Education 【 display / non-display 】

Education 【 display / non-display 】

• 2013

  -

  2017

  Sapporo Medical University   医学研究科博士課程 修了  

• 2005

  -

  2011

  Sapporo Medical University   医学部医学科 卒業  

Degree 【 display / non-display 】

Degree 【 display / non-display 】

• 2017.03   札幌医科大学大学院医学研究科   博士（医学）

Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2023.06

  -

  Now

  札幌医科大学医学部   薬理学講座   助教

• 2023.06

  -

  Now

  札幌医科大学医学部   循環器・腎臓・代謝内分泌内科学講座   助教

• 2018.10

  -

  2023.05

  米国ノースウエスタン大学医学部   ファインバーグ心臓血管腎臓研究所   博士研究員

• 2018.04

  -

  2018.09

  北海道立江差病院   循環器内科   医長

• 2017.04

  -

  2018.03

  社会医療法人母恋 天使病院   循環器内科   診療医

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Professional Memberships 【 display / non-display 】

Professional Memberships 【 display / non-display 】

• 2024.08

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  Now

  The Molecular Biology Society of Japan

• 2023.08

  -

  Now

  U-45 International Society for Heart Research

• 2023.08

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  Now

  日本薬理学会

• 2018.02

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  Now

  American Heart Association

• 2017.05

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  Now

  日本心不全学会

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Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Pathobiochemistry   Protein glycosylation

• Life sciences   Cardiology   心不全

• Life sciences   Medical biochemistry   Metabolomics analysis

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University School of Medicine   Department of Pharmacology   Assistant professor  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• HFpEF

• Heart failure

• Glycosylation

• Diabetes Mellitus

• Endothelial cell

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Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Resveratrol promotes autophagosome elimination via SIRT1 in cardiomyocytes.

  Atsushi Kuno, Ryusuke Hosoda, Yukika Saga, Naotoshi Iwahara, Yuki Tatekoshi, Ryo Numazawa, Yoshiyuki Horio

  Journal of Pharmacological Sciences ( Elsevier BV )   2024.11

  DOI

• Human induced pluripotent stem cell-derived cardiomyocytes to study inflammation-induced aberrant calcium transient.

  Yuki Tatekoshi, Chunlei Chen, Jason Solomon Shapiro, Hsiang-Chun Chang, Malorie Blancard, Davi M Lyra-Leite, Paul W Burridge, Matthew Feinstein, Richard D'Aquila, Priscilla Hsue, Hossein Ardehali

  eLife   13  2024.09  [International journal]

  　View Summary

  Heart failure with preserved ejection fraction (HFpEF) is commonly found in persons living with HIV (PLWH) even when antiretroviral therapy suppresses HIV viremia. However, studying this condition has been challenging because an appropriate animal model is not available. In this article, we studied calcium transient in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in culture to simulate the cardiomyocyte relaxation defect noted in PLWH and HFpEF and assess whether various drugs have an effect. We show that treatment of hiPSC-CMs with inflammatory cytokines (such as interferon-γ or TNF-α) impairs their Ca2+ uptake into sarcoplasmic reticulum and that SGLT2 inhibitors, clinically proven as effective for HFpEF, reverse this effect. Additionally, treatment with mitochondrial antioxidants (like mito-Tempo) and certain antiretrovirals resulted in the reversal of the effects of these cytokines on calcium transient. Finally, incubation of hiPSC-CMs with serum from HIV patients with and without diastolic dysfunction did not alter their Ca2+-decay time, indicating that the exposure to the serum of these patients is not sufficient to induce the decrease in Ca2+ uptake in vitro. Together, our results indicate that hiPSC-CMs can be used as a model to study molecular mechanisms of inflammation-mediated abnormal cardiomyocyte relaxation and screen for potential new interventions.

  DOI PubMed

• Mitochondria regulate proliferation in adult cardiac myocytes

  Gregory B. Waypa, Kimberly A. Smith, Paul T. Mungai, Vincent J. Dudley, Kathryn A. Helmin, Benjamin D. Singer, Clara Bien Peek, Joseph Bass, Lauren Nelson, Sanjiv J. Shah, Gaston Ofman, J. Andrew Wasserstrom, William A. Muller, Alexander V. Misharin, G.R. Scott Budinger, Hiam Abdala-Valencia, Navdeep S. Chandel, Danijela Dokic, Elizabeth Bartom, Shuang Zhang, Yuki Tatekoshi, Amir Mahmoodzadeh, Hossein Ardehali, Edward B. Thorp, Paul T. Schumacker

  Journal of Clinical Investigation ( American Society for Clinical Investigation )  134 ( 13 )  2024.05  [Refereed]

  DOI

• Downregulation of Mitochondrial Fusion Protein Expression Affords Protection from Canonical Necroptosis in H9c2 Cardiomyoblasts

  Yuki Toda, Sang-Bing Ong, Toshiyuki Yano, Atsushi Kuno, Hidemichi Kouzu, Tatsuya Sato, Wataru Ohwada, Yuki Tatekoshi, Toshifumi Ogawa, Masaki Shimizu, Masaya Tanno, Masato Furuhashi

  International Journal of Molecular Sciences ( MDPI AG )  25 ( 5 ) 2905 - 2905  2024.03  [Refereed]

  　View Summary

  Necroptosis, a form of necrosis, and alterations in mitochondrial dynamics, a coordinated process of mitochondrial fission and fusion, have been implicated in the pathogenesis of cardiovascular diseases. This study aimed to determine the role of mitochondrial morphology in canonical necroptosis induced by a combination of TNFα and zVAD (TNF/zVAD) in H9c2 cells, rat cardiomyoblasts. Time-course analyses of mitochondrial morphology showed that mitochondria were initially shortened after the addition of TNF/zVAD and then their length was restored, and the proportion of cells with elongated mitochondria at 12 h was larger in TNF/zVAD-treated cells than in non-treated cells (16.3 ± 0.9% vs. 8.0 ± 1.2%). The knockdown of dynamin-related protein 1 (Drp1) and fission 1, fission promoters, and treatment with Mdivi-1, a Drp-1 inhibitor, had no effect on TNF/zVAD-induced necroptosis. In contrast, TNF/zVAD-induced necroptosis was attenuated by the knockdown of mitofusin 1/2 (Mfn1/2) and optic atrophy-1 (Opa1), proteins that are indispensable for mitochondrial fusion, and the attenuation of necroptosis was not canceled by treatment with Mdivi-1. The expression of TGFβ-activated kinase (TAK1), a negative regulator of RIP1 activity, was upregulated and the TNF/zVAD-induced RIP1-Ser166 phosphorylation, an index of RIP1 activity, was mitigated by the knockdown of Mfn1/2 or Opa1. Pharmacological TAK1 inhibition attenuated the protection afforded by Mfn1/2 and Opa1 knockdown. In conclusion, the inhibition of mitochondrial fusion increases TAK1 expression, leading to the attenuation of canonical necroptosis through the suppression of RIP1 activity.

  DOI

• Role of AMP deaminase in diabetic cardiomyopathy

  Tetsuji Miura, Hidemichi Kouzu, Masaya Tanno, Yuki Tatekoshi, Atsushi Kuno

  Molecular and Cellular Biochemistry ( Springer Science and Business Media LLC )   2024.02  [Refereed]

  DOI

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• Administration of Nicotinamide Mononucleotide, a Precursor of NAD+, Attenuates Doxorubicin-induced Cardiotoxicity and Renal Tubular Injury in Mice(タイトル和訳中)

  齊藤 圭司, 細田 隆介, 嵯峨 幸夏, 舘越 勇輝, 久野 篤史

  日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  88回   PJ114 - 4  2024.03

• Impact of Mitochondrial Dynamics on Necroptosis in Cardiomyocytes(タイトル和訳中)

  戸田 悠貴, 矢野 俊之, 久野 篤史, 丹野 雅也, 神津 英至, 佐藤 達也, 大和田 渉, 舘越 勇輝, 小川 俊史, 清水 将輝, 古橋 眞人

  日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  88回   PJ080 - 3  2024.03

• DNA damage and nuclear morphological changes in cardiac hypertrophy are mediated by SNRK through actin depolymerization.

  Paulina Stanczyk, Yuki Tatekoshi, Jason S Shapiro, Krithika Nayudu, Yihan Chen, Zachary Zilber, Matthew Schipma, Adam De Jesus, Amir Mahmoodzadeh, Ashley Akrami, Hsiang-Chun Chang, Hossein Ardehali

  bioRxiv : the preprint server for biology    2023.07  [International journal]

  Authorship：   Lead author

  Internal/External technical report, pre-print, etc.  

  　View Summary

  BACKGROUND: Proper nuclear organization is critical for cardiomyocyte (CM) function, as global structural remodeling of nuclear morphology and chromatin structure underpins the development and progression of cardiovascular disease. Previous reports have implicated a role for DNA damage in cardiac hypertrophy, however, the mechanism for this process is not well delineated. AMPK family of proteins regulate metabolism and DNA damage response (DDR). Here, we examine whether a member of this family, SNF1-related kinase (SNRK), which plays a role in cardiac metabolism, is also involved in hypertrophic remodeling through changes in DDR and structural properties of the nucleus. METHODS: We subjected cardiac specific (cs)- Snrk -/- mice to trans-aortic banding (TAC) to assess the effect on cardiac function and DDR. In parallel, we modulated SNRK in vitro and assessed its effects on DDR and nuclear parameters. We also used phospho-proteomics to identify novel proteins that are phosphorylated by SNRK. Finally, co-immunoprecipitation (co-IP) was used to verify Destrin (DSTN) as the binding partner of SNRK that modulates its effects on the nucleus and DDR. RESULTS: cs- Snrk -/- mice display worse cardiac function and cardiac hypertrophy in response to TAC, and an increase in DDR marker pH2AX in their hearts. Additionally, in vitro Snrk knockdown results in increased DNA damage and chromatin compaction, along with alterations in nuclear flatness and 3D volume. Phospho-proteomic studies identified a novel SNRK target, DSTN, a member of F-actin depolymerizing factor (ADF) proteins that directly binds to and depolymerize F-actin. SNRK binds to DSTN, and DSTN downregulation reverses excess DNA damage and changes in nuclear parameters, in addition to cellular hypertrophy, with SNRK knockdown. We also demonstrate that SNRK knockdown promotes excessive actin depolymerization, measured by the increased ratio of globular (G-) actin to F-actin. Finally, Jasplakinolide, a pharmacological stabilizer of F-actin, rescues the increased DNA damage and aberrant nuclear morphology in SNRK downregulated cells. CONCLUSIONS: These results indicate that SNRK is a key player in cardiac hypertrophy and DNA damage through its interaction with DSTN. This interaction fine-tunes actin polymerization to reduce DDR and maintain proper CM nuclear shape and morphology. CLINICAL PERSPECTIVE: What is new? Animal hearts subjected to pressure overload display increased SNF1-related kinase (SNRK) protein expression levels and cardiomyocyte specific SNRK deletion leads to aggravated myocardial hypertrophy and heart failure.We have found that downregulation of SNRK impairs DSTN-mediated actin polymerization, leading to maladaptive changes in nuclear morphology, higher DNA damage response (DDR) and increased hypertrophy. What are the clinical implications? Our results suggest that disruption of DDR through genetic loss of SNRK results in an exaggerated pressure overload-induced cardiomyocyte hypertrophy.Targeting DDR, actin polymerization or SNRK/DSTN interaction represent promising therapeutic targets in pressure overload cardiac hypertrophy.

  DOI PubMed

• Temporal Trends in Mortality Attributable to Heart Failure between 2005 and 2019: Insights from Japanese Vital Statistics(タイトル和訳中)

  田中 仁啓, 舘越 勇輝, 藤本 恒, 夜久 英憲, カーン サディヤ, グリーンランド フィリップ

  日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  87回   OJ54 - 5  2023.03

• SIRT2 inhibition protects against cardiac hypertrophy and heart failure.

  Xiaoyan Yang, Hsiang-Chun Chang, Yuki Tatekoshi, Maryam Balibegloo, Rongxue Wu, Chunlei Chen, Tatsuya Sato, Jason Shapiro, Hossein Ardehali

  bioRxiv : the preprint server for biology    2023.01  [International journal]

  Authorship：   Lead author

  Internal/External technical report, pre-print, etc.  

  　View Summary

  Sirtuins (SIRT) exhibit deacetylation or ADP-ribosyltransferase activity and regulate a wide range of cellular processes in the nucleus, mitochondria and cytoplasm. The role of the only sirtuin that resides in the cytoplasm, SIRT2, in the development of heart failure (HF) and cardiac hypertrophy is not known. In this paper, we show that the hearts of mice with deletion of Sirt2 ( Sirt2 -/- ) display improved cardiac function after ischemia-reperfusion (I/R) and pressure overload (PO), suggesting that SIRT2 exerts maladaptive effects in the heart in response to stress. Similar results were obtained in mice with cardiomyocyte-specific Sirt2 deletion. Mechanistic studies suggest that SIRT2 modulates cellular levels and activity of nuclear factor (erythroid-derived 2)-like 2 (NRF2), which results in reduced expression of antioxidant proteins. Deletion of Nrf2 in the hearts of Sirt2 -/- mice reversed protection after PO. Finally, treatment of mouse hearts with a specific SIRT2 inhibitors reduces cardiac size and attenuates cardiac hypertrophy in response to PO. These data indicate that SIRT2 has detrimental effects in the heart and plays a role in the progression of HF and cardiac hypertrophy, which makes this protein a unique member of the SIRT family. Additionally, our studies provide a novel approach for treatment of cardiac hypertrophy by targeting SIRT2 pharmacologically, providing a novel avenue for the treatment of this disorder.

  DOI PubMed

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Industrial Property Rights 【 display / non-display 】

Industrial Property Rights 【 display / non-display 】

• Methods and compositions for treatment of heart failure with preserved ejection fraction

  Yuki Tatekoshi, Hossein Ardehali

  Patent

Awards 【 display / non-display 】

Awards 【 display / non-display 】

• UJA Outstanding Paper Award 2024 Special Award

  2024.05   United Japanese Researchers Around the World   DNA Damage and Nuclear Morphological Changes in Cardiac Hypertrophy Are Mediated by SNRK Through Actin Depolymerization

  Winner： Yuki Tatekoshi

• CPIS award

  2024.03   The Japanese Circulation Society   Hexokinase-1 mitochondrial dissociation and protein O-GlcNAcylation drive heart failure with preserved ejection fraction

• Best of AHA Specialty Conference: BCVS

  2022.11   American Heart Association Scientific Session 2022  

• Best Poster Award

  2016.08   ESC congress 2016 (Rome)  

• 第三回新人賞

  2013.10   日本超音波医学会  

Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• 内皮細胞が制御する耐糖能と5S-GlcNHexの新規糖尿病治療薬としての可能性

  Project Year :

  2024.08

  -

  2029.03

   

  舘越 勇輝

  Authorship： Principal investigator

• 内皮細胞が制御する耐糖能と新規糖尿病治療薬の開発

  Project Year :

  2024.08

  -

  2025.08

   

  舘越 勇輝

  Authorship： Principal investigator

• 血管内皮幹細胞の動態・機能解析に基づくHFpEFの新規治療法の探索

  Project Year :

  2024.07

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  2025.06

   

  舘越 勇輝

  Authorship： Principal investigator

• 心臓における血管内皮幹細胞の動態評価とHFpEFへの治療応用

  Project Year :

  2024.07

  -

  2025.05

   

  舘越 勇輝

  Authorship： Principal investigator

• Exploration of novel therapeutic approaches for HFpEF based on dynamic and functional analysis of vascular endothelial stem cells.

  Grant-in-Aid for Early-Career Scientists

  Project Year :

  2024.04

  -

  2027.03

   

  舘越 勇輝

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Presentations 【 display / non-display 】

Presentations 【 display / non-display 】

• SNRKが制御するアクチン重合・DNA損傷・心筋肥大

  舘越 勇輝  [Invited]

  UJA論文賞2024; オンライン授賞式 

  Presentation date： 2024.05

  Event date：

  2024.05

  　

  　

• Protein O-GlcNAcylation in Endothelial Cells Drives the Development of Heart Failure with Preserved Ejection Fraction

  Yuki Tatekoshi

  The 88th Annual Scientific Meeting of the Japanese Circulation Society 

  Presentation date： 2024.03

  Event date：

  2024.03

  　

  　

• UJA 留学のすゝめ2023 日本の科学技術を推進するネットワーク構築

   [Invited]

  第46回日本分子生物学会年会 

  Presentation date： 2023.12

  Event date：

  2023.12

  　

  　

• A novel mechanism in the pathogenesis of heart failure with preserved ejection fraction through hexokinase mitochondrial dislocation and substrate shuttling into the O-GlcNAcylation machinery

  Yuki Tatekoshi

  American Heart Association Scientific Sessions 2022 

  Presentation date： 2022.11

  Event date：

  2022.11

  　

  　

• Protein O-GlcNAcylation mediated by hexokinase mitochondrial localization underlies the pathogenesis of heart failure with preserved ejection fraction

  Yuki Tatekoshi

  Keystone symposia Heart failure: Mechanism and Therapies 

  Presentation date： 2022.10

  Event date：

  2022.09

  -

  2022.10

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Teaching Experience 【 display / non-display 】

Teaching Experience 【 display / non-display 】

• 臨床検査・薬理学  

  札幌医科大学  

  2024.05

  　

  　

   

• PBLチュートリアル  

  札幌医科大学  

  2024.04

  -

  2024.05

   

• 医学概論・医療総論1  

  札幌医科大学  

  2024.01

  　

  　

   

• 生理・薬理実習  

  札幌医科大学  

  2024.01

  　

  　

   

• 研究室 (基礎) 配属  

  札幌医科大学  

  2023.11

  -

  2023.12

   

Committee Memberships 【 display / non-display 】

Committee Memberships 【 display / non-display 】

• 2023.08

  -

  Now

    Section leader

• 2021.07

  -

  2023.05

    イリノイ州チーフディレクター

• 2021.07

  -

  2023.04

    Organizer

Academic Activities 【 display / non-display 】

Academic Activities 【 display / non-display 】

• Reviewer for Cardiovascular Diabetology

  Peer review

  Cardiovascular Diabetology  

  2024.09

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  Now

• Reviewer for Physiological Reports

  Peer review

  Physiological Reports  

  2024.06

  -

  Now

• 第88回日本循環器学会学術集会ポスターセッション（日本語） 54 「Heart Failure (Basic) 1」

  Academic society, research group, etc.

  日本循環器学会  

  2024.03

  　

  　

• Reviewer for the International Heart Journal

  Peer review

  International Heart Journal  

  2023.09

  -

  Now

• UJA論文賞

  Scientific advice/Review

  2021.07

  -

  2023.05

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