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Affiliation

Professor,Tohoku University Graduate School of Medicine

Executive Advisor to the Dean

Associate Executive Vice President,Tohoku University

Vice Executive Director, Office of Research Promotion, Tohoku University

Concurrent post

Member of Royal Academy of Medicine in Belgium, Permanent (2004~)

Advisor to the President for Science and Technology Japan Agency for Medical Research and Development (2015～）

Visiting Professor, North Western University Feinberg School of Medicine (2012~)

Tokai University Visiting Professor

Biographical Sketch

Prof. Miyata was born in 1961 in Japan and took M.D. and Ph.D. at Nagoya University School of Medicine in 1986 and 1991, respectively. He is a permanent member of Royal Academy of Medicine in Belgium, a member of Executive Committee and Council in the International Society of Nephrology (ISN), and Chair of the Committee of the Strengthening the Partnership between JSN and ISN in the Japanese Society of Nephrology (JSN). Among 250 published contributions in English include the identification of genes and attendant molecular disorders in various hereditary diseases, the delineation of mechanisms involved in the genesis of diabetic nephropathy and their prevention, of the molecular abnormalities of uraemic toxicity (carbonyl stress) and their treatment, of the roles of bioactive molecules and their inhibition (PAI-1, oxygen sensor, megsin, etc). His lab currently develops a new research area that combines medical science, structural biology, chemistry, pharmacology, and computer engineering to translate several molecules identified by basic research into clinical medicine. Projects are now at preclinical stage (PAI-1 inhibitor, oxygen sensor inhibitor) or at Phase IIa clinical study (carbonyl stress inhibitor).

Awards

2002 The Japanese Society of Molecular Medicine Award

2001 Japan Foundation for Aging and Health Award
1995 Oshima Award of the Japanese Society of Nephrology

1993 Young Investigator Award of the Japanese Society of Internal Medicine

1991 Nagoya Memorial Award

Publications

 Pyridoxamine: A novel treatment for schizophrenia with enhanced carbonyl stress.Itokawa M, Miyashita M, Arai M, Dan T, Takahashi K, Tokunaga T, Ishimoto K, Toriumi K, Ichikawa T, Horiuchi Y, Kobori A, Usami S, Yoshikawa T, Amano N, Washizuka S, Okazaki Y, Miyata T.

Psychiatry Clin Neurosci. 2018;72(1):35-44.

 A null mutation in SERPINE1 protects against biological aging in humans.Khan SS, Shah SJ,Klyachko E, Baldridge AS, Eren M, Place AT, Aviv A, Puterman E, Lloyd-Jones DM, Heiman M, Miyata T, Gupta S, Shapiro AD, Vaughan DE.

Science Advances.2017;3:eaao1617.

 TGF-β-induced intracellular PAI-1 is responsible for retaining   hematopoietic stem cells in the niche.

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.

Blood.2017;130(21):2283-2294.

 PAI-1 is a critical regulator of FGF23 homeostasis.

Eren M, Place AT, Thomas PM, Flevaris P, Miyata T, Vaughan DE.

Science Advances.2017;3: e1603259

 Plasminogen activator inhibitor-1 regulates macrophage-dependent postoperative adhesion by enhancing EGF-HER1 signaling in mice.

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.

The FASEB Journal.2017 ;31:2625-2637

A small molecule inhibitor of PAI-1 protects against Doxorubicin-induced cellular senescence: molecular basis.

Ghosh AK, Rai R, Park KE, Eren M, Miyata T, Wilsbacher LD, Vaughan DE.

Oncotarget.2016; 7:72443-72457

Therapeutic potential of an orally effective small molecule inhibitor of plasminogen activator inhibitor for asthma.

Liu RM, Eldridge S, Watanabe N, Deshane J, Kuo HC, Jiang C, Wang Y, Liu G, Schwiebert L, Miyata T, Thannickal VJ.

Am J Physiol Lung Cell Mol Physiol.2016; 15: 328-336.

Novel Plasminogen Activator Inhibitor-1 Inhibitors Prevent Diabetic Kidney Injury in a Mouse Model.

Jeong BY, Uddin MJ, Park JH, Lee JH, Lee HB, Miyata T, Ha H.

PLoS One.2016; 11: e0157012.

A novel plasminogen activator inhibitor-1 inhibitor, TM5441, protects against high-fat diet-induced obesity and adipocyte injury in mice.

Piao L,Jung I, Huh JY, Miyata T, Ha H.

British J Pharmacology.2016; 173:2622-2632.

Delayed intervention with pyridoxamine improves metabolic function and prevents adipose tissue inflammation and insulin resistance in high-fat diet-induced obese mice.

Maessen DE, Brouwers O, Gaens KH, Wouters K, Cleutjens JP, Janssen BJ, Miyata T, Stehouwer CD, Schalkwijk CG.

Diabetes.2016; 65: 956-966.

Small Molecule Inhibitors of Plasminogen Activator Inhibitor-1 Elicit Anti-Tumorigenic and Anti-Angiogenic Activity.

Placencio VR, Ichimura A, Miyata T, DeClerck YA.

PLoS One.2015; 10: e0133786.

Erythropoietin Synthesis in Renal Myofibroblasts Is Restored by Activation of Hypoxia Signaling.

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.

J Am Soc Nephrol.2016; 27: 428-438.

Plasminogen Activator Inhibitor-1 Antagonist TM5484 Attenuates Demyelination and Axonal Degeneration in a Mice Model of Multiple Sclerosis.

Pelisch N, Dan T, Ichimura A, Sekiguchi H, Vaughan DE, van Ypersele de Strihou C, Miyata T.

PLoS One. 2015; 10: e0124510.

Podocyte injury-driven intracapillary plasminogen activator inhibitor type 1 accelerates podocyte loss via beta 1 integrin endocytosis.

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.

Am J Physiol Renal Physiol.2015; 308:F614-26.

PAI-1-regulated extracellular proteolysis governs senescence and survival in Klotho mice

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.

Proc Natl Acad Sci USA. 2014; 111: 7090-7095.

Drug discovery in renal disease —towards a more efficient framework

Miyata T, Ando T, Hiragi H, Watanabe K, Yamamoto F, Vaughan DE, Kurokawa T, Oshima Y, van Ypersele de Strihou C, Takeuchi M.

Nat Rev Nephrol 2014; 10: 290-296.

Inhibition of Plasminogen Activator Inhibitor Type-1 Activity Enhances Rapid and Sustainable Hematopoietic Regeneration

Ibrahim AA, Yahata T, Onizuka M, Dan T, van Ypersele de Strihou C, Miyata T, Ando K.
Stem Cells 2014; 32: 946-958.

Glyoxalase-1 overexpression reduces endothelial dysfunction and attenuates early renal impairment in a rat model of diabetes

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.
Diabetologia 2014; 57: 224-235.

The PAI-1 antagonist TM5441 attenuates L-NAME-induced

hypertension and vascular senescence
Boe A, Eren M, Murphy S, Kamide1 C, Ichimura A, Terry D, McAnally D, Smith LH, Miyata T, Vaughan DE.
Circulation 2013; 128: 2318-2324.

Kidney failure: aims for the next 10 years and barriers to success

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.

Lancet 2013; 382: 353-362.

Diabetic nephropathy: Are there new and potentially promising therapies targeting oxygen biology?

Miyata T, Suzuki N, van Ypersele de Strihou C.

Kidney Int 2013; 84: 693-702.

A Small Molecule Inhibitor to Plasminogen Activator Inhibitor 1 Inhibits Macrophage Migration

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.

Arterioscler Thromb Vasc Biol. 2013; 33: 935-942.

Metabolic stress response implicated in diabetic retinopathy:the role of calpain, and the therapeutic impact of calpain inhibitor.

Shanab AY, Nakazawa T, Ryu M, Tanaka Y, Himori N, Taguchi K, Yasuda M, Watanabe R, Takano J, Takaomi S, Minegishi N, Miyata T, Abe T, Yamamoto M.

Neurobiology of Disease 2012; 48: 556-567.

The receptor of advanced glycation end products (RAGE) plays a central role in advanced oxidation protein products-induced podocyte apoptosis.

Zhou LL, Cao W, Xie C, Tian J, Zhou Z, Zhou Q, Zhu P, Li A, Liu Y, Miyata T, Hou FF, Nie J.

Kidney Int 2012; 82 759-770

Inhibition of PAI-1 induces neutrophil-driven neoangiogenesis and promotes tissue regeneration via production of angiocrine factors in mice.

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.

Blood 2012; 119: 6382-6393.

Protection against methylglyoxal-derived AGEs by regulation of glyoxalse-1 prevents retinal neuroglial and vasodegenerative pathology.

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.

Diabetologia 2012; 55: 845-854.

Skin advanced glycation end product accumulation is negatively associated with calcaneal osteo-sono assessment index among non-diabetic adult Japanese men.
Momma H, Niu K, Kobayashi Y, Guan L, Sato M, Guo H, Chujo M, Otomo A, Yufei C, Tadaura H, Saito T, Mori T, Miyata T, Nagatomi R.

Osteoporos Int 2012; 23: 1673-1681.

Therapeutic value of small molecule inhibitor to plasminogen activator inhibitor-1 for lung fibrosis.

Huang WT, Vayalil PK, Miyata T, Hagood J, Liu RM.

Am J Respir Cell Mol Biol. 2012; 46: 87-95.

Glyoxalase-I retards renal senescence.

Ikeda Y, Inagi R, Miyata T, Nagai R, Arai M, Miyashita M, Itokawa M, Fujita T, Nangaku M.

Am J Pathol 2011; 179: 2810-2821.

New era for drug discovery and development in renal disease.

   Miyata T, Kikuchi K, Kiyomoyo H,van Ypersele de Strihou C.

   Nat Rev Nephrol 2011;7:469-477.

In Oxidative Stress in Applied Basic Research and Clinical Practice: Studies on Renal Disorders (Springer), edited by Toshio MIyata, Kai-Uwe Eckardt, Masaomi Nangaku.

Hypoxia. 1. Intracellular sensors for oxygen and oxidative stress: novel therapeutic targets.

Miyata T, Takizawa S,van Ypersele de Strihou C.

Am J Physiol Cell Physiol 2011;300:226-231.

Effect of Sevelamer and Calcium-Based Phosphate Binders on Coronary Artery Calcification and Accumulation of Circulating Advanced Glycation End Products in Hemodialysis Patients.

Kakuta T, Tanaka R, Hyodo T, Suzuki H, Kanai G, Nagaoka M, Takahashi H, Hirawa N, Oogushi Y, Miyata T, Kobayashi H, Fukagawa M, Saito A.

Am J Kidney Dis 2011;57:422-431.

Overexpression of Glyoxalase-I Reduces Hyperglycemia–induced Levels of Advanced Glycation Endproducts and Oxidative Stress in Diabetic Rats.

Brouwers O, Niessen PM, Ferreira I, Miyata T, Scheffer PG, Teerlink T, Schrauwen P, Brownlee M, Stehouwer CD, Schalkwijk CG.

J Bio Chem. 2011 ;286:1374-1380.

Enhanced carbonyl stress in a subpopulation of schizophrenia.

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.  

Arch Gen Psychiatry 2010; 67: 589-597.

Diabetic nephropathy: a disorder of oxygen metabolism?

Miyata T, van Ypersele de Strihou C.

Nat Rev Nephrol. 2010;6:83-95.

Total publications in English

Total of 234 peer-reviewed contributions in English (Total impact factor 1,192 points; Total citation factors 9,448 points; H-index is 53).

See also Research Information.