Abstract

In the first cycle of this P01, our collective and synergistic efforts have clearly established the validity of our central hypothesis that """"""""excessive TGFB signaling plays a key role in the pathobiology of the neonatal chronic lung injury termed BPD"""""""". The logical extension of these findings """"""""what's upstream and downstream of TGF in chronic neonatal lung injury and are there any useful therapeutic targets in this pathway?"""""""" is a key question that will be the focus of this revised renewal application. Thus, we propose a research program to address the following 5 inter-related, mutually reinforcing and synergistic aspects of this key question. Project 1. Warburton and Gauldie. Excess TGFB in neonatal lung injury and repair. Project 2. Minoo. BPD: interactions between inflammation and morphogenesis. Project 3. Derynck. Non-Smad mechanisms of TGFB signaling Project 4. Groffen. Negative regulation of lung inflammation by Abr/Bcr. Project 5. Bellusci. FGFR2b pathway in Bronchopulmonary Dysplasia.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL060231-08
Application #
7228094
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Blaisdell, Carol J
Project Start
1998-04-01
Project End
2010-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
8
Fiscal Year
2007
Total Cost
$1,781,539
Indirect Cost

  Institution

Name
Children's Hospital of Los Angeles
Department
Type
DUNS #
052277936
City
Los Angeles
State
CA
Country
United States
Zip Code
90027

  Publications

Buckley, Susan; Shi, Wei; Xu, Wei et al. (2015) Increased alveolar soluble annexin V promotes lung inflammation and fibrosis. Eur Respir J 46:1417-29
Xing, Yiming; Wang, Runming; Li, Changgong et al. (2015) PTEN regulates lung endodermal morphogenesis through MEK/ERK pathway. Dev Biol 408:56-65
Li, Changgong; Li, Aimin; Xing, Yiming et al. (2013) Apc deficiency alters pulmonary epithelial cell fate and inhibits Nkx2.1 via triggering TGF-beta signaling. Dev Biol 378:13-24
Gong, Dapeng; Fei, Fei; Lim, Min et al. (2013) Abr, a negative regulator of Rac, attenuates cockroach allergen-induced asthma in a mouse model. J Immunol 191:4514-20
Gong, Dapeng; Shi, Wei; Yi, Sun-ju et al. (2012) TGF? signaling plays a critical role in promoting alternative macrophage activation. BMC Immunol 13:31
El-Hashash, Ahmed H K; Turcatel, Gianluca; Varma, Saaket et al. (2012) Eya1 protein phosphatase regulates tight junction formation in lung distal epithelium. J Cell Sci 125:4036-48
Xu, Pinglong; Liu, Jianming; Derynck, Rik (2012) Post-translational regulation of TGF-* receptor and Smad signaling. FEBS Lett 586:1871-84
Tiozzo, Caterina; Danopoulos, Soula; Lavarreda-Pearce, Maria et al. (2012) Embryonic epithelial Pten deletion through Nkx2.1-cre leads to thyroid tumorigenesis in a strain-dependent manner. Endocr Relat Cancer 19:111-122
Lamouille, Samy; Connolly, Erin; Smyth, James W et al. (2012) TGF-?-induced activation of mTOR complex 2 drives epithelial-mesenchymal transition and cell invasion. J Cell Sci 125:1259-73
Xu, Pinglong; Liu, Jianming; Sakaki-Yumoto, Masayo et al. (2012) TACE activation by MAPK-mediated regulation of cell surface dimerization and TIMP3 association. Sci Signal 5:ra34

Showing the most recent 10 out of 126 publications