The Expression Core will determine the developmental times and tissues in which candidate genes identified by Projects I, II and III are expressed. These studies will determine both RNA and/or protein expression patterns using immunohistochemistry or in situ hybridiation, whichever is deemed appropriate. Further, genes of particular interest will undergo analysis using the RCAS-TVA system for tissue expression of both wildtype and dominant negative proteins. Diaphragm whole mounts are difficult to examine, but the director and staff of this core have learned the necessary techniques from Dr. Akerman. Lung organ culture has been in use in the lab for 20 years. RNAi technology has been used by the Pis for the past 8 years. Together with the Drosophila Core, RNAi technology will be uniquely available for the program project. Brief descriptions of the protocols that Dr. Loscertales uses routinely which will be instrumental in analyzing CDH candidate genes follow.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD068250-03
Application #
8515488
Study Section
Special Emphasis Panel (ZHD1-DSR-N)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
3
Fiscal Year
2013
Total Cost
$95,939
Indirect Cost
$47,920
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Loscertales, Maria; Nicolaou, Fotini; Jeanne, Marion et al. (2016) Type IV collagen drives alveolar epithelial-endothelial association and the morphogenetic movements of septation. BMC Biol 14:59
High, Frances A; Bhayani, Pooja; Wilson, Jay M et al. (2016) De novo frameshift mutation in COUP-TFII (NR2F2) in human congenital diaphragmatic hernia. Am J Med Genet A 170:2457-61
Sanford, Ethan L; Choy, Kwong W; Donahoe, Patricia K et al. (2016) MiR-449a Affects Epithelial Proliferation during the Pseudoglandular and Canalicular Phases of Avian and Mammal Lung Development. PLoS One 11:e0149425
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Lundby, Alicia; Rossin, Elizabeth J; Steffensen, Annette B et al. (2014) Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics. Nat Methods 11:868-74
Lage, Kasper (2014) Protein-protein interactions and genetic diseases: The interactome. Biochim Biophys Acta 1842:1971-1980
Longoni, Mauro; High, Frances A; Russell, Meaghan K et al. (2014) Molecular pathogenesis of congenital diaphragmatic hernia revealed by exome sequencing, developmental data, and bioinformatics. Proc Natl Acad Sci U S A 111:12450-5
Lage, Kasper; Greenway, Steven C; Rosenfeld, Jill A et al. (2012) Genetic and environmental risk factors in congenital heart disease functionally converge in protein networks driving heart development. Proc Natl Acad Sci U S A 109:14035-40
Ackerman, Kate G; Vargas, Sara O; Wilson, Jay A et al. (2012) Congenital diaphragmatic defects: proposal for a new classification based on observations in 234 patients. Pediatr Dev Pathol 15:265-74
Lundby, Alicia; Lage, Kasper; Weinert, Brian T et al. (2012) Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns. Cell Rep 2:419-31

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