine)  
KISHIMOTO Mayumi (Technical Staff, Graduate School of Medicine)  
   
   
   
   

You could probably reach more information of individual researchers by Research Map and researcher's search of Osaka-U.

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Q&A

What is your hot research topic?
  1. The treatment of mitochondrial diseases through the direct activation of oxidative phosphorylation enzymes.
  2. The treatment of heart failure and skeletal muscle diseases directly with sarcomere activators.
  3. Drug development using a multi-screening system concerning the life span of protein.
  4. Elucidation of gene expression control mechanism and gene therapy
What is your breakthrough or research progress in the last 5 years?
Increase in new drug discovery pipeline and progress in each pipeline
What kind of background do your lab members have?
Half of both instructors and students are composed of Medical Doctor.
Do you collaborate with other institutions and universities?
Joint research is being conducted with academia and the business sectors
What kind of careers do your Lab's alumni go on to?
Doctors, company researchers.
How do you develop your research?
To produce first-in-class drug development.

Research Highlights

Publications (Research Articles, Reviews, Books)

2020

Hayashi K, Teramoto R, Nomura A, Asano Y, Beerens M, Kurata Y, Kobayashi I, Fujino N, Furusho H, Sakata K, Onoue K, Chiang DY, Kiviniemi TO, Buys E, Sips P, Burch ML, Zhao Y, Kelly AE, Namura M, Kita Y, Tsuchiya T, Kaku B, Oe K, Takeda Y, Konno T, Inoue M, Fujita T, Kato T, Funada A, Tada H, Hodatsu A, Nakanishi C, Sakamoto Y, Tsuda T, Nagata Y, Tanaka Y, Okada H, Usuda K, Cui S, Saito Y, MacRae CA, Takashima S, Yamagishi M, Kawashiri MA, Takamura M

Impact of functional studies on exome sequence variant interpretation in early-onset cardiac conduction system diseases.

Cardiovasc. Res. cvaa010  2020 PMID:31977013 DOI:10.1093/cvr/cvaa010

Kioka H, Kato H, Fujita T, Asano Y, Shintani Y, Yamazaki S, Tsukamoto O, Imamura H, Kogo M, Kitakaze M, Sakata Y, Takashima S

In vivo real-time ATP imaging in zebrafish hearts reveals G0s2 induces ischemic tolerance.

Faseb J. 34(2):2041-2054  2020 PMID:31916304 DOI:10.1096/fj.201901686R

Shimizu A, Zankov DP, Sato A, Komeno M, Toyoda F, Yamazaki S, Makita T, Noda T, Ikawa M, Asano Y, Miyashita Y, Takashima S, Morita H, Ishikawa T, Makita N, Hitosugi M, Matsuura H, Ohno S, Horie M, Ogita H

Identification of transmembrane protein 168 mutation in familial Brugada syndrome.

Faseb J. 34(5):6399-6417  2020 PMID:32175648 DOI:10.1096/fj.201902991R

Nagao T, Shintani Y, Hayashi T, Kioka H, Kato H, Nishida Y, Yamazaki S, Tsukamoto O, Yashirogi S, Yazawa I, Asano Y, Shinzawa-Itoh K, Imamura H, Suzuki T, Suzuki T, Goto YI, Takashima S

Higd1a improves respiratory function in the models of mitochondrial disorder

Faseb J. 34:1859-1871  2020 PMID:31914602 DOI:10.1096/fj.201800389R

2019

Tsukamoto O

Direct Sarcomere Modulators Are Promising New Treatments for Cardiomyopathies

Int. J. Mol. Sci. 21(1):226  2019 PMID:31905684 DOI:10.3390/ijms21010226

Takahama H, Asanuma H, Tsukamoto O, Ito S, Kitakaze M

Endogenously released adenosine causes pulmonary vasodilation during the acute phase of pulmonary embolization in dogs

Int J Cardiol Heart Vasc 24:100396  2019 PMID:31334333 DOI:10.1016/j.ijcha.2019.100396

Asanuma H, Chung H, Ito S, Min KD, Ihara M, Takahama H, Funayama M, Imazu M, Fukuda H, Ogai A, Asano Y, Minamino T, Takashima S, Morita T, Sugimachi M, Asakura M, Kitakaze M

AST-120, an Adsorbent of Uremic Toxins, Improves the Pathophysiology of Heart Failure in Conscious Dogs.

Cardiovasc. Drugs Ther. 33(3):277-286  2019 PMID:30903544 DOI:10.1007/s10557-019-06875-z

Takahashi Y, Saito S, Kioka H, Araki R, Asano Y, Takashima S, Sakata Y, Yoshioka Y

Mouse skeletal muscle creatine chemical exchange saturation transfer (CrCEST) imaging at 11.7T MRI.

J. Magn. Reson. Imaging 51(2):563-570  2019 PMID:31228359 DOI:10.1002/jmri.26844

Kamikubo K, Kato H, Kioka H, Yamazaki S, Tsukamoto O, Nishida Y, Asano Y, Imamura H, Kawahara H, Shintani Y, Takashima S

A molecular triage process mediated by RING finger protein 126 and BCL2-associated athanogene 6 regulates degradation of G0/G1 switch gene 2.

J. Biol. Chem. 294(40):14562-14573  2019 PMID:31371451 DOI:10.1074/jbc.RA119.008544

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 139(18):2157-2169  2019 PMID:30764634 DOI:10.1161/CIRCULATIONAHA.118.036761

Takahashi Y, Kioka H, Shintani Y, Ohki A, Takashima S, Sakata Y, Higuchi T, Saito S

Detection of increased intracerebral lactate in a mouse model of Leigh syndrome using proton MR spectroscopy.

Magn. Reson. Imaging 58:38-43  2019 PMID:30668983 DOI:10.1016/j.mri.2019.01.010

Hodatsu A, Fujino N, Uyama Y, Tsukamoto O, Imai-Okazaki A, Yamazaki S, Seguchi O, Konno T, Hayashi K, Kawashiri MA, Asano Y, Kitakaze M, Takashima S, Yamagishi M

Impact of cardiac myosin light chain kinase gene mutation on development of dilated cardiomyopathy.

ESC Heart Fail. 6(2):406-415  2019 PMID:30690923 DOI:10.1002/ehf2.12410

2018

Tsuchida S, Matsuzaki T, Yamato M, Okuda K, Fu HY, Araki R, Sanada S, Asanuma H, Asano Y, Asakura M, Hao H, Takashima S, Kitakaze M, Sakata Y, Mekada E, Minamino T

Anti-HB-EGF Antibody-Mediated Delivery of siRNA to Atherosclerotic Lesions in Mice.

Int. Heart J. 59(6):1425-1431  2018 PMID:30393262 DOI:10.1536/ihj.17-644

Kobayashi K, Ichihara Y, Tano N, Fields L, Murugesu N, Ito T, Ikebe C, Lewis F, Yashiro K, Shintani Y, Uppal R, Suzuki K

Fibrin Glue-aided, Instant Epicardial Placement Enhances the Efficacy of Mesenchymal Stromal Cell-Based Therapy for Heart Failure.

Sci Rep 21;8(1):9448  2018 PMID:29930312 DOI:10.1038/s41598-018-27881-5

Mori D, Matsui I, Shimomura A, Hashimoto N, Matsumoto A, Shimada K, Yamaguchi S, Oka T, Kubota K, Yonemoto S, Sakaguchi Y, Takahashi A, Shintani Y, Takashima S, Takabatake Y, Hamano T, Isaka Y

Protein carbamylation exacerbates vascular calcification.

Kidney Int. 94(1):72-90  2018 PMID:29716796 DOI:10.1016/j.kint.2018.01.033

Tobita T, Nomura S, Fujita T, Morita H, Asano Y, Onoue K, Ito M, Imai Y, Suzuki A, Ko T, Satoh M, Fujita K, Naito AT, Furutani Y, Toko H, Harada M, Amiya E, Hatano M, Takimoto E, Shiga T, Nakanishi T, Sakata Y, Ono M, Saito Y, Takashima S, Hagiwara N, Aburatani H, Komuro I

Genetic basis of cardiomyopathy and the genotypes involved in prognosis and left ventricular reverse remodeling.

Sci Rep 8(1):1998  2018 PMID:29386531 DOI:10.1038/s41598-018-20114-9

2017

Ikeda K, Kinoshita M, Kayama H, Nagamori S, Kongpracha P, Umemoto E, Okumura R, Kurakawa T, Murakami M, Mikami N, Shintani Y, Ueno S, Andou A, Ito M, Tsumura H, Yasutomo K, Ozono K, Takashima S, Sakaguchi S, Kanai Y, Takeda K

Slc3a2 Mediates Branched-Chain Amino-Acid-Dependent Maintenance of Regulatory T Cells.

Cell Reports 21(7):1824-1838  2017 PMID:29141216 DOI:10.1016/j.celrep.2017.10.082

Asanuma H, Sanada S, Yoshitomi T, Sasaki H, Takahama H, Ihara M, Takahama H, Shinozaki Y, Mori H, Asakura M, Nakano A, Sugimachi M, Asano Y, Minamino T, Takashima S, Nagasaki Y, Kitakaze M

Novel Synthesized Radical-Containing Nanoparticles Limit Infarct Size Following Ischemia and Reperfusion in Canine Hearts.

Cardiovasc. Drugs Ther. 31(5-6):501-510  2017 PMID:29101507 DOI:10.1007/s10557-017-6758-6

Nagata Y, Yamagishi M, Konno T, Nakanishi C, Asano Y, Ito S, Nakajima Y, Seguchi O, Fujino N, Kawashiri MA, Takashima S, Kitakaze M, Hayashi K

Heat Failure Phenotypes Induced by Knockdown of DAPIT in Zebrafish: A New Insight into Mechanism of Dilated Cardiomyopathy.

Auris Nasus Larynx 7(1):17417  2017 PMID:29234032 DOI:10.1038/s41598-017-17572-y

Kotani Y, Morito D, Sakata K, Ainuki S, Sugihara M, Hatta T, Iemura SI, Takashima S, Natsume T, Nagata K

Alternative exon skipping biases substrate preference of the deubiquitylase USP15 for mysterin/RNF213, the moyamoya disease susceptibility factor.

Autophagy 7:44293  2017 PMID:28276505 DOI:10.1038/srep44293

Ishizu T, Higo S, Masumura Y, Kohama Y, Shiba M, Higo T, Shibamoto M, Nakagawa A, Morimoto S, Takashima S, Hikoso S, Sakata Y

Targeted Genome Replacement via Homology-directed Repair in Non-dividing Cardiomyocytes.

Sci Rep 7(1):9363  2017 PMID:28839205 DOI:10.1038/s41598-017-09716-x

Tsukamoto O, Kitakaze M

Radiation-induced HFpEF model as a potential tool for the exploration of novel therapeutic targets.

Am. J. Physiol.-Heart Circul. Physiol. 313(2):H323-H325  2017 PMID:28626077 DOI:10.1152/ajpheart.00307.2017

2016

Kita A, Hino N, Higashi S, Hirota K, Narumi R, Adachi J, Takafuji K, Ishimoto K, Okada Y, Sakamoto K, Tomonaga T, Takashima S, Mizuguchi H, Doi T

Adenovirus vector-based incorporation of a photo-cross-linkable amino acid into proteins in human primary cells and cancerous cell lines.

Sci Rep 6:36946  2016 PMID:27833131 DOI:10.1038/srep36946

Campbell NG, Kaneko M, Shintani Y, Narita T, Sawhney V, Coppen SR, Yashiro K, Mathur A, Suzuki K

Cell Size Critically Determines Initial Retention of Bone Marrow Mononuclear Cells in the Heart after Intracoronary Injection: Evidence from a Rat Model.

PLoS One 11(7):e0158232  2016 PMID:27380410 DOI:10.1371/journal.pone.0158232

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. 126(6):2151-66  2016 PMID:27140396 DOI:10.1172/JCI85782

Nishida Y, Ikeya T, Mikawa T, Inoue J, Ito Y, Shintani Y, Masui R , Kuramitsu S, Takashima S

A specific single-stranded DNA induces a distinct conformational changecrossmark in the nucleoid-associated protein HU

Biochemistry and Biophysics Reports 8:318-324  2016 PMID:28955971 DOI:10.1016/j.bbrep.2016.09.014

Tano N, Kaneko M, Ichihara Y, Ikebe C, Coppen SR, Shiraishi M, Shintani Y, Yashiro K, Warrens A, Suzuki K

Allogeneic Mesenchymal Stromal Cells Transplanted Onto the Heart Surface Achieve Therapeutic Myocardial Repair Despite Immunologic Responses in Rats.

J. Am. Heart Assoc. 5(2):e002815  2016 PMID:26896478 DOI:10.1161/JAHA.115.002815

Okuda K, Fu HY, Matsuzaki T, Araki R, Tsuchida S, Thanikachalam PV, Fukuta T, Asai T, Yamato M, Sanada S, Asanuma H, Asano Y, Asakura M, Hanawa H, Hao H, Oku N, Takashima S, Kitakaze M, Sakata Y, Minamino T

Targeted Therapy for Acute Autoimmune Myocarditis with Nano-Sized Liposomal FK506 in Rats.

PLoS One 1(8):e0160944  2016 PMID:27501378 DOI:10.1371/journal.pone.0160944

Ito S, Asakura M, Liao Y, Min KD, Takahashi A, Shindo K, Yamazaki S, Tsukamoto O, Asanuma H, Mogi M, Horiuchi M, Asano Y, Sanada S, Minamino T, Takashima S, Mochizuki N, Kitakaze M

Identification of the Mtus1 Splice Variant as a Novel Inhibitory Factor Against Cardiac Hypertrophy.

J. Am. Heart Assoc. 5(7):e003521  2016 PMID:27385424 DOI:10.1161/JAHA.116.003521

Masumura Y, Higo S, Asano Y, Kato H, Yan Y, Ishino S, Tsukamoto O, Kioka H, Hayashi T, Shintani Y, Yamazaki S, Minamino T, Kitakaze M, Komuro I, Takashima S, Sakata Y

Btg2 is a Negative Regulator of Cardiomyocyte Hypertrophy through a Decrease in Cytosolic RNA.

Sci Rep 6:28592  2016 PMID:27346836 DOI:10.1038/srep28592

Kanzaki M, Asano Y, Ishibashi-Ueda H, Oiki E, Nishida T, Asanuma H, Kato H, Oka T, Ohtani T, Tsukamoto O, Higo S, Kioka H, Matsuoka K, Sawa Y, Komuro I, Kitakaze M, Takashima S, Sakata Y

A Development of Nucleic Chromatin Measurements as a New Prognostic Marker for Severe Chronic Heart Failure.

PLoS One 11(2):e0148209  2016 PMID:26845691 DOI:10.1371/journal.pone.0148209

2015

Kokkinopoulos I, Ishida H, Saba R, Ruchaya P, Cabrera C, Struebig M, Barnes M, Terry A, Kaneko M, Shintani Y, Coppen S, Shiratori H, Ameen T, Mein C, Hamada H, Suzuki K, Yashiro K

Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.

PLoS One 10(10):e0140831  2015 PMID:26469858 DOI:10.1371/journal.pone.0140831

Our ideal candidate (as a graduate student)

We are looking for a highly motivated person to work on our research topics as our lab member. Our lab welcomes the person who loves taking care of creatures, hand working and handcraft too. Any kind of background (such as your expertise or major) is available.

Contact

Laboratory of Medical Biochemistry, Graduate School of Frontier Biosciences, Osaka University,
2-2 Yamadaoka, Suita, Osaka 565-0871 Japan.

TEL:+81-6-6879-3492

E-mail: takasima[at]cardiology.med.osaka-u.ac.jp (Prof. Seiji Takashima)

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