Updated on 2021/03/31

写真a

 
SHIMIZU Yuuki
 
Organization
Graduate School of Medicine Program in Integrated Medicine Internal Medicine Assistant Professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine Department of Medicine
Title
Assistant Professor

Degree 2

  1. 医学博士 ( 2013.3   名古屋大学 ) 

  2. 医学士 ( 2001.3   名古屋大学 ) 

Research Interests 9

  1. 血管生物学

  2. Angiogenesis

  3. Adipose derived regenerative cells

  4. 時間生物学

  5. cardio protection

  6. Regenerative medicine

  7. Lymphangiogenesis

  8. ミトコンドリア

  9. Translational research

Research Areas 1

  1. Life Science / Cardiology  / Cardiology

Research History 3

  1. Nagoya University   Graduate School of Medicine   Assistant Professor

    2020.4

  2. Nagoya University   Hospital, Hospital   Assistant professor of hospital

    2017.4 - 2020.3

  3. エモリー大学医学部   外科学・胸部外科   博士研究員

    2014.4 - 2017.3

Education 2

  1. Nagoya University   Graduate School, Division of Medical Sciences

    - 2013.3

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    Country: Japan

  2. Nagoya University   Faculty of Medicine

    - 2001.3

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    Country: Japan

Professional Memberships 11

  1. 日本内科学会

  2. 日本循環器学会

  3. 米国心臓協会

  4. BCVS

  5. 日本再生医療学会

  6. 時間生物学会

  7. 日本下肢救済・足病学会

  8. 日本血管生物医学会

  9. 日本リンパ学会

  10. International Society for Heart Research(ISHR)

  11. ESC   FESC

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Committee Memberships 1

  1. 日本循環器学会   予防委員会  

    2020.9   

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    Committee type:Academic society

Awards 6

  1. ATVB Travel Award for Young Investigators

    2016.11   ATVB  

  2. AHA scientific session 2015 Best of Basic Science Abstract

    2015.11  

  3. BCVS abstract travel grant 2015

    2015.11   BCVS  

  4. 米国心臓協会 博士研究員フェローシップ

    2015.7   米国心臓協会  

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    Award type:Award from international society, conference, symposium, etc. 

  5. 海外留学研究助成

    2014.4   万有財団  

  6. 日本循環器学会 東海支部 国際交流助成

    2011.11   日本循環器学会  

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Papers 28

  1. No influence on tumor growth by intramuscular injection of adipose-derived regenerative cells: safety evaluation of therapeutic angiogenesis with cell therapy Reviewed

    Junya Suzuki, Yuuki Shimizu, Kazuhito Tsuzuki, Zhongyue Pu, Shingo Narita, Shukuro Yamaguchi, Takeshi Katagiri, Etsuo Iwata, Tomohiro Masutomi, Yusuke Fujikawa, Rei Shibata, Toyoaki Murohara

    American Journal of Physiology-Heart and Circulatory Physiology   Vol. 320 ( 1 ) page: H447 - H457   2021.1

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:American Physiological Society  

    Therapeutic angiogenesis with autologous stem/progenitor cells is a promising novel strategy for treatment of severe ischemic diseases. Human clinical trials utilizing autologous adipose-derived regenerative cells (ADRCs) have not reported treatment-related critical adverse effects thus far. However, there is still a large knowledge gap whether treatment of ischemic diseases with angiogenic therapy using ADRCs would promote unfavorable angiogenesis associated with tumors in vivo. Herein, we addressed this clinical question using a mouse hind limb ischemia (HLI) and simultaneous remote tumor implantation model. C57BL/6J background wild-type mice were injected with murine B16F10 melanoma cells on their back, one day before ischemic surgery. These mice were subjected to surgical unilateral hindlimb ischemia, followed by ADRCs implantation or PBS injection into the hindlimb ischemic muscles on the next day. Intramuscular implantation of ADRCs enhanced tissue capillary density and blood flow examined by a laser Doppler blood perfusion analysis in hind limb. However, this therapeutic regimen for ischemic limb using ADRCs did not affect remote melanoma growth nor the density of its feeder artery, angiogenesis and lymphatic vessels compared to the PBS group. In addition, no distant metastases were detected in any of the mice regardless the group. In conclusion, local implantation of ADRCs promotes angiogenesis in response to tissue ischemia in the hind limb without promoting remote tumor growth and related angio/lymphangiogenesis. Therapeutic angiogenesis to the ischemic hind limb using ADRCs seems to be safe regarding remote tumor growth.

    DOI: 10.1152/ajpheart.00564.2020

    Web of Science

    PubMed

  2. Therapeutic angiogenesis using autologous adipose-derived regenerative cells in patients with critical limb ischaemia in Japan: a clinical pilot study. Reviewed

    Katagiri T, Kondo K, Shibata R, Hayashida R, Shintani S, Yamaguchi S, Shimizu Y, Unno K, Kikuchi R, Kodama A, Takanari K, Kamei Y, Komori K, Murohara T

    SCIENTIFIC REPORTS   Vol. 29 ( 10(1) ) page: 16045   2020.9

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    Language:English   Publishing type:Research paper (scientific journal)  

  3. Rationale and Design of Therapeutic Angiogenesis by Cell Transplantation Using Adipose-Derived Regenerative Cells in Patients With Critical Limb Ischemia ― TACT-ADRC Multicenter Trial ― Reviewed

    Yuuki Shimizu, Kazuhisa Kondo, Yoshihiro Fukumoto, Masayuki Takamura, Teruo Inoue, Tokuichiro Nagata, Yoshihiro J. Akashi, Yoshihiro Yamada, Koichiro Kuwahara, Yoshio Kobayashi, Rei Shibata, Toyoaki Murohara

    CIRCULATION REPORTS   Vol. 2 ( 9 ) page: 531 - 535   2020.9

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    Authorship:Lead author, Corresponding author   Publishing type:Research paper (scientific journal)   Publisher:Japanese Circulation Society  

    DOI: 10.1253/circrep.cr-20-0055

  4. Role of DJ-1 in Modulating Glycative Stress in Heart Failure Reviewed

    Shimizu Y, Nicholson CK, Polavarapu R, Pantner Y, Husain A, Naqvi N, Chin LS, Li L, Calvert JW.

    JOURNAL OF THE AMERICAN HEART ASSOCIATION   Vol. 9 ( e014691 )   2020.2

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  5. Protein Kinase N Promotes Stress-Induced Cardiac Dysfunction Through Phosphorylation of Myocardin-Related Transcription Factor A and Disruption of its Interaction with Actin. Reviewed

    Sakaguchi T, Takefuji M, Wettschureck N, Hamaguchi T, Amano M, Kato K, Tsuda T, Eguchi S, Ishihama S, Mori Y, Yura Y, Yoshida T, Unno K, Okumura T, Ishii H, Shimizu Y, Bando YK, Ohashi K, Ouchi N, Enomoto A, Offermanns S, Kaibuchi K, Murohara T.

    CIRCULATION   Vol. 140 ( 21 ) page: 1737 - 1752.   2019.11

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    Language:English   Publishing type:Research paper (scientific journal)  

  6. Cardiomyocytes capture stem cell-derived, anti-apoptotic microRNA-214 via clathrin-mediated endocytosis in acute myocardial infarction. Reviewed

    Eguchi S, Takefuji M, Sakaguchi T, Ishihama S, Mori Y, Tsuda T, Takikawa T, Yoshida T, Ohashi K, Shimizu Y, Hayashida R, Kondo K, Bando YK, Ouchi N, Murohara T.

    JOURNAL OF BIOLOGICAL CHEMISTRY   Vol. 294 ( 31 ) page: 11665 - 11674   2019.8

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    Language:English   Publishing type:Research paper (scientific journal)  

  7. Impact of Lymphangiogenesis on Cardiac Remodeling Following Ischemia and Reperfusion Injury. Reviewed

    Shimizu Y, Polavarapu R, Eskla KL, Pantner Y, Nicholson CK, Ishii M, Brunnhoelzl D, Mauria R, Husain A, Naqvi N, Murohara T, Calvert JW.

    JOURNAL OF THE AMERICAN HEART ASSOCIATION   Vol. 7 ( 19 ) page: e009565   2018.10

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

  8. Hydrogen sulfide regulates cardiac mitochondrial biogenesis via the activation of AMPK. Reviewed

    Shimizu Y, Polavarapu R, Eskla KL, Nicholson CK, Koczor CA, Wang R, Lewis W, Shiva S, Lefer DJ, Calvert JW.

    JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY   Vol. 116   page: 29-40   2018.3

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.yjmcc.2018.01.011.

  9. Diallyl Trisulfide Augments Ischemia-Induced Angiogenesis via an Endothelial Nitric Oxide Synthase-Dependent Mechanism Reviewed

    Ryo Hayashida, Kazuhisa Kondo, Sumio Morita, Kazumasa Unno, Satoshi Shintani, Yuuki Shimizu, John W. Calvert, Rei Shibata, Toyoaki Murohara

    CIRCULATION JOURNAL   Vol. 81 ( 6 ) page: 870 - 878   2017.6

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:JAPANESE CIRCULATION SOC  

    Background: Hydrogen sulfide (H2S) exerts beneficial actions against the development of cardiovascular disease. Diallyl trisulfide (DATS) is an organic polysulfide found in garlic oil that liberates H2S under physiological conditions. This study investigated whether DATS modulates endothelial cell function, as well as revascularization processes in a mouse model of hind-limb ischemia.
    Methods and Results: Wild-type (WT), endothelial nitric oxide synthase-deficient (eNOS-KO) and Akt1-heterogenic deficient (Akt-Het) mice were subjected to unilateral hindlimb ischemia (HLI). DATS or a vehicle control was injected into the abdomen of mice for up to 10 days following HLI induction. Treatment with DATS enhanced blood flow recovery and capillary density in the ischemic limbs of WT mice. This was accompanied by a reduction in apoptotic activity and oxidative stress in the ischemic muscles. DATS also increased the phosphorylation of Akt and eNOS in ischemic muscles. In contrast to WT mice, DATS did not improve blood flow of eNOS-KO and Akt-Het mice. In cultured human umbilical vein endothelium cells, DATS decreased apoptotic activity and oxidative stress under hypoxic conditions, and stimulated the phosphorylation of Akt and eNOS. Inhibition of Akt or NOS signaling reversed DATS-stimulated eNOS phosphorylation and blocked the effects of DATS on apoptosis and oxidative stress.
    Conclusions: These observations suggest that DATS promotes revascularization in response to HLI through its ability to stimulate the Akt-eNOS signaling pathway.

    DOI: 10.1253/circj.CJ-16-1097

    Web of Science

    PubMed

  10. Exercise training provides cardioprotection by activating and coupling endothelial nitric oxide synthase via a β3-adrenergic receptor-AMP-activated protein kinase signaling pathway. Reviewed

    Barr LA, Lambert JP, Shimizu Y, Barouch LA, Naqvi N, Calvert JW.

    MEDICAL GAS RESEARCH   Vol. 7 ( 1 ) page: 1-8   2017.5

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    Language:English   Publishing type:Research paper (scientific journal)  

  11. Re-Cycling KATP Channels for Cardioprotection Invited Reviewed

    Shimizu Y, Calvert JW.

    AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY   Vol. 310 ( 11 ) page: H1381-2   2016.6

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    Authorship:Lead author   Language:English  

    DOI: 10.1152/ajpheart.00309.2016.

  12. DJ-1 protects the heart against ischemia-reperfusion injury by regulating mitochondrial fission Reviewed

    Shimizu Y, Lambert JP, Nicholson CK, Kim JJ, Wolfson DW, Cho HC, Husain A, Naqvi N, Chin LS, Li L, Calvert JW.

    JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY   Vol. 97   page: 56-66   2016.4

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1016/j.yjmcc.2016.04.008.

  13. Sodium Sulfide Attenuates Ischemic-Induced Heart Failure by Enhancing Proteasomal Function in an Nrf2-Dependent Manner. Reviewed

    Shimizu Y, Nicholson CK, Lambert JP, Barr LA, Kuek N, Herszenhaut D, Tan L, Murohara T, Hansen JM, Husain A, Naqvi N, Calvert JW.

    CIRCULATION HEART FAILURE     2016.4

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1161/CIRCHEARTFAILURE.115.002368.

  14. Adipose-Derived Regenerative Cells for Cardiovascular Regeneration - A Novel Therapy for the Cardiac Conduction System. Invited Reviewed

    Shimizu Y, Calvert JW, Murohara T.

    CIRCULATION JOURNAL   Vol. 79 ( 12 ) page: 2555-6   2015.11

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    Authorship:Lead author, Corresponding author   Language:English  

    DOI: 10.1253/circj.CJ-15-1106.

  15. Hydrogen sulfide attenuates high fat diet-induced cardiac dysfunction via the suppression of endoplasmic reticulum stress Reviewed

      Vol. 46   page: 145 - 156   2015.4

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    Language:English   Publishing type:Research paper (scientific journal)  

  16. Cardiac Myocyte-Derived Follistatin-Like 1 Prevents Renal Injury in a Subtotal Nephrectomy Model Reviewed

    Satoko Hayakawa, Koji Ohashi, Rei Shibata, Yoshiyuki Kataoka, Megumi Miyabe, Takashi Enomoto, Yusuke Joki, Yuuki Shimizu, Takahiro Kambara, Yusuke Uemura, Daisuke Yuasa, Hayato Ogawa, Kazuhiro Matsuo, Mizuho Hiramatsu-Ito, Maurice J. B. van den Hoff, Kenneth Walsh, Toyoaki Murohara, Noriyuki Ouchi

      Vol. 26 ( 3 ) page: 636 - 646   2015.3

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    Language:English  

  17. Therapeutic angiogenesis by autologous adipose-derived regenerative cells: comparison with bone marrow mononuclear cells Reviewed

    Changning Hao, Satoshi Shintani, Yuuki Shimizu, Kazuhisa Kondo, Masakazu Ishii, Hongxian Wu, Toyoaki Murohara

      Vol. 307 ( 6 ) page: 869 - 879   2014.9

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    Language:English  

  18. Vildagliptin Stimulates Endothelial Cell Network Formation and Ischemia-induced Revascularization via an Endothelial Nitric-oxide Synthase-dependent Mechanism Reviewed

    Masakazu Ishii, Rei Shibata, Kazuhisa Kondo, Takahiro Kambara, Yuuki Shimizu, Tohru Tanigawa, Yasuko K. Bando, Masahiro Nishimura, Noriyuki Ouchi, Toyoaki Murohara

    JOURNAL OF BIOLOGICAL CHEMISTRY   Vol. 289 ( 39 ) page: 27235 - 27245   2014.9

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    Language:English  

  19. Multilayered adipose-derived regenerative cell sheets created by a novel magnetite tissue engineering method for myocardial infarction Reviewed

    Masakazu Ishii, Rei Shibata, Yuuki Shimizu, Takashi Yamamoto, Kazuhisa Kondo, Yoko Inoue, Noriyuki Ouchi, Tohru Tanigawa, Noriyoshi Kanemura, Akira Ito, Hiroyuki Honda, Toyoaki Murohara

    INTERNATIONAL JOURNAL OF CARDIOLOGY   Vol. 175 ( 3 ) page: 545 - 553   2014.8

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    Language:English  

  20. Neuron-derived Neurotrophic Factor Functions as a Novel Modulator That Enhances Endothelial Cell Function and Revascularization Processes Reviewed

    Koji Ohashi, Takashi Enomoto, Yusuke Joki, Rei Shibata, Yasuhiro Ogura, Yoshiyuki Kataoka, Yuuki Shimizu, Takahiro Kambara, Yusuke Uemura, Daisuke Yuasa, Kazuhiro Matsuo, Satoko Hayakawa, Mizuho Hiramatsu-Ito, Toyoaki Murohara, Noriyuki Ouchi

    JOURNAL OF BIOLOGICAL CHEMISTRY   Vol. 289 ( 20 ) page: 14132 - 14144   2014.5

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  21. Analogy of entrainment (respiratory modulation) of heartbeats in cheyne-stokes respiration in heart failure and respiratory sinus arrhythmia: Its physiological significance Reviewed

    Fumihiko Yasuma, Tamotsu Tanahashi, Jun Ichiro Hayano, Yuuki Shimizu, Toyoaki Murohara

    Respiration and Circulation   Vol. 61   page: 944 - 950   2013.10

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    Language:English  

  22. Adiponectin-Mediated Modulation of Lymphatic Vessel Formation and Lymphedema Reviewed

    Yuuki Shimizu, Rei Shibata, Masakazu Ishii, Koji Ohashi, Takahiro Kambara, Yusuke Uemura, Daisuke Yuasa, Yoshiyuki Kataoka, Shinji Kihara, Toyoaki Murohara, Noriyuki Ouchi

    JOURNAL OF THE AMERICAN HEART ASSOCIATION   Vol. 2 ( 5 ) page: e000438   2013.10

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    Authorship:Lead author   Language:English  

  23. Preoperative Management of Deteriorating Mitral Regurgitation and Heart Failure with Continuous Positive Airway Pressure Reviewed

    Fumihiko Yasuma, Tamotsu Tanahashi, Toshimitsu Mori, Yuuki Shimizu, Toyoaki Murohara

    INTERNAL MEDICINE   Vol. 52 ( 15 ) page: 1709 - 1713   2013

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    Language:English  

  24. Therapeutic Impact of Follistatin-Like 1 on Myocardial Ischemic Injury in Preclinical Models Reviewed

    Yasuhiro Ogura, Noriyuki Ouchi, Koji Ohashi, Rei Shibata, Yoshiyuki Kataoka, Takahiro Kambara, Tetsutaro Kito, Sonomi Maruyama, Daisuke Yuasa, Kazuhiro Matsuo, Takashi Enomoto, Yusuke Uemura, Megumi Miyabe, Masakazu Ishii, Takashi Yamamoto, Yuuki Shimizu, Kenneth Walsh, Toyoaki Murohara

    CIRCULATION   Vol. 126 ( 14 ) page: 1728   2012.10

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    Language:English  

  25. Therapeutic Lymphangiogenesis With Implantation of Adipose-Derived Regenerative Cells Reviewed

    Yuuki Shimizu, Rei Shibata, Satoshi Shintani, Masakazu Ishii, Toyoaki Murohara

    JOURNAL OF THE AMERICAN HEART ASSOCIATION   Vol. 1 ( 4 ) page: e000877   2012.8

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    Authorship:Lead author   Language:English  

  26. CTRP9 Protein Protects against Myocardial Injury following Ischemia-Reperfusion through AMP-activated Protein Kinase (AMPK)-dependent Mechanism Reviewed

    Takahiro Kambara, Koji Ohashi, Rei Shibata, Yasuhiro Ogura, Sonomi Maruyama, Takashi Enomoto, Yusuke Uemura, Yuuki Shimizu, Daisuke Yuasa, Kazuhiro Matsuo, Megumi Miyabe, Yoshiyuki Kataoka, Toyoaki Murohara, Noriyuki Ouchi

    JOURNAL OF BIOLOGICAL CHEMISTRY   Vol. 287 ( 23 ) page: 18965 - 18973   2012.6

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  27. Optical Coherence Tomography Images of a Coronary Artery Aneurysm in an Infarct-Related Artery 6 Months After Bare-Metal Stent Implantation Reviewed

    Daiji Yoshikawa, Hideki Ishii, Yutaka Aoyama, Hitoshi Ichimiya, Yuuki Shimizu, Satoshi Isobe, Satoshi Shintani, Yasuko Kureishi-Bando, Toyoaki Murohara

    JACC-CARDIOVASCULAR INTERVENTIONS   Vol. 3 ( 12 ) page: 1300 - 1302   2010.12

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  28. Evidence for the Therapeutic Potential of Ex Vivo Expanded Human Endothelial Progenitor Cells Using Autologous Serum Reviewed

    Takanori Shumiya, Rei Shibata, Yuuki Shimizu, Masakazu Ishii, Ryuji Kubota, Satoshi Shintani, Toyoaki Murohara

    CIRCULATION JOURNAL   Vol. 74 ( 5 ) page: 1006 - 1013   2010.5

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    Language:English  

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Books 13

  1. 疾患モデルの作成と利用―循環器疾患

    清水優樹 都築一仁 室原豊明( Role: Joint author ,  下肢虚血モデル)

    エル・アイ・シー出版社  2021.3 

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    Language:English

  2. 透析患者PADの最前線

    都築一仁, 清水優樹, 柴田玲, 室原豊明( Role: Contributor ,  再生医療(2)脂肪組織由来間葉系前駆細胞移植)

    臨床透析  2020.7 

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    Language:English

  3. Journal of Clinical and Experimental Medicine

    Yuuki Shimizu( Role: Contributor ,  Therapeutic angiogenesis by adipose-derived regenerative cells)

    2019.2 

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    Language:English

  4. 体性幹細胞を用いた血管新生療法

    近藤和久, 林田竜, 清水優樹, 柴田玲, 室原豊明( Role: Contributor)

    メディカルレビュー社  2017 

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    Language:English

  5. 血管新生研究の最先端 血管再生療法

    清水優樹, 室原豊明( Role: Contributor ,  細胞治療)

    医薬ジャーナル社  2013 

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    Language:Japanese

  6. 特集:末梢動脈疾患(PAD)~増加する動脈硬化性疾患、適切な診断と治療法~

    清水優樹, 室原豊明( Role: Contributor ,  末梢動脈疾患における血管再生療法)

    南江堂  2013 

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    Language:Japanese

  7. 入門 血管新生学

    清水優樹, 室原豊明(血管再生療法)

    メディカルレビュー社  2013 

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    Language:Japanese

  8. 増刊号『脂質異常症』 -基礎・臨床研究の最新知見-

    清水優樹, 室原豊明( Role: Contributor ,  再生治療の現状と課題)

    日本臨床社  2013 

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    Language:Japanese

  9. 血管・心筋再生はどこまできたか

    柴田玲, 清水優樹, 室原豊明( Role: Contributor)

    メディカルレビュー  2011 

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    Language:Japanese

  10. 重症虚血肢の診断と血管再生療法の適応について考える

    柴田玲, 清水優樹, 室原豊明( Role: Contributor)

    メジカルビュー社  2011 

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    Language:Japanese

  11. 動脈硬化の再生医療の現状と展望

    清水優樹, 新谷 理, 泉 雄介, 小椋康弘, 室原豊明( Role: Contributor)

    Parma Medica  2011 

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    Language:Japanese

  12. 細胞移植による血管再生療法と今後の課題

    室原豊明, 新谷 理, 小椋康弘, 清水優樹

    細胞工学  2010 

  13. 血管再生療法は重症虚血肢を救えるか

    室原豊明, 新谷 理, 小椋康弘, 清水優樹

    メディカルレビュー社  2010 

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    Language:Japanese

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Presentations 20

  1. シンポジウム36 「下肢血管再生治療の最前線」

    清水優樹, 柴田玲, 室原豊明

    第20回日本再生医療学会総会  2021.3.11 

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    Event date: 2021.3

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

  2. シンポジウム 心血管病における組織リンパ管の役割とその治療応用

    清水優樹

    第44回日本リンパ学会総会 シンポジウム1  2020.9.12 

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    Event date: 2020.9

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

  3. 合同シンポジウム2 虚血部血管新生におけるリンパ管新生の役割 Invited

    清水優樹

    第52回日本動脈硬化学会総会・学術集会  2020.7.18 

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    Event date: 2020.7

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

  4. シンポジウム ISHR会長特別企画 Invited

    清水 優樹

    ISHR  2019.12.14 

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    Event date: 2019.12

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

  5. シンポジウム1 血管新生機構の解明と再生医療 Invited

    清水 優樹

    JVBMO  2019.12.14 

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    Event date: 2019.12

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  6. シンポジウム 再生医学・医療 Invited

    清水 優樹

    第51回日本臨床分子形態学会総会・学術集会  2019.9.20 

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    Event date: 2019.9

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  7. シンポジウム リンパ管増生と心筋リモデリング Invited

    清水 優樹

    第5回 日本心筋症研究会  2019.7.13 

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    Event date: 2019.7

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  8. シンポジウム 再生医療の最前線 Invited

    清水 優樹

    第17回 日本フットケア学会年次学術集会  2019.2.10 

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    Event date: 2019.2

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

  9. Research promotion seminars by JCS members studying abroad Invited International conference

    Yuuki Shimizu

    2017.3.18 

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    Event date: 2017.3

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

  10. Therapeutic lymphangiogenesis ameliorates cardiac dysfunction in the setting of ischemic-induced heart failure International coauthorship International conference

    Yuuki Shimizu, Rohini Polavarapu, Toyoaki Murohara, John W. Calvert

    AHA scientific session  2016.11 

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    Event date: 2016.11

    Language:English   Presentation type:Poster presentation  

    Venue:New Orleans  

  11. Hydrogen Sulfide Promotes Mitochondrial Biogenesis Through the Regulation of AMP-activated Protein Kinase International coauthorship International conference

    Yuuki Shimizu, Rohini Polavarapu, John Calvert

    BCVS Scientific Sessions  2016.7 

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    Event date: 2016.7

    Language:English   Presentation type:Poster presentation  

    Venue:Phoenix  

  12. DJ-1 Gene Therapy Opposes the Development of Ischemic Heart Failure International coauthorship International conference

    Yuuki Shimizu: Di Sha, Lih-Shen Chin, Lian Li, John W. Calvert

    2016.7 

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    Event date: 2016.7

    Language:English   Presentation type:Poster presentation  

    Venue:Phoenix  

  13. DJ-1/Park7 Protects the Heart Against Ischemia-Reperfusion Injury through the modulation of SUMOylation International coauthorship International conference

    Yuuki Shimizu, Larry Barr, Travis Fields, John W. Calvert

    AHA scientific session  2015.11 

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    Event date: 2015.11

    Language:English   Presentation type:Poster presentation  

    Venue:Orlando  

  14. Adiponectin stimulates lymphangiogenesis and ameliorates secondary lymphedema International conference

    Yuuki Shimizu, Rei Shibata, Koji Ohashi, Masakazu Ishii, Satoshi Shintani, Toyoaki Murohara, Noriyuki Ouchi

    AHA scientific session  2012.11 

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    Event date: 2012.11

    Language:English   Presentation type:Poster presentation  

  15. Adipose-derived regenerative cells implantation alleviates lymphedema via augmentation of VEGF-C mediated M2 macrophage mobilization International conference

    Yuuki Shimizu, Satoshi Shintani, Rei Shibata, Masakazu Ishii, Hao Chang-ning, Ryo Hayashida, Toyoaki Murohara

    2012.11 

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    Event date: 2012.11

    Language:English   Presentation type:Poster presentation  

    Venue:Los Angeles  

  16. A Novel Therapeutic Strategy for Secondary Lymphedema by Adipose-Derived Regenerative Cells International conference

    Yuuki Shimizu, Satoshi Shintani, Rei Shibata, Masakazu Ishii, Hao Changning, Toyoaki Murohara

    2012.3 

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    Event date: 2012.3

    Language:Japanese  

  17. 再生医療研究の最先端 Invited

    清水優樹 新谷理 室原豊明

    第41回 日本心脈管作動物質学会  2012.2.10 

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    Event date: 2012.2

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

    Venue:秋田  

  18. Implantation of adipose-derived regenerative cells enhances lymphangiogenesis and improves secondary lymphedema International conference

    Yuuki Shimizu, Satoshi Shintani, Rei Shibata, Yusuke Izumi, Yasuhiro Ogura, Masakazu Ishii, Toyoaki Murohara

    AHA scientific session  2011.11 

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    Event date: 2011.11

    Language:English   Presentation type:Poster presentation  

  19. M2 macrophages contribute to postnatal lymphangiogenesis as lymphatic endothelial cell progenitors. International conference

    Yuuki Shimizu, Satoshi Shintani, Rei Shibata, Yusuke Izumi, Yasuhiro Ogura, Masakazu Ishii, Toyoaki Murohara

    2011.11 

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    Event date: 2011.11

    Language:English   Presentation type:Oral presentation (general)  

    Venue:Orlando  

  20. Therapeutic lymphangiogenesis with implantation of adipose-derived regenerative cells International conference

    Yuuki Shimizu, Satoshi Shintani, Rei Shibata, Yusuke Izumi, Yasuhiro Ogura, Masakazu Ishii, Toyoaki Murohara

    2011.8 

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    Event date: 2011.8

    Language:English   Presentation type:Poster presentation  

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Other research activities 3

  1. 日本血管生物医学会 評議員

    2020.4

  2. 国際心臓研究学会 (ISHR) 日本部会 若手活性化プロジェクトメンバー(U45SWG)

    2019.3

  3. ヒト皮下脂肪由来間葉系前駆細胞を用いた重症虚血肢に対する血管新生療法

    2015.11

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    全国8施設共同臨床研究(jRCTb040190118) 統轄機関

KAKENHI (Grants-in-Aid for Scientific Research) 2

  1. 難治性心臓病を標的とした新規リンパ管新生療法の開発研究

    Grant number:19K17519  2019.4 - 2022.3

    若手研究

    清水 優樹

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

    課題1として、心臓リンパ管の生理学的状況下および心不全発症過程での役割の解明に取り組む。まずは、生理学的条件下の心臓におけるリンパ管の機能解析を行ったのちに、心筋炎後心不全発症過程において誘導される内因性リンパ管新生の観察と、その機能解析を機能阻害実験などにより検討する。最後に、心不全に対する治療的リンパ管新生の開発を予定する。
    課題2として、虚血耐性現象における新規心保護機序としての心臓リンパ管の役割の解明に取り組む。まずは虚血耐性現象により誘導されるリンパ管再構築の検討および、虚血耐性現象によるリンパ管再構築機序の検討をする。さらに、リンパ管新生調節によるIPC調節効果を検証する。
    (課題1)心臓リンパ管の生理学的状況下および心不全発症過程での役割の解明
    生理学的条件下の心臓におけるリンパ管の機能解析に取り組んだ。野生型マウス(雄; 10~12週齢)を麻酔下に開胸して、心尖部にエバンスブルーを注入して左室心筋より同色素がドレナージされる過程で、リンパ管の走行を検出・同定し心臓から集約される集合リンパ管を結紮することにより心臓のリンパ管系システム機能不全を誘導した。心臓リンパ管系機能不全に陥った際の心臓構造および機能における変化(結紮前、結紮後7日目、14日目、28日目、56日目)を経時的に観察し、線維化評価(Masson Trichrome染色)を行った。また、その際の心臓リンパ管の形態的・数的変化を評価する目的で免疫染色(LYVE1およびPodoplaninでリンパ管を同定)をそれぞれ施行した。心臓リンパ管機能不全は、左室心外膜側のリンパ管の拡張変化を伴い、また、一部は繊維化形成所見が認められた。
    <BR>
    (課題2)虚血耐性現象により誘導されるリンパ管再構築の検討
    マウスLangendorff灌流モデルを用いてEx vivoでの検証を行った。 Ischemic preconditioning (IPC)作成protocolは、既存の報告にしたがって、5分間の灌流停止と5分間の再灌流を3回繰り返し行う。引き続いて45分の灌流停止と15分の再灌流を行い、虚血再灌流(I/R)モデルの作成に取り掛かった。現在引き続き安定した同モデル確立を目指している段階である。
    課題2に関して、モデル確立が手技的に予想以上に困難であり、その後の実験が遅れている。本プロジェクト全体として、現時点では、まずは課題1を中心に進めて行く。
    (課題1)心臓リンパ管の生理学的状況下および心不全発症過程での役割の解明
    本年度の計画として、引き続きマウスサンプルサイズを増やして、心エコーなどによる心機能に及ぼす影響を評価する。その後、病態モデルでの評価に取り掛かる。心筋炎モデル作成後に心臓リンパ管システム機能を阻害する。さらには病態心での炎症、浮腫、心機能および心臓リンパ管の関連を免疫染色、ウエスタンブロットおよびqPCRを用いて評価する。最後に、心不全発症過程において内因性のリンパ管再生を、今度は“薬物的に”阻害(VFGFR3阻害薬、VEGF-C中和抗体投与)することにより、局所炎症および心筋浮腫に及ぼす影響を評価し、心臓リモデリングへの影響を同様に検証する。
    <BR>
    (課題2)虚血耐性現象により誘導されるリンパ管再構築の検討
    リンパ管内皮細胞(LEC)を用いたvitro実験で検証を行う。細胞膜表面の受容体などはendocytosisおよびexocytosisによっても密度が調節されており、最近の報告からはIPCもこのメカニズムにて細胞膜表面上のKATP Channelをリサイクルしていることが示唆されている。そこで、今回はIPCがリンパ管新生を促進する一つの機序として「リンパ管内皮細胞(LEC)細胞膜表面上のVEGFR3密度を、IPCのendocytosisおよびexocytosisの機序により調整し、リンパ管形成能が調節されるか否か」を検証する。

  2. Translational research of lymphangiogenesis for cardiovascular diseases

    Grant number:17H06745  2017.8 - 2019.3

    Shimizu Yuuki

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    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\2730000 ( Direct Cost: \2100000 、 Indirect Cost:\630000 )

    Lymphedema is one of the serious clinical problems which can occur after surgical resection of malignant tumors such as breast cancer or intra-pelvic cancers. However, no effective treatment options exist at present. Diallyl trisulfide (DATS) is an organic polysulfide found in garlic oil and able to release H2S through interactions with biological thiols, including glutathione. So, DATS can act as a H2S donor. Previously we reported that DATS can promote angiogenesis in hind limb ischemia. However, it is currently unknown whether H2S can augment lymphangiogenesis and improve lymphedema.
    In a present project, our data documented that DATS functions as a novel regulator of lymphatic-vascular responses to lymphedema and importantly, therapeutic approaches aimed at augmenting exogenous H2S using H2S-releasing agents could be potentially useful for treating secondary lymphedema.

 

Teaching Experience (On-campus) 4

  1. 臨床実習2

    2020

  2. JMECC

    2020

  3. 臨床実習1

    2020

  4. チュートリアル

    2017

 

Social Contribution 2

  1. 日本内科学会救急ICLS講習会(JMECC)インストラクター

    Role(s):Lecturer

    2019.11

  2. ICLSインストラクター

    Role(s):Lecturer

    2019.11

Media Coverage 1

  1. 幹細胞でリンパ管再生 ーリンパ浮腫治療へ道筋ー Newspaper, magazine

    中日新聞朝刊   3面  2012.7

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    Author:Myself 

Academic Activities 1

  1. 厚生労働省難治性血管炎に関する調査研究 大型血管炎臨床分科会協力者

    Role(s):Planning/Implementing academic research

    2020.8

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    Type:Academic research