Elucidating the pathogenesis of retinopathies
The D’Amore laboratory has a long-standing interest in the regulation of vascular development and pathology. One major area has involved investigating the role and regulation of VEGF in adult vascular and non-vascular cells. More recently, her laboratory has been examining the role of inflammation in the pathogenesis of age-related macular degeneration. The laboratory is currently focused in three general areas. Two of those relate to understanding the molecular basis of blood vessel stabilization. One project is examining the role of Notch signaling in the stabilization of the microvasculature and the effect of diabetes on this signaling. A related project is aimed at elucidating other mechanisms that may mediate pericyte stabilization of the capillaries and how they are influenced by the diabetic milieu. Studies in both research areas are utilizing genetic model as well as tissues culture systems. A second project is examining a novel endothelial-specific molecule endomucin in the regulation of leukocyte-endothelial interactions, a central and early step in the inflammatory process. A third research focus deals with the contribution of inflammation in the pathogenesis of age-related macular degeneration and involves studying the role of the inflammasome in the retinal pigment epithelium.
1. Walshe TE, dela Paz NG, D’Amore PA. The role of shear-induced transforming growth factor-ß signaling in the endothelium. Arterio Thromb Vasc Biol, Nov. 2013; 33:2608-2617. PMID: 23968981. Ramsauer M, D’Amore PA. (2007) Contextual role for angiopoietins and TGFß1 in blood vessel stabilization. J Cell Sci, 120:1810-1817.
2. Paz NG, Walshe TE, Leach LL, Saint-Geniez M, D’Amore PA. Role of shear-stress-induced VEGF expression in endothelial cell survival. J Cell Sci, 2012,125: 831-843. PMCID: PMC3311927.
3. Tseng WA, Thein T, Kinnunen K, Lashkari K, Gregory MS, D’Amore PA*, Ksander BR*. NLRP3 inflammasome activation in retinal pigment epithelial cells by lysosomal destabilization: implications for age-related macular degeneration. Invest Ophthalmol Vis Sci. 2013; 54:110-120. PMCID: PMC3544415. (*co-senior authors)
4. Walshe TE, Dole VS, Maharaj ASR, Patten IS, Wagner DD, D’Amore PA. Inhibition of VEGF or TGF- signaling activates endothelium and increases leukocyte rolling. Arterioscler Thromb Vasc Biol, 2009, 29(8):1185-92. Epub 2009 May 21. PMCID: PMC2775449.