Research
Faculty Members
Cardiovascular Science and Drug Discovery（Medical and Health Sciences）
Shirakura KeisukeAssistant professor
Blood vessels are distributed throughout the body and play essential roles in delivering oxygen and nutrients. Abnormalities in vascular structure and function are closely associated with the onset and progression of various dieseases. My research aims to elucidate the pathophysiological roles of blood vessels and to contribute to drug discovery based on these findings.
Research theme
Investigation of the Pathophysiological Roles of Mechanotransduction in Blood Vessels
Blood vessels are continuously exposed to blood flow and dynamically regulate their structure and function in response to its velocity and flow patterns. These adaptive responses are mediated by mechanotransduction systems that sense mechanical forces generated by blood flow. Dysregulation of blood flow and mechanosensing pathways contributes to the progression of cardiovascular diseases such as atherosclerosis. However, the underlying mechanisms of these systems remain poorly understood. Our goal is to elucidate mechanotransduction pathways and their roles in cardiovascular diseases, ultimately contributing to the development of novel therapeutic strategies.
Development of Brain Drug Delivery Targeting Cerebral Vasculature
Vascular permeability varies across organs. Cerebral blood vessels form the blood–brain barrier (BBB), which maintains significantly lower permeability compared to vessels in other tissues. While the BBB protects the brain from harmful substances, it also restricts the delivery of therapeutic agents, posing a major challenge for the development of treatments for neurological disorders. My research focuses on developing strategies to facilitate drug delivery to the brain by modulating the permeability of cerebral vasculature.
Representative achievements
Inoue S, Shirakura K, Shirono A, Taguchi J, Ikeda Y, Tomita S, Funatsu R, Muraoka K, Hashimoto Y, Tachibana K, Hino N, Doi T, Ikemi Y, Nunomura K, Lin B, Nakagawa S, Tsujikawa K, Tanaka S, Obana M, Fujio Y, Hosoya T, Takeda H, Kondoh M, Okada Y. ‘Claudin 5-binding small molecule transiently opens the blood-brain barrier and safely enhances brain drug delivery.’ J Control Release.
Shirakura K, Ghanbarpour Houshangi M, Peters KG, Vestweber D. ‘VE-PTP controls a fluid shear stress set point that governs cell morphological responses through Tie-2.’ Front Cell Dev Biol. 2025
Ghanbarpour Houshangi M, Shirakura K, Vestweber D. ‘Tie-2 regulates endothelial morphological responses to shear stress by FOXO1-triggered autophagy.’ PLoS One. 2025
Tanaka M, Shirakura K, Takayama Y, Μatsui M, Watanabe Y, Yamamoto T, Takahashi J, Tanaka S, Hino N, Doi T, Obana M, Fujio Y, Takayama K, Okada Y. ‘Endothelial ROBO4 suppresses PTGS2/COX-2 expression and inflammatory diseases.’ Commun Biol. 2024
Shirakura K, Baluk P, Nottebaum AF, Ipe U, Peters KG, McDonald DM, Vestweber D. ‘Shear stress control of vascular leaks and atheromas through Tie2 activation by VE-PTP sequestration.’ EMBO Mol Med. 2023
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
Shirakura K, Ishiba R, Kashio T, Sakai M, Fukushima Y, Yamamoto N, Manabe S, Shigesada N, Tanaka T, Hino N, Aird WC, Doi T, Okada Y. ‘Endothelial Robo4 regulates IL-6 production by endothelial cells and monocytes via a crosstalk mechanism in inflammation.’ Biochem Biophys Res Commun. 2018
