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Massimo M. Santoro

Laboratory of Endothelial Molecular Biology

The development, function, and remodeling of the vasculature is closely linked to the metabolic needs of the tissues it serves, regardless if that tissue is an essential organ or a pathological abnormality such as a tumor. Such metabolic requirements influence the redox state of vascular cells providing an unique mode to identify and study the antioxidant mechanisms required to balance redox homeostasis in endothelial and smooth muscle cells. Reciprocally, redox state in vascular cells may influence metabolism. Understanding this relationship is crucial to develop new therapies to cure pathological and tumor angiogenesis.

Tools to investigate the complexity of redox and metabolic interactions amongst different tissues in vivo have only recently become available, such as ratiometric redox sensors, metabolic flux analyses, and vertebrate model systems. Our goal is to expand the current knowledge of how metabolism regulates endothelial redox homeostasis and vice-versa in healthy and diseased conditions. To accomplish this we have taken advantage of the innovative genetic and imaging technology as well as new molecular and biochemical approaches in vertebrate models, including zebrafish and mouse.

We recently identified a new antioxidant gene, called UBIAD1, which is located in the isoprenoid pathway where it contributes to the maintenance of the redox balance in cardiovascular tissues. We are currently investigating how prenol lipid metabolism, endothelial dynamics, and redox regulation converge during normal development and homeostasis. Our group plan is to manipulate the Ubiad1-mediated antioxidant response in endothelial cells to modulate angiogenesis in pathological conditions (e.g. tumor formation and progression).


Karen Vousden, Paolo Sassone-Corsi, Christian Frezza, Nika Danial
12/09/2017 - 09:00