Abstract

In this proposal we will characterize the expression of sprouty in renal development, murine development in general and in Wilm's tumors. We will characterize the mechanism of action of sprouty. Hence we will determine if sprouty is a growth inhibitor which may mediate some of the effects of WT1. We will determine at which steo in signaling through receptor tyrosine kinase sprouty acts. We then isolate partner proteins of spry which will lead to better idea of the molecular mechanism of sprouty. In order to determine the role of spry in normal and aberrant development we will determine in cell culture models and transgenic animals if engineered expression of spry interferes with normal renal morphogenesis. Finally to provide a critical role of sprouty as a target of WT1 important for renal development we will create knockout animals for sprouty one using conditiona cre-lox technology. Through these studies we will characterize an exciting molecule involved isgnal transduction and development. Spry may present a target for future strategies against Wilm's tumor, other malignancies and renal disorder such as polycystic kidney disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA059998-09
Application #
6489259
Study Section
Special Emphasis Panel (ZRG1-MEP (02))
Program Officer
Mietz, Judy
Project Start
1994-01-01
Project End
2005-12-31
Budget Start
2002-01-01
Budget End
2002-12-31
Support Year
9
Fiscal Year
2002
Total Cost
$322,262
Indirect Cost

  Institution

Name
Mount Sinai School of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
114400633
City
New York
State
NY
Country
United States
Zip Code
10029

  Publications

Nabet, Behnam; Ó Broin, Pilib; Reyes, Jaime M et al. (2015) Deregulation of the Ras-Erk Signaling Axis Modulates the Enhancer Landscape. Cell Rep 12:1300-13
Kuracha, Murali R; Siefker, Ed; Licht, Jonathan D et al. (2013) Spry1 and Spry2 are necessary for eyelid closure. Dev Biol 383:227-38
Hwangpo, Tracy Anh; Jordan, J Dedrick; Premsrirut, Prem K et al. (2012) G Protein-regulated inducer of neurite outgrowth (GRIN) modulates Sprouty protein repression of mitogen-activated protein kinase (MAPK) activation by growth factor stimulation. J Biol Chem 287:13674-85
Sathyanarayana, Pradeep; Dev, Arvind; Pradeep, Anamika et al. (2012) Spry1 as a novel regulator of erythropoiesis, EPO/EPOR target, and suppressor of JAK2. Blood 119:5522-31
Collins, Sam; Waickman, Adam; Basson, Albert et al. (2012) Regulation of CD4? and CD8? effector responses by Sprouty-1. PLoS One 7:e49801
Kim, M K-H; Min, D J; Rabin, M et al. (2011) Functional characterization of Wilms tumor-suppressor WTX and tumor-associated mutants. Oncogene 30:832-42
Kuracha, Murali R; Burgess, Daniel; Siefker, Ed et al. (2011) Spry1 and Spry2 are necessary for lens vesicle separation and corneal differentiation. Invest Ophthalmol Vis Sci 52:6887-97
Akbulut, Simge; Reddi, Alagarsamy L; Aggarwal, Priya et al. (2010) Sprouty proteins inhibit receptor-mediated activation of phosphatidylinositol-specific phospholipase C. Mol Biol Cell 21:3487-96
Shea, Kelly L; Xiang, Wanyi; LaPorta, Vincent S et al. (2010) Sprouty1 regulates reversible quiescence of a self-renewing adult muscle stem cell pool during regeneration. Cell Stem Cell 6:117-29
Michos, Odyssé; Cebrian, Cristina; Hyink, Deborah et al. (2010) Kidney development in the absence of Gdnf and Spry1 requires Fgf10. PLoS Genet 6:e1000809

Showing the most recent 10 out of 26 publications