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
Yu, Pengchun; Wu, Guosheng; Lee, Heon-Woo et al. (2018) Endothelial Metabolic Control of Lymphangiogenesis. Bioessays 40:e1700245
Kofler, Natalie; Corti, Federico; Rivera-Molina, Felix et al. (2018) The Rab-effector protein RABEP2 regulates endosomal trafficking to mediate vascular endothelial growth factor receptor-2 (VEGFR2)-dependent signaling. J Biol Chem 293:4805-4817
Chen, Dongying; Simons, Michael (2018) Reprogramming the Endocardium: Trials and Tribulations. Circ Res 122:913-915
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Yu, Pengchun; Wilhelm, Kerstin; Dubrac, Alexandre et al. (2017) FGF-dependent metabolic control of vascular development. Nature 545:224-228
Corti, Federico; Simons, Michael (2017) Modulation of VEGF receptor 2 signaling by protein phosphatases. Pharmacol Res 115:107-123
Chen, Pei-Yu; Qin, Lingfeng; Li, Guangxin et al. (2016) Fibroblast growth factor (FGF) signaling regulates transforming growth factor beta (TGF?)-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
Kofler, Natalie; Simons, Michael (2016) The expanding role of neuropilin: regulation of transforming growth factor-? and platelet-derived growth factor signaling in the vasculature. Curr Opin Hematol 23:260-7

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