Toshio Miyata, MD, PhD
Brief History
In 1986, Graduated Nagoya University School of Medicine,
Up to November 2007, Professor, Department of Nephrology and Metabolism and Director, Institute of Medical Sciences at Tokai University School of Medicine, following Assistant Professor at Research Institute for Microbial Diseases, Osaka University and Associate Professor, Department of Internal Medicine at Nagoya University School of Medicine,
Current position
Professor and Special Assistant to the Dean (Research and Industry-University Collaboration), Tohoku University Graduate School of Medicine
・Permanent Member, the Royal Academy of Belgium
・Program Supervisor, " Science and Technology Platform Program for Advanced Biological Medicine", Japan Agency for Medical Research and Development
・Member of the Council for Drug Development, Headquarters for Healthcare Policy , Cabinet Secretariat
・Member of Life Science Committee, Ministry of Education, Culture, Sports, Science and Technology
・Hiroshima University Hiroshima Clinical Research and Development Promotion Center Visiting Professor
・Tokai University Visiting Professor
・Member of Public-Private Dialogue for the Creation of Innovative Drugs and Medical Devices, Ministry of Health, Labour and Welfare
Publications
| Ibrahim A.A, Fujimura T, Uno T, Terada T, Hirano K.-I, Hosokawa H, Ohta A, Miyata T, Ando K, Yahata T. Plasminogen activator inhibitor-1 promotes immune evasion in tumors by facilitating the expression of programmed cell death-ligand 1. Frontiers in Immunology. 2024; 15. |  download |
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| Masuda T, Hirata T, Sakamoto T, Tsubata Y, Ichihara E, Kozuki T, Shoda H, Motonaga M, Yoshida T, Fukutani M, Tsuji-Takayama K, Tamura A, Amagase H, Fujihara H, Aoki G, Akita T, Orihashi Y, Miyata T, Hattori N. Treatment rationale and protocol design: an investigator-initiated phase II study of. Journal of Thoracic Disease. 2024;16: 3381-3388. | download |
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| Hirai T, Asano K, Ito I, Miyazaki Y, Sugiura H, Agirbasli M, Kobayashi S, Kobayashi M, Shimada D, Natsume I, Kawasaki T, Ohba T, Tajiri S, Sakamaki F, Mineshita M, Takihara T, Sekiya K, Tomii K, Tomioka H, Kita H, Nishizaka Y, Fukui M, Miyata T, Harigae H. A randomized double-blind placebo-controlled trial of an inhibitor of plasminogen activator inhibitor-1 (TM5614) in mild to moderate COVID-19. Scientific Reports. 2024; 14:165. | download |
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| Fujimura T, Yoshino K, Nakamura M, Kato H, Ito T, Maekawa T, Fujisawa Y, Matsushita S, Amagai R, Yamazaki E, Takahashi M, Tamabuchi E, Hashimoto A, Kambayashi Y, Yamazaki N, Miyata T, Asano Y. Efficacy and safety of TM5614 in combination with paclitaxel in the treatment of paclitaxel-resistant cutaneous angiosarcoma: Phase II study protocol. Experimental Dermatology. 2024; 33. | download |
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| Takahashi N, Kameoka Y, Onizuka M, Onishi Y, Takahashi F, Miyata T, Ando K, Harigae H. Deep molecular response in patients with chronic phase chronic myeloid leukemia treated with the plasminogen activator inhibitor-1 inhibitor TM5614 combined with a tyrosine kinase inhibitor. Cancer Medicine. 2023; 12: 4250-4258 | download |
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| Sonoda K, Bogahawaththa S, Katayama A, Ujike S, Kuroki S, Kitagawa N, Hirotsuru K, Suzuki N, Miyata T, Kawaguchi S, Tsujita T. Prolyl Hydroxylase Domain Protein Inhibitor Not Harboring a 2-Oxoglutarate Scaffold Protects against Hypoxic Stres ACS Pharmacology and Translational Science. 2022; 5: 512. | download |
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| Hirai S , Miwa H , Tanaka T , Toriumi K , Kunii Y , Shimbo H , Sakamoto T , Hino M ,IzumiR, Nagaoka A , Yabe Y , Nakamachi T , Shioda S , Dan T , Miyata T, Nishito Y , Suzuki K , Miyashita M , Tomoda T , Hikida T, Horiuchi J ,Itokawa M , Arai M , Okado H. High-sucrose diets contribute to brain angiopathy with impaired glucose uptake and psychosis-related higher brain dysfunctions in mice. Science Advances 2021; 12: 7. | download |
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| Toriumi K, Berto S, Koike K, Usui K, Dan T, Suzuki K, Miyashita M, Horiuchi Y, Yoshikawa A, Sugaya Y, Watanabe T, Asakura M, Kano M, Ogasawara Y, Miyata T , Itokawa M, Konopka G ,Arai M. Combined glyoxalase 1 dysfunction and vitamin B6 deficiency in a schizophrenia model system causes mitochondrial dysfunction in the prefrontal cortex. Redox Biol. 2021; 45: 102057. | download |
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| Koike S, Toriumi K, Kasahara S, Kibune Y, Ishida Y, Takashi D, Miyata T, Arai M,OgasawaraY. Accumulation of carbonyl proteins in the brain of mouse model for methylglyoxaldetoxification deficits. Antioxidants. 2021; 10: 574. | download |
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| Ghosh AK, Soberanes S, Lux E, Shang M, Aillon RP, Eren M, Budinger GRS, Miyata T, Vaughan DE. Pharmacological inhibition of PAI-1 alleviates cardiopulmonary pathologies induced by exposure to air pollutants PM2.5. Environ Pollut. 2021; 287: 117283: | download |
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| Sillen M, Miyata T, Vaughan DE, Strelkov SV and Declerck PJ. Structural insight into the two-step mechanism of PAI-1 inhibition by small molecule TM5484. Int J Mol Sci. 2021; 22: 1482. | download |
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| Levine J A, Oleaga C, Mesut E, Amaral Ansel P, Shang S, Lux E, Khan S , Shah S J, Omura Y, Pamir N, Hay J, Barish G, Miyata T, Tavori H, Fazio S and Vaughan D E. role of PAI‑1 in hepatic steatosis and dyslipidemia. Scientific Reports. 2021; 11: 430. | download |
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| Nakayama M, Hamada C, Yokoyama K, Tanno Y, Matsuo N, Nakata J, Ishibashi Y, Okuzawa A, Sakamoto K, Nara T, Kakuta T, Nangaku M, Yokoo T, Suzuki Y, Miyata T. A disposable, ultra fine endoscope for non invasive, close examination of the intraluminal surface of the peritoneal dialysis catheter and peritoneal cavity. Scientific Reports. 2020; 10: 17565. | download |
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| Rana T, Jiang C, Liu G, Miyata T, Antony V, Thannickal VJ, Liu RM. PAI-1 regulation of TGF-β1-induced alveolar type II cell senescence, SASP secretion,and SASP-mediated activation of alveolar macrophages. Am J Respir Cell Mol Biol. 2020; 62: 319-330. | download |
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| Yahata T, Ibrahim AA, Hirano KI, Muguruma Y, Naka K, Hozumi K, Vaughan DE, Miyata T, Ando K. Targeting of plasminogen activator inhibitor-1 activity promotes elimination of chronic myeloid leukemia stem cells. Haematologica. 2020; 30: 230227. | download |
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| Sun T, Ghosh AK, Eren M, Miyata T, Vaughan DE. PAI-1 contributes to homocysteine-induced cellular senescence. Cell Signal. 2019; 64: 109394. | download |
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| Akhter H, Huang WT, van Groen T, Kuo HC, Miyata T, Liu RM. A small molecule inhibitor of plasminogen activator inhibitor-1 reduces brain Amyloid-β load and improves memory in an animal model of alzheimer's disease. J Alzheimers Dis. 2018; 64: 447-457. | download |
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| Lee S.M.; Dorotea D.; Jung I.; Nakabayashi T.; Miyata T.; Ha H. TM5441, a plasminogen activator inhibitor-1 inhibitor, protects against high fat diet-induced non-alcoholic fatty liver disease. Oncotarget.2017;8:89746-89760. | download |
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| Khan SS, Shah S J, Klyachko E, Baldridge AS, Eren M, Place A T, Aviv A, Puterman E, Lloyd-Jones DM, Heiman M, Miyata T, Gupta S, Shapiro AD, Vaughan DE. A null mutation in SERPINE1 protects against biological aging in humans. Science Advances 2017; 3: 1617. | download |
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| Yahata T, Ibrahim A, Muguruma Y, Eren M, Shaffer AM, Watanabe N, Kaneko S, Nakabayashi N, Dan T, Hirayama N, Vaughan DE, Miyata T, Ando K. Tgf-β-induced intracellular PAI-1 is responsible for retaining hematopoietic stem cells in the niche. Blood. 2017; 130: 2283-2294. | download |
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| Eren M, Place AT, Thomas PM, Flevaris P, Miyata T, Vaughan DE. PAI-1 is a critical regulator of FGF23 homeostasis. Science Advances. 2017; 3: e1603259. | download |
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| Honjo T, Munakata S, Tashiro Y, Salama Y, Shimazu H, Eiamboonsert S, Dhahri D, Ichimura A, Dan T, Miyata T, Takeda K, Sakamoto K, Hattori K, Heissig B. Plasminogen activator inhibitor-1 regulates macrophage-dependent postoperative adhesion by enhancing EGF-HER1 signaling in mice. FASEB J. 2017; 31: 2625-2637. | download |
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| Ghosh AK, Rai R, Park KE, Eren M, Miyata T, Wilsbacher LD, Vaughan DE. A small molecule inhibitor of PAI-1 protects against Doxorubicin-induced cellular senescence: molecular basis. Oncotarget. 2016; 45: 72443-72457. | download |
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| Jeong BY, Uddin MJ, Park JH, Lee JH, Lee HB, Miyata T, Ha H. Novel plasminogen activator inhibitor-1 inhibitors prevent diabetic kidney injury in a mouse model. PLoS One. 2016; 11: e0157012. | download |
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| Liu RM, Eldridge S, Watanabe N, Deshane J, Kuo HC, Jiang C, Wang Y, Liu G, Schwiebert L, Miyata T, Thannickal VJ. Therapeutic potential of an orally effective small molecule inhibitor of plasminogen activator inhibitor for asthma. Am J Physiol Lung Cell Mol Physiol. 2016; 15: 328-336. | download |
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| Maessen DE, Brouwers O, Gaens KH, Wouters K, Cleutjens JP, Janssen BJ, Miyata T, Stehouwer CD, Schalkwijk CG. Delayed intervention with pyridoxamine improves metabolic function and prevents adipose tissue inflammation and insulin resistance in high-fat diet-induced obese mice. Diabetes. 2016; 65: 956-966. | download |
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| Piao L, Jung I, Huh JY, Miyata T, Ha H. A novel plasminogen activator inhibitor-1 inhibitor, TM5441, protects against high-fat diet-induced obesity and adipocyte injury in mice. British J Pharmacology. 2016; 173: 2622-2632. | download |
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| Souma T, Nezu M, Nakano D, Yamazaki S, Hirano I, Sekine H, Dan T, Takeda K, Fong GH, Nishiyama A, Ito S, Miyata T, Yamamoto M, Suzuki N. Erythropoietin synthesis in renal myofibroblasts is restored by activation of hypoxia signaling. J Am Soc Nephrol. 2016; 27: 428-438. | download |
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| Tojo Y, Sekine H, Hirano I, Pan X, Souma T, Tsujita T, Kawaguchi SI, Takeda N, Takeda K, Fong GH, Dan T, Ichinose M, Miyata T, Yamamoto M, Suzuki N. Hypoxia signaling cascade for erythropoietin production in hepatocytes. Mol Cell Biol. 2015; 15 : 2658-2672. | download |
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| Pelisch N, Dan T, Ichimura A, Sekiguchi H, Vaughan DE, van Ypersele de Strihou C, Miyata T. Plasminogen Activator Inhibitor-1 Antagonist TM5484 Attenuates Demyelination and Axonal Degeneration in a Mice Model of Multiple Sclerosis. PLoS One. 2015; 10: e0124510. | download |
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| Boe AE, Eren M, Morales-Nebreda L, Murphy SB, Budinger GR, Mutlu GM, Miyata T, Vaughan DE. Nitric oxide prevents alveolar senescence and emphysema in a mouse model. PLoS One. 2015; 10: e0116504. | download |
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| Placencio VR, Ichimura A, Miyata T, DeClerck YA. Small Molecule Inhibitors of Plasminogen Activator Inhibitor-1 Elicit Anti-Tumorigenic and Anti-Angiogenic Activity. PLoS One. 2015; 10: e0133786. | download |
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| Kobayashi N, Ueno T, Ohashi K, Yamashita H, Takahashi Y, Sakamoto K, Manabe S, Hara S, Takashima Y, Dan T, Pastan I, Miyata T, Kurihara H, Matsusaka T, Reiser J, Nagata M. Podocyte injury-driven intracapillary plasminogen activator inhibitor type 1 accelerates podocyte loss via beta 1 integrin endocytosis. Am J Physiol Renal Physiol. 2015; 308: F614-26. | download |
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| Miyashita M.; Arai M.; Yuzawa H.; Niizato K.; Oshima K.; Kushima I.; Hashimoto R.; Fukumoto M.; Koike S.; Toyota T.; Ujike H.; Arinami T.; Kasai K.; Takeda M.; Ozaki N.; Okazaki Y.; Yoshikawa T.; Amano N.; Miyata T.; Itokawa M. Replication of enhanced carbonyl stress in a subpopulation of schizophrenia. Psychiatry and Clinical Neurosciences.2014;68:83-84. | download |
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| Eren M, Boe A, Murphy SB, Place AT, Nagpal V, Morales-Nebreda L, Urich D, Quaggin SE, Budinger GS, Mutlu GM, Miyata T, Vaughan DE. PAI-1-regulated extracellular proteolysis governs senescence and survival in Klotho mice. Proc Natl Acad Sci USA. 2014; 111: 7090-7095. | download |
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| Miyata T, Ando T, Hiragi H,Watanabe K, Yamamoto F, Vaughan D.E, Prof. van Ypersele de Strihou C, Takeuchi M. Drug discovery in renal disease--towards a more efficient framework. Nature Review Nephrology. 2014; 10: 290-296. | download |
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| Jo-Watanabe A, Ohse T, Nishimatsu H, Takahashi M, Ikeda Y, Wada T, Shirakawa JI, Nagai R, Miyata T, Nagano T, Hirata Y, Inagi R, Nangaku M. Glyoxalase I reduces glycative and oxidative stress and prevents age-related endothelial dysfunction through modulation of endothelial nitric oxide synthase phosphorylation. Aging Cell. 2014; 13: 519-528. | download |
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| Brouwers O, Niessen PM, Miyata T, Østergaard JA, Flyvbjerg A, Peutz-Kootstra CJ, Sieber J, Mundel PH, Brownlee M, Janssen BJ, De Mey JG, Stehouwer CD, Schalkwijk CG. Glyoxalase-1 overexpression reduces endothelial dysfunction and attenuates early renal impairment in a rat model of diabetes. Diabetologia. 2014; 57: 224-235. | download |
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| Ibrahim AA, Yahata T, Onizuka M, Dan T, van Ypersele de Strihou C, Miyata T, Ando K. Inhibition of Plasminogen Activator Inhibitor Type-1 Activity Enhances Rapid and Sustainable Hematopoietic Regeneration. Stem Cells. 2014; 32: 946-58. | download |
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| Boe A, Eren M, Murphy S, Kamide1 C, Ichimura A, Terry D, McAnally D, Smith LH, Miyata T, Vaughan DE. Plasminogen activator inhibitor-1 antagonist TM5441 attenuates Nω-nitro-L-arginine methyl ester-induced hypertension and vascular senescence. Circulation. 2013; 128: 2318-24. | download |
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| Ichimura A, Matsumoto S, Suzuki S, Dan T, Yamaki S, Sato Y, Kiyomoto H, Ishii N, Okada K, Matsuo O, Hou FF, Vaughan DE, van Ypersele de Strihou C, Miyata T. A Small Molecule Inhibitor to Plasminogen Activator Inhibitor 1 Inhibits Macrophage Migration. Arterioscler Thromb Vasc Biol. 2013; 33: 935-942. | download |
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| Remuzzi G, Benigni A, Finkelstein FO, Grunfeld JP, Joly D, Katz I, Liu ZH, Miyata T, Perico N, Rodriguez-Iturbe B, Antiga L, Schaefer F, Schieppati A, Schrier RW, Tonelli M. Kidney failure: aims for the next 10 years and barriers to success Lancet. 2013; 382: 353-362. | download |
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| Miyata T, Suzuki N, van Ypersele de Strihou C. Diabetic nephropathy: Are there new and potentially promising therapies targeting oxygen biology? Kidney Int. 2013; 84: 693-702. | download |
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| Zhou LL, Cao W, Xie C, Tian J, Zhou Z, Zhou Q, Zhu P, Li A, Liu Y, Miyata T, Hou FF, Nie J. The receptor of advanced glycation end products plays a central role in advanced oxidation protein products-induced podocyte apoptosis. Kidney Int. 2012; 82: 759-770. | download |
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| Tashiro Y, Nishida C, Sato-Kusubata K, Ohki-Koizumi M, Ishihara M, Sato A, Gritli I, Komiyama H, Sato Y, Dan T, Miyata T, Okumura K, Tomiki Y, Sakamoto K, Nakauchi H, Heissig B, Hattori K. Inhibition of PAI-1 induces neutrophil-driven neoangiogenesis and promotes tissue regeneration via production of angiocrine factors in mice. Blood. 2012; 119: 6382-6393. | download |
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| Berner AK, Brouwers O, Pringle R, Klaassen I, Colhoun L, McVicar C, Brockbank S, Curry JW, Miyata T, Brownlee M, Schlingemann RO, Schalkwijk C, Stitt AW. Protection against methylglyoxal-derived AGEs by regulation of glyoxalse-1 prevents retinal neuroglial and vasodegenerative pathology. Diabetologia. 2012; 55: 845-854. | download |
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| Huang WT, Vayalil PK, Miyata T, Hagood J, Liu RM. Therapeutic value of small molecule inhibitor to plasminogen activator inhibitor-1 for lung fibrosis. Am J Respir Cell Mol Biol. 2012; 46: 87-95. | download |
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| K. Tanaka, Y. Tani, J. Asai, F. Nemoto, Y. Kusano, H. Suzuki, Y. Hayashi, K. Asahi, M. Nakayama, T. Miyata1 and T. Watanabe. Skin autofluorescence is associated with severity of vascular complications in Japanese patients with Type 2 diabetes. Diabet Med. 2012; 29: 492-500. | download |
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| Brouwers O.; Niessen P.M.; Ferreira I.; Miyata T.; Scheffer P.G.; Teerlink T.; Schrauwen P.; Brownlee M.; Stehouwer C.D.; Schalkwijk C.G. Overexpression of glyoxalase-I reduces hyperglycemiainduced levels of advanced glycation end products and oxidative stress in diabetic rats. J Biol Chem. 2011;286:1374-1380. | download |
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| Ikeda Y, Inagi R, Miyata T, Nagai R, Arai M, Miyashita M, Itokawa M, Fujita T, Nangaku M. Glyoxalase-I retards renal senescence. Am J Pathol. 2011; 179: 2810-2821. | download |
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| Miyata T, Kikuchi K, Kiyomoyo H,van Ypersele de Strihou C. New era for drug discovery and development in renal disease.Nat Rev Nephrol. 2011; 7: 469-477. | download |
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| Ueno H, Koyama H, Fukumoto S, Tanaka S, Shoji T, Shoji T, Emoto M, Tahara H, Inaba M, Kakiya R, Tabata T,Miyata T, Nishizawa Y. Advanced glycation end products, carotid atherosclerosis, and circulating endothelial progenitor cells in patients with end-stage renal disease. Metabolism. 2011; 60: 453-459. | download |
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| Miyata T, Takizawa S, van Ypersele de Strihou C. Hypoxia. 1.Intracellular sensors for oxygen and oxidative stress: Novel therapeutic targets. Am J Physiol Cell Physiol. 2011; 300: 226-231. | download |
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| Brouwers O.; Niessen P.M.; Haenen G.; Miyata T.; Brownlee M.; Stehouwer C.D.; De Mey J.G.; Schalkwijk C.G. Hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation in rat mesenteric arteries is mediated by intracellular methylglyoxal levels in a pathway dependent on oxidative stress. Diabetologia.2010;53:989-1000. | download |
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| Brouwers O, Niessen PM, Ferreira I, Miyata T, Scheffer PG, Teerlink T, Schrauwen P, Brownlee M, Stehouwer CD, Schalkwijk CG. Overexpression of Glyoxalase-I Reduces Hyperglycemia–induced Levels of Advanced Glycation Endproducts and Oxidative Stress in Diabetic Rats. J Biol Chem. 2011; 286: 1374-1380. | download |
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| Arai M, Yuzawa H, Nohara I, Ohnishi T, Obata N, Iwayama Y, Haga S, Toyota T, Ujike H, Arai M, Ichikawa T, Nishida A, Tanaka Y, Furukawa A, Aikawa Y, Kuroda O, Niizato K, Izawa R, Nakamura K, Mori N, Matsuzawa D, Hashimoto K, Iyo M, Sora I, Matsushita M, Okazaki Y, Yoshikawa T, Miyata T, Itokawa M. Enhanced carbonyl stress in a subpopulation of schizophrenia. Arch Gen Psychiatry. 2010; 67: 589-597. | download |
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| Izuhara Y, Yamaoka N, Kodama H, Dan T, Takizawa S, Hirayama N, Meguro K, van Ypersele de Strihou Charles, Miyata T. A novel inhibitor of plasminogen activator inhibitor-1 provides anti-thrombotic benefits devoid of bleeding effect in non-human primates. J Cereb Blood Flow Metab. 2010; 30:904-912. | download |
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| ＊1. Miyata T, de Strihou CY. Diabetic nephropathy: a disorder of oxygen metabolism? Nat Rev Nephrol. 2010; 6: 83-95. | download |
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