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
Ricard, Nicolas; Simons, Michael (2014) Fox(y) regulators of VEGF receptors. Circ Res 115:683-5
Ding, Bi-Sen; Cao, Zhongwei; Lis, Raphael et al. (2014) Divergent angiocrine signals from vascular niche balance liver regeneration and fibrosis. Nature 505:97-102
Chen, Pei-Yu; Qin, Lingfeng; Tellides, George et al. (2014) Fibroblast growth factor receptor 1 is a key inhibitor of TGF? signaling in the endothelium. Sci Signal 7:ra90
Yu, Pengchun; Tung, Joe K; Simons, Michael (2014) Lymphatic fate specification: an ERK-controlled transcriptional program. Microvasc Res 96:10-5
Bono, Francoise; De Smet, Frederik; Herbert, Corentin et al. (2013) Inhibition of tumor angiogenesis and growth by a small-molecule multi-FGF receptor blocker with allosteric properties. Cancer Cell 23:477-88
Ding, Bi-Sen; Nolan, Daniel J; Guo, Peipei et al. (2011) Endothelial-derived angiocrine signals induce and sustain regenerative lung alveolarization. Cell 147:539-53
Mollmark, Jessica; Ravi, Saranya; Sun, Baiming et al. (2011) Antiangiogenic activity of rPAI-1(23) promotes vasa vasorum regression in hypercholesterolemic mice through a plasmin-dependent mechanism. Circ Res 108:1419-28
Hatanaka, Kunihiko; Simons, Michael; Murakami, Masahiro (2011) Phosphorylation of VE-cadherin controls endothelial phenotypes via p120-catenin coupling and Rac1 activation. Am J Physiol Heart Circ Physiol 300:H162-72
Murakami, Masahiro; Nguyen, Loc T; Hatanaka, Kunihiko et al. (2011) FGF-dependent regulation of VEGF receptor 2 expression in mice. J Clin Invest 121:2668-78
Tirziu, Daniela; Giordano, Frank J; Simons, Michael (2010) Cell communications in the heart. Circulation 122:928-37

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