Masuko Ushio-Fukai

My research centers on investigating the molecular mechanism of angiogenesis, anteriogenesis and vasculogenesis, which plays an important role for development, tissue repair and regeneration as well as for treatment of ischemic cardiovascular diseases. I have a strong background in the area of redox signaling activated by Reactive Oxygen Species (ROS), angiogenesis mediated through VEGF receptor2 (VEGFR2) signaling, and post-ischemic neovascularization in physiological and pathological conditions such as diabetes and inflammation. Our laboratory demonstrated that ROS derived from NADPH oxidase (NOX) play an important role in revascularization in response to ischemic injury through regulating redox signaling in endothelial cells and bone marrow stem cell niche that coordinates stem/progenitor cell function. To determine the molecular targets of ROS mediating angiogenesis, we used newly-developed Cys-OH reactive probes to identify the Cys oxidized proteins in response to angiogenic growth factors, ischemic injury and hypoxia. Our long-term goal is to understand how highly diffusible ROS derived from NOX and Mitochondria can activate signaling at specific subcellular compartments to promote angiogenesis and tissue regenerative/repair, and how dysregulation of redox balance and signaling contributes to vascular complications in cardiovascular diseases. Moreover, we also investigate a role of Copper, an essential micronutrient, in angiogenesis and stem cell biology by focusing on Copper transport proteins and their linkage with VEGFR2 signaling, autophagy, and endothelial-mesenchymal transition. We use molecular biology, cell biology and biochemical approaches, cell imaging and signal transduction analysis, various transgenic and knockout mice models. By understanding the ROS signaling and copper transport system involved in angiogenesis, we hope to develop new therapies for treatment of patients with ischemic cardiovascular disease and cancer.

Mittal M, Urao N, Di A, Hecquet CM, Gao XP, Komarova Y, Ushio-Fukai M, Malik AB. Novel role of ROS-activated TRP Melastatin Channel-2 (TRPM2) in mediating angiogenesis and ischemic neovascularization. Arterioscler Thromb Vasc Biol. 35:877-887, 2015.

Ushio-Fukai M, Rehman J. Redox and metabolic regulation of stem/progenitor cells and their niche. Antioxid Redox Signal. 21:1587-1590, 2014.

Yamada KH, Nakajima Y, Geyer M, Wary KK, Ushio-Fukai M, Komarova Y, Malik AB. KIF13B regulates angiogenesis through Golgi-Plasma membrane trafficking of VEGFR2. J Cell Sci. 127:4518-4530, 2014.

Urao N, Sudhahar V, Kim SJ, Chen GF, McKinney RD, Koida G, Fukai T, Ushio-Fukai M. Critical role of endothelial hydrogen peroxide in post-ischemic neovascularization. PLoS One. 8:e57618, 2013.

Urao N, Ushio-Fukai M. Redox regulation of stem/progenitor cells and bone marrow niche. Free Radic Biol Med. 54:26-39, 2013. Review.

Kohler E, Wary KK, Li F, Chatterjee I, Urao N, Toth PT, Ushio-Fukai M, Rehman J, Park C, Malik AB. Flk1+ and VE-Cadherin+ Endothelial Cells derived from iPSCs Recaptulates Vascular Development during Differntiation and Display Similar Angiogenic Potential as ESC-derived Cells. PLoS One. 8:e85549, 2013.

Urao N, McKinney RD, Fukai T, Ushio-Fukai M. NADPH oxidase 2 regulates bone marrow microenvironment following hindlimb ischemia: role in reparative mobilization of progenitor cells. Stem Cells. 30:923-34, 2012.

Kaplan N, Urao N, Furuta E, Kim SJ, Razvi M, Nakamura Y, McKinney RD, Poole LB, Fukai T, Ushio-Fukai M. Localized cysteine sulfenic acid formation by vascular endothelial growth factor: role in endothelial cell migration and angiogenesis.Free Radic Res. 45:1124-35, 2011.

Urao N, Inomata H, Razvi M, Kim HW, Wary K, McKinney R, Fukai T, Ushio-Fukai M. Role of Nox2-based NADPH oxidase in bone marrow and progenitor cell function involved in neovascularization induced by hindlimb ischemia. Circ Res. 103:212-220, 2008.

Ushio-Fukai M. Localizing NADPH oxidase-derived ROS. Science STKE. 349: 1-6, 2006.