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 #
2R01HL053793-13A1
Application #
7526139
Study Section
Vascular Cell and Molecular Biology Study Section (VCMB)
Program Officer
Schwartz, Lisa
Project Start
1997-08-01
Project End
2008-10-31
Budget Start
2008-06-16
Budget End
2008-10-31
Support Year
13
Fiscal Year
2008
Total Cost
$91,758
Indirect Cost
Name
Dartmouth College
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
Chen, Dongying; Simons, Michael (2018) Reprogramming the Endocardium: Trials and Tribulations. Circ Res 122:913-915
Zhang, Feng; Zarkada, Georgia; Han, Jinah et al. (2018) Lacteal junction zippering protects against diet-induced obesity. Science 361:599-603
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
Dejana, Elisabetta; Hirschi, Karen K; Simons, Michael (2017) The molecular basis of endothelial cell plasticity. Nat Commun 8:14361
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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