RTG 2338 Targets in Toxicology
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P05 - Systematic dissection of acute and chronic molecular consequences of neonatal hyperoxia on distinct lung alveolar cell classes

Neonatal chronic lung disease (nCLD), also known as bronchopulmonary dysplasia (BPD), is one of the major complications arising in the premature infant. Initiation of disease in the neonatal lung is driven by pre- and postnatal stressors, including the life-saving supplementation of oxygen after birth, but the underlying mechanisms are poorly understood. This project aims to analyze the impact of early postnatal hyperoxia on the developing lung, in a time- and dose-dependent manner by measuring early molecular perturbations and persistent epigenetic changes in a preclinical model. To translate the findings, patient samples will be screened to identify biomarkers that can be used in the clinical setting.

Project-related publications:


1. Oak P, Hilgendorff A. The BPD trio? Interaction of dysregulated PDGF, VEGF, and TGF signaling in neonatal chronic lung disease. Mol Cell Pediatr 2017; 4(1):11. doi: 10.1186/s40348-017-0076-8. Review.

2. Förster K, Sass S, Ehrhardt H, Mous DS, Rottier RJ, Oak P, Schulze A, Flemmer AW, Gronbach J, Hübener C, Desai T, Eickelberg O, Theis FJ, Hilgendorff A. Early Identification of Bronchopulmonary Dysplasia Using Novel Biomarkers by Proteomic Screening. Am J Respir Crit Care Med 2017 doi:10.1164/rccm.201706-1218LE (Epub ahead of print)

3. Hilgendorff A, Windhorst A, Klein M, Tchatalbachev S, Windemuth-Kieselbach C, Kreuder J, Heckmann M, Gkatzoflia A, Ehrhardt H, Mysliwietz J, Maier M, Izar B, Billion A, Gortner L, Chakraborty T, Hossain H. Gene expression profiling at birth characterizing the preterm infant with early onset infection. J Mol Med 2017; 95(2):169-180. doi: 10.1007/s00109-016-1466-4.

4. Ehrhardt H, Pritzke T, Oak P, Kossert M, Biebach L, Förster K, Koschlig M, Alvira CM, Hilgendorff A. Absence of TNF-α enhances inflammatory response in the newborn lung undergoing mechanical ventilation. Am J Physiol Lung Cell Mol Physiol. 2016; 310(10):L909-18. doi:10.1152/ajplung.00367.2015.

PD Dr. med. Anne Hilgendorff

LMU Munich and CPC Helmholtz Zentrum München