Under the guidance of her mentor, Dr. Heber Nielson, Dr. Volpe has developed independent research hypotheses addressing the role of Hox genes in normal and abnormal development. Her past studies have provided the focus for this current application. Dr. Volpe's immediate career goals involve establishing a career combining basic cell and molecular research in developmental lung biology with clinical care of premature infants (neonatology). This will be accomplished by further development and progress on the experiments she has outlined in this proposal. With the development of expertise and fostering of research collaborations in developmental and molecular biology, she is now at a point in her research career when focused time and effort in bench research and intensive educational studies in molecular biology and developmental biology, she is now at a point in her research career when focused time and effort in bench research and intensive educational studies in through this award will allow her to achieve these goals. Towards this purpose, Dr. Volpe will have Dr. Heber Nielson as he primary mentor, Dr. John Castellot as co-mentor, with advisory consultant support from Dr. Wellington Cardoso and Dr. Mala Chinoy. Hypothesis: Hoxb-5 affects lung patterning during branching morphogenesis through coordination of local morphogenetic signals. This hypothesis will be addressed by the following three Specific Aims.
Specific Aim #1 : Test to remodel airway patterning during branching morphogenesis.
Specific Aim #2 : Test the hypothesis that Hoxb-5 coordinates regional changes in morphogenetic signals during airway patterning through control of local cell-cell contacts and extracellular matrix (ECM) composition.
Specific Aim #3 : Test the hypothesis that Hoxb-5 regulates the interactive tension between retinoic acid and fibroblast growth factor 10 (FGF-10) to establish airway patterning during lung morphogenesis. The proposed research studies testing these hypothesis will further the understanding of the molecular mechanisms involved in normal lung development and ultimately aid in the creation of new strategies to treat neonatal lung diseases.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HD044784-04
Application #
7392177
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Javois, Lorette Claire
Project Start
2005-01-01
Project End
2010-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
4
Fiscal Year
2008
Total Cost
$129,870
Indirect Cost
Name
Tufts University
Department
Type
DUNS #
079532263
City
Boston
State
MA
Country
United States
Zip Code
02111
Volpe, MaryAnn V; Ramadurai, Sujatha M; Mujahid, Sana et al. (2013) Regulatory interactions between androgens, Hoxb5, and TGF ? signaling in murine lung development. Biomed Res Int 2013:320249
Liu, Washa; Volpe, Mary Ann V; Zscheppang, Katja et al. (2009) ErbB4 regulates surfactant synthesis and proliferation in adult rat pulmonary epithelial cells. Exp Lung Res 35:29-47
Volpe, Maryann V; Chung, Eunice; Ulm, Jason P et al. (2009) Aberrant cell adhesion molecule expression in human bronchopulmonary sequestration and congenital cystic adenomatoid malformation. Am J Physiol Lung Cell Mol Physiol 297:L143-52
Volpe, MaryAnn Vitoria; Wang, Karen Ting Wai; Nielsen, Heber Carl et al. (2008) Unique spatial and cellular expression patterns of Hoxa5, Hoxb4, and Hoxb6 proteins in normal developing murine lung are modified in pulmonary hypoplasia. Birth Defects Res A Clin Mol Teratol 82:571-84
Zscheppang, Katja; Liu, Washa; Volpe, Maryann V et al. (2007) ErbB4 regulates fetal surfactant phospholipid synthesis in primary fetal rat type II cells. Am J Physiol Lung Cell Mol Physiol 293:L429-35
Volpe, MaryAnn V; Ramadurai, Sujatha M; Pham, Lucia D et al. (2007) Hoxb-5 down regulation alters Tenascin-C, FGF10 and Hoxb gene expression patterns in pseudoglandular period fetal mouse lung. Front Biosci 12:860-73