Endothelial cell phenotypes display remarkable heterogeneity in health and disease. An important goal in vascular biology is to understand the molecular mechanisms underlying the spatial and temporal modulation of endothelial cell phenotypes. We have recently demonstrated that: 1) forkhead transcription factors are constitutively expressed in endothelial cells, 2) VEGF, TNF-a and thrombin induce the phosphorylation of 1 or more of the forkhead proteins in primary human endothelial cells, and 3) the inducible phosphorylation of forkhead transcription factors is coupled to a reduction in target gene expression and alteration in endothelial cell function. Taken together, this data supports the hypothesis that forkhead transcription factors function as signal transducers in the endothelium, coupling short-term changes in the extracellular environment to downstream changes in gene expression. The overall goal of this project is to characterize the role for forkhead transcription factors in transducing extracellular signals within the endothelium. A more complete understanding of these mechanisms should provide a framework for tailoring and fine tuning therapeutic modalities in vascular disease states.
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| Abid, Md Ruhul; Nadeau, Robert J; Spokes, Katherine C et al. (2008) Hepatocyte growth factor inhibits VEGF-forkhead-dependent gene expression in endothelial cells. Arterioscler Thromb Vasc Biol 28:2042-8 |
| Yano, Kiichiro; Okada, Yoshiaki; Beldi, Guido et al. (2008) Elevated levels of placental growth factor represent an adaptive host response in sepsis. J Exp Med 205:2623-31 |
| Ganopolsky, J G; Abid, Md R; Aird, W C et al. (2008) GAS6-induced signaling in human endothelial cells is mediated by FOXO1a. J Thromb Haemost 6:1804-11 |
| Abid, Md Ruhul; Spokes, Katherine C; Shih, Shou-Ching et al. (2007) NADPH oxidase activity selectively modulates vascular endothelial growth factor signaling pathways. J Biol Chem 282:35373-85 |
| Abid, Md Ruhul; Shih, Shu-Ching; Otu, Hasan H et al. (2006) A novel class of vascular endothelial growth factor-responsive genes that require forkhead activity for expression. J Biol Chem 281:35544-53 |
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