Vascular integrity is key to normal function of the organism. While much has recently been learned about factors controlling new vessel growth, maintenance of vascular integrity remains poorly understood. In the previous grant cycle we have demonstrated that FGF signaling plays a key role in maintenance of endothelial cell contacts and that disruption of this signaling leads to disintegration of the mature vasculature. Thus, FGFs appear to play a major, and a totally unexpected, role in this process. In this grant, therefore, we propose to 1) Determine which FGF receptors are involved 2) How this action is achieved. The thorough molecular understanding of this process will likely provide new tools for treatment of vascular diseases, and, potentially, cancer.

Public Health Relevance

In this grant, therefore, we propose to 1) Determine which FGF receptors are involved 2) How this action is achieved. The thorough molecular understanding of this process will likely provide new tools for treatment of vascular diseases, and, potentially, cancer.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL053793-18
Application #
8280243
Study Section
Vascular Cell and Molecular Biology Study Section (VCMB)
Program Officer
Schwartz, Lisa
Project Start
1997-08-01
Project End
2013-11-30
Budget Start
2012-06-01
Budget End
2013-11-30
Support Year
18
Fiscal Year
2012
Total Cost
$525,342
Indirect Cost
$207,915
Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Kofler, Natalie; Simons, Michael (2016) The expanding role of neuropilin: regulation of transforming growth factor-β and platelet-derived growth factor signaling in the vasculature. Curr Opin Hematol 23:260-7
Chen, Pei-Yu; Qin, Lingfeng; Li, Guangxin et al. (2016) Smooth muscle FGF/TGFβ cross talk regulates atherosclerosis progression. EMBO Mol Med 8:712-28
Chen, Pei-Yu; Qin, Lingfeng; Li, Guangxin et al. (2016) Fibroblast growth factor (FGF) signaling regulates transforming growth factor beta (TGFβ)-dependent smooth muscle cell phenotype modulation. Sci Rep 6:33407
Chen, Pei-Yu; Simons, Michael (2016) When endothelial cells go rogue. EMBO Mol Med 8:1-2
Deng, Yong; Zhang, Xi; Simons, Michael (2015) Molecular controls of lymphatic VEGFR3 signaling. Arterioscler Thromb Vasc Biol 35:421-9
Chen, Pei-Yu; Qin, Lingfeng; Baeyens, Nicolas et al. (2015) Endothelial-to-mesenchymal transition drives atherosclerosis progression. J Clin Invest 125:4514-28
Duncan, Daniel R; Chen, Pei-Yu; Patterson, Joseph T et al. (2015) TGFβR1 inhibition blocks the formation of stenosis in tissue-engineered vascular grafts. J Am Coll Cardiol 65:512-4
Eelen, Guy; de Zeeuw, Pauline; Simons, Michael et al. (2015) Endothelial cell metabolism in normal and diseased vasculature. Circ Res 116:1231-44
Simons, Michael; Eichmann, Anne (2015) Molecular controls of arterial morphogenesis. Circ Res 116:1712-24
Chen, Pei-Yu; Qin, Lingfeng; Tellides, George et al. (2014) Fibroblast growth factor receptor 1 is a key inhibitor of TGFβ signaling in the endothelium. Sci Signal 7:ra90

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