VCKD Members


Takamune Takahashi MD, PhD

Department: Medicine


Angiogenesis, formation of new blood vessels, is a pivotal process in organogenesis and tissue regeneration, requiring ordered endothelial cell proliferation, migration, and homotypic and heterotypic intercellular adhesion. However, when angiogenesis is induced (and unregulated) in pathological conditions, it greatly contributes to the progression of disease, including cancer, diabetes, ischemic, and inflammatory disorders. Thus, definition of the intrinsic molecular controls that regulate angiogenic vessel growth promises novel therapeutic approaches for angiogenesis-associated diseases. In the recent decades, investigators have identified various endothelial cell surface receptors and their activating ligands that promote and coordinate angiogenic vessel formation. However, much less is known about the endothelial receptors that transduce "anti-angiogenic (or angiostatic)" signals, though they could be used for angiogenesis inhibition. CD148 (DEP-1/PTPeta) is a transmembrane tyrosine phosphatase which is abundantly expressed in vascular endothelial cells of various tissues. We have shown that CD148 suppresses endothelial growth factor signals and strongly inhibits endothelial cell growth in culture and in vivo. Further, we have recently found that thrombospondin-1 (TSP-1) serves as an agonistic ligand for CD148. We are currently determining: 1. the role of CD148 in postnatal angiogenesis (physiological and pathological); 2. the role of TSP-1 and CD148 interaction in angiogenesis. These efforts should explore new pathways of angiogenesis inhibition and provide a novel strategy for anti-angiogenesis therapy. Another project in the lab examines the mechanisms of diabetic renal microvascular injury. We found that loss of eNOS or SOD enzyme largely exacerbates diabetic glomerular microvascular injury in mice. The lab examines the detailed mechanisms of this using conditional as well as global knockout mouse. Last, as a primary lab of Vanderbilt O'Brien Mouse Kidney Physiology and Disease Center (MKPDC), the lab and VUIIS scientists are developing non-invasive kidney imaging techniques that enable structural, functional, and molecular assessments of mouse kidney disease in living animals.

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