I have been working on oxidative stress and redox signaling in Vascular Biology Section in Boston University School of Medicine. My current and previous projects are as follows.
– Glutaredoxin and ischemic limb vascularization. In recent years my focus is the roles of glutaredoxin-1 (Glrx) in cardiovascular disease. Glrx regulates cellular signaling and transcription by reversing protein-glutathione adducts. This relatively unexplored enzyme and its targets and function have just emerged as a significant redox signaling mechanism. We identified Glrx as an anti-angiogenic molecule which may suppress hypoxia inducible factor (HIF)-1a activation. We aim to to develop therapeutic strategy to improve poor ischemic limb vascularization in diabetes and aged individuals.
– Tumor angiogenesis: we found mouse melanoma implants growth does not correlate with endothelial angiogenesis in endothelial-specific Glrx transgenic mice. We are developing a new area of Glrx and tumor angiogenesis.
– We also explore Glrx role in liver fibrosis with my collaborators. Glrx-deficient mice develop fatty liver and diet-induced liver fibrosis. Glrx inhibits angiogenesis as well as fibrotic process. Our collaborative paper shows Glrx attenuates lung fibrosis. We aim to examine the Glrx effects on liver fibrosis models.
– In the past, I worked on vascular complications in glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD is a key enzyme of the pentose phosphate pathway which contributes to NADPH generation. G6PD deficiency is the most prevalent enzymopathy in humans, and was thought to worsen cardiovascular disease due to oxidative stress and hemolytic anemia. However, we found that angiotensin II –induced cardiovascular hypertrophy was attenuated in G6PD-deficient mice. There are many enzymes that depend on NADPH including the oxidant source, NADPH oxidase, and enzymes in the cholesterol synthesis pathway. We also demonstrated higher blood pressure, less atherosclerosis, lower oxidants and plasma cholesterol in G6PD-deficient mice with apoE-/- background. These studies are actually consistent with clinical reports on G6PD-deficient people, and confirmed a contribution of NADPH oxidase to vascular hypertrophy and atherosclerosis.
Overall, based on my broad clinical experiences in internal medicine, I would like to develop my research to bring benefit to patients.
- Boston Medical Center
- Kanazawa University, MD
- Published on 7/9/2018
Anathy V, Lahue KG, Chapman DG, Chia SB, Casey DT, Aboushousha R, van der Velden JLJ, Elko E, Hoffman SM, McMillan DH, Jones JT, Nolin JD, Abdalla S, Schneider R, Seward DJ, Roberson EC, Liptak MD, Cousins ME, Butnor KJ, Taatjes DJ, Budd RC, Irvin CG, Ho YS, Hakem R, Brown KK, Matsui R, Bachschmid MM, Gomez JL, Kaminski N, van der Vliet A, Janssen-Heininger YMW. Reducing protein oxidation reverses lung fibrosis. Nat Med. 2018 Aug; 24(8):1128-1135. PMID: 29988126.
- Published on 5/18/2017
Egea J, Fabregat I, Frapart YM, Ghezzi P, Görlach A, Kietzmann T, Kubaichuk K, Knaus UG, Lopez MG, Olaso-Gonzalez G, Petry A, Schulz R, Vina J, Winyard P, Abbas K, Ademowo OS, Afonso CB, Andreadou I, Antelmann H, Antunes F, Aslan M, Bachschmid MM, Barbosa RM, Belousov V, Berndt C, Bernlohr D, Bertrán E, Bindoli A, Bottari SP, Brito PM, Carrara G, Casas AI, Chatzi A, Chondrogianni N, Conrad M, Cooke MS, Costa JG, Cuadrado A, My-Chan Dang P, De Smet B, Debelec-Butuner B, Dias IHK, Dunn JD, Edson AJ, El Assar M, El-Benna J, Ferdinandy P, Fernandes AS, Fladmark KE, Förstermann U, Giniatullin R, Giricz Z, Görbe A, Griffiths H, Hampl V, Hanf A, Herget J, Hernansanz-Agustín P, Hillion M, Huang J, Ilikay S, Jansen-Dürr P, Jaquet V, Joles JA, Kalyanaraman B, Kaminskyy D, Karbaschi M, Kleanthous M, Klotz LO, Korac B, Korkmaz KS, Koziel R, Kracun D, Krause KH, Kren V, Krieg T, Laranjinha J, Lazou A, Li H, Martínez-Ruiz A, Matsui R, McBean GJ, Meredith SP, Messens J, Miguel V, Mikhed Y, Milisav I, Milkovic L, Miranda-Vizuete A, Mojovic M, Monsalve M, Mouthuy PA, Mulvey J, Münzel T, Muzykantov V, Nguyen ITN, Oelze M, Oliveira NG, Palmeira CM, Papaevgeniou N, Pavicevic A, Pedre B, Peyrot F, Phylactides M, Pircalabioru GG, Pitt AR, Poulsen HE, Prieto I, Rigobello MP, Robledinos-Antón N, Rodríguez-Mañas L, Rolo AP, Rousset F, Ruskovska T, Saraiva N, Sasson S, Schröder K, Semen K, Seredenina T, Shakirzyanova A, Smith GL, Soldati T, Sousa BC, Spickett CM, Stancic A, Stasia MJ, Steinbrenner H, Stepanic V, Steven S, Tokatlidis K, Tuncay E, Turan B, Ursini F, Vacek J, Vajnerova O, Valentová K, Van Breusegem F, Varisli L, Veal EA, Yalçin AS, Yelisyeyeva O, Žarkovic N, Zatloukalová M, Zielonka J, Touyz RM, Papapetropoulos A, Grune T, Lamas S, Schmidt HHHW, Di Lisa F, Daiber A. European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS). Redox Biol. 2017 10; 13:94-162. PMID: 28577489.
- Published on 5/4/2017
Matsui R, Watanabe Y, Murdoch CE. Redox regulation of ischemic limb neovascularization - What we have learned from animal studies. Redox Biol. 2017 Aug; 12:1011-1019. PMID: 28505880.
- Published on 2/16/2017
Shao D, Han J, Hou X, Fry J, Behring JB, Seta F, Long MT, Roy HK, Cohen RA, Matsui R, Bachschmid MM. Glutaredoxin-1 Deficiency Causes Fatty Liver and Dyslipidemia by Inhibiting Sirtuin-1. Antioxid Redox Signal. 2017 Aug 20; 27(6):313-327. PMID: 27958883.
- Published on 9/11/2016
Han J, Weisbrod RM, Shao D, Watanabe Y, Yin X, Bachschmid MM, Seta F, Janssen-Heininger YMW, Matsui R, Zang M, Hamburg NM, Cohen RA. The redox mechanism for vascular barrier dysfunction associated with metabolic disorders: Glutathionylation of Rac1 in endothelial cells. Redox Biol. 2016 Oct; 9:306-319. PMID: 27693992.
- Published on 6/27/2016
Gorelenkova Miller O, Behring JB, Siedlak SL, Jiang S, Matsui R, Bachschmid MM, Zhu X, Mieyal JJ. Upregulation of Glutaredoxin-1 Activates Microglia and Promotes Neurodegeneration: Implications for Parkinson's Disease. Antioxid Redox Signal. 2016 Dec 20; 25(18):967-982. PMID: 27224303.
- Published on 6/1/2016
Cohen RA, Murdoch CE, Watanabe Y, Bolotina VM, Evangelista AM, Haeussler DJ, Smith MD, Mei Y, Tong X, Han J, Behring JB, Bachschmid MM, Matsui R. Endothelial Cell Redox Regulation of Ischemic Angiogenesis. J Cardiovasc Pharmacol. 2016 Jun; 67(6):458-64. PMID: 26927696.
- Published on 5/9/2016
Watanabe Y, Murdoch CE, Sano S, Ido Y, Bachschmid MM, Cohen RA, Matsui R. Glutathione adducts induced by ischemia and deletion of glutaredoxin-1 stabilize HIF-1a and improve limb revascularization. Proc Natl Acad Sci U S A. 2016 May 24; 113(21):6011-6. PMID: 27162359.
- Published on 5/6/2016
Watanabe Y, Cohen RA, Matsui R. Redox Regulation of Ischemic Angiogenesis - Another Aspect of Reactive Oxygen Species. Circ J. 2016 May 25; 80(6):1278-84. PMID: 27151566.
- Published on 12/7/2015
Yao C, Behring JB, Shao D, Sverdlov AL, Whelan SA, Elezaby A, Yin X, Siwik DA, Seta F, Costello CE, Cohen RA, Matsui R, Colucci WS, McComb ME, Bachschmid MM. Overexpression of Catalase Diminishes Oxidative Cysteine Modifications of Cardiac Proteins. PLoS One. 2015; 10(12):e0144025. PMID: 26642319.
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