Research
Faculty Members
Clinical Science and Biomedicine（Medical and Health Sciences）
Okada YoshiakiAssociate professor
Blood vessels are not just "tubes" that carry oxygen and nutrients, but play an important role in inducing organ functions and controlling the pathology of diseases. Our team is developing research to create new drugs based on the knowledge gained from vascular biology. We would like to propose new treatment methods for diseases such as severe infectious diseases / inflammatory diseases, brain diseases, and cancer.
Research theme
Development of medicines to treat severe infectious and inflammatory diseases
Blood vessels control the movement of substances and cells between blood and organs by changing permeability. However, vascular hyperpermeability exacerbates symptoms of infectious and inflammatory diseases, and cancer. We are investigating whether these diseases can be treated by suppressing the vascular permeability.
Development of medicine that efficiently delivers drugs to the brain
The permeability of blood vessels varies from organ to organ. Blood vessels in the brain are kept less permeable than blood vessels in other organs. This function is called the blood-brain barrier and protects the brain. However, the blood-brain barrier interferes with the delivery of medicines to the brain, thus hindering the treatment of brain diseases. Therefore, we are developing a technology that temporarily controls the function of the blood-brain barrier and promotes the delivery of drugs to the brain.
Development of medicine to treat fibrosis of organs
When organs are damaged by inflammation, the organ becomes fibrotic due to the proliferation of fibroblasts. Fibrosis reduces the function of organs but does not heal spontaneously, thus reducing the patient's quality of life. We are developing a medicine that restores fibrotic organs by utilizing blood vessels.
Representative achievements
Morita M, Yoneda A, Tokunoh N, Masaki T, Shirakura K, Kinoshita M, Hashimoto R, Shigesada N, Takahashi J, Tachibana M, Tanaka S, Obana M, Hino N, Ikawa M, Tsujikawa K, Ono C, Matsuura Y, Kidoya H, Takakura N, Kubota Y, Doi T, Takayama K, Yoshioka Y, Fujio Y, Okada Y. Upregulation of Robo4 expression by SMAD signaling suppresses vascular permeability and mortality in endotoxemia and COVID-19 models. Proc Natl Acad Sci U S A. 2023;120(3):e2213317120.
Hashimoto R, Takahashi J, Shirakura K, Funatsu R, Kosugi K, Deguchi S, Yamamoto M, Tsunoda Y, Morita M, Muraoka K, Tanaka M, Kanbara T, Tanaka S, Tamiya S, Tokunoh N, Kawai A, Ikawa M, Ono C, Tachibana K, Kondoh M, Obana M, Matsuura Y, Ohsumi A, Noda T, Yamamoto T, Yoshioka Y, Torisawa YS, Date H, Fujio Y, Nagao M, Takayama K, Okada Y. SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression. Sci Adv. 2022;8(38):eabo6783.
Shirakura K, Ishiba R, Kashio T, Funatsu R, Tanaka T, Fukada SI, Ishimoto K, Hino N, Kondoh M, Ago Y, Fujio Y, Yano K, Doi T, Aird WC, Okada Y. The Robo4-TRAF7 complex suppresses endothelial hyperpermeability in inflammation. J Cell Sci. 2019;132(1).
Tanaka T, Izawa K, Maniwa Y, Okamura M, Okada A, Yamaguchi T, Shirakura K, Maekawa N, Matsui H, Ishimoto K, Hino N, Nakagawa O, Aird WC, Mizuguchi H, Kawabata K, Doi T, Okada Y. ETV2-TET1/TET2 Complexes Induce Endothelial Cell-Specific Robo4 Expression via Promoter Demethylation. Sci Rep. 2018;8(1):5653.
Okada Y, Funahashi N, Tanaka T, Nishiyama Y, Yuan L, Shirakura K, Turjman AS, Kano Y, Naruse H, Suzuki A, Sakai M, Zhixia J, Kitajima K, Ishimoto K, Hino N, Kondoh M, Mukai Y, Nakagawa S, García-Cardeña G, Aird WC, Doi T. Endothelial cell-specific expression of roundabout 4 is regulated by differential DNA methylation of the proximal promoter. Arterioscler Thromb Vasc Biol. 2014;34(7):1531-8.
Yoshikawa M, Mukai Y, Okada Y, Tsumori Y, Tsunoda S, Tsutsumi Y, Aird WC, Yoshioka Y, Okada N, Doi T, Nakagawa S. Robo4 is an effective tumor endothelial marker for antibody-drug conjugates based on the rapid isolation of the anti-Robo4 cell-internalizing antibody.
Blood. 2013;121(14):2804-13.
Baek KH, Zaslavsky A, Lynch RC, Britt C, Okada Y, Siarey RJ, Lensch MW, Park IH, Yoon SS, Minami T, Korenberg JR, Folkman J, Daley GQ, Aird WC, Galdzicki Z, Ryeom S. Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1. Nature. 2009;459(7250):1126-30.
Yano K, Okada Y, Beldi G, Shih SC, Bodyak N, Okada H, Kang PM, Luscinskas W, Robson SC, Carmeliet P, Karumanchi SA, Aird WC. Elevated levels of placental growth factor represent an adaptive host response in sepsis. J Exp Med. 2008;205(11):2623-31.
Okada Y, Jin E, Nikolova-Krstevski V, Yano K, Liu J, Beeler D, Spokes K, Kitayama M, Funahashi N, Doi T, Janes L, Minami T, Oettgen P, Aird WC. A GABP-binding element in the Robo4 promoter is necessary for endothelial expression in vivo. Blood. 2008;112(6):2336-9.
Okada Y, Yano K, Jin E, Funahashi N, Kitayama M, Doi T, Spokes K, Beeler DL, Shih SC, Okada H, Danilov TA, Maynard E, Minami T, Oettgen P, Aird WC. A three-kilobase fragment of the human Robo4 promoter directs cell type-specific expression in endothelium. Circ Res. 2007;100(12):1712-22.
