Christiane E.L. Dammann, M.D. is currently a research and clinical fellow in the Division of Newborn Medicine at New England Medical Center and a research fellow in the Division of Signal Transduction at the Beth Israel Hospital. She is applying for this award to develop a career as an independent scientist in Neonatology with her research focused on fetal lung development. She will accomplish this goal with the help of her two mentors Dr. Nielsen and Dr. Cantley. Pulmonary surfactant consists of phospholipids and apoproteins and is critical for lung maturation. Surfactant deficiency during fetal lung development contributes to neonatal distress syndrome. Fibroblast- Pneumocyte-Factor (FPF) is a fibroblast derived polypeptide differentiation factor that regulates surfactant synthesis in lung type II epithelial cells. We have strong evidence that Neuregulin-1 (NRG1), a stromal-derived growth factor previously implicated in mammary gland epithelial cell maturation, is a critical component of FPF. For our preliminary studies we have used MLE 12 cells, which display characteristics of fetal type II cells. We now propose to investigate further the role of NRGs and their receptors in regulating surfactant synthesis during lung development using primary fetal mouse cells.
The specific aims of this proposal are threefold. First, the role of the NRGs in the regulation of fibroblast-type II cell communication leading to surfactant synthesis will be determined. Second the regulation of NRG expression / production during lung development will be investigated. Third, the question which of the erbB receptors and intracellular ligands are involved in the NRG signaling pathway in mesenchymal-type II cell communication will be studied. The goal is to gain further insight into the regulation of surfactant synthesis. This should contribute to the development of diagnostic and therapeutic strategies that reduce the burden of acute and chronic lung disease among preterm infants.
| Zscheppang, Katja; Dörk, Thilo; Schmiedl, Andreas et al. (2011) Neuregulin receptor ErbB4 functions as a transcriptional cofactor for the expression of surfactant protein B in the fetal lung. Am J Respir Cell Mol Biol 45:761-7 |
| Zscheppang, Katja; Konrad, Mirja; Zischka, Melanie et al. (2011) Estrogen-induced upregulation of Sftpb requires transcriptional control of neuregulin receptor ErbB4 in mouse lung type II epithelial cells. Biochim Biophys Acta 1813:1717-27 |
| Schmiedl, Andreas; Behrens, Jan; Zscheppang, Katja et al. (2011) Lipopolysaccharide-induced injury is more pronounced in fetal transgenic ErbB4-deleted lungs. Am J Physiol Lung Cell Mol Physiol 301:L490-9 |
| Hoffmann, Insa; Bueter, Wolfgang; Zscheppang, Katja et al. (2010) Neuregulin-1, the fetal endothelium, and brain damage in preterm newborns. Brain Behav Immun 24:784-91 |
| Liu, Washa; Purevdorj, Erkhembulgan; Zscheppang, Katja et al. (2010) ErbB4 regulates the timely progression of late fetal lung development. Biochim Biophys Acta 1803:832-9 |
| 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 |
| Purevdorj, Erkhembulgan; Zscheppang, Katja; Hoymann, Heinz G et al. (2008) ErbB4 deletion leads to changes in lung function and structure similar to bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol 294:L516-22 |
| Liu, Washa; Zscheppang, Katja; Murray, Sandy et al. (2007) The ErbB4 receptor in fetal rat lung fibroblasts and epithelial type II cells. Biochim Biophys Acta 1772:737-47 |
| 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 |
| Bueter, Wolfgang; Dammann, Olaf; Zscheppang, Katja et al. (2006) ErbB receptors in fetal endothelium--a potential linkage point for inflammation-associated neonatal disorders. Cytokine 36:267-75 |
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