Hilgendorff Lab

To understand the induction of injury and subsequent onset of chronic disease in the developing lung, we investigate the impact of shear stress, oxygen and other toxins on alveolar and vascular development using unique preclinical models. We focus on aberrant growth factor signaling in the context of lung development and translate our findings into clinical studies for the development of diagnostic tools and exploration of treatment strategies We address across-organ morbidity to evaluate the lung as a driver of these complications. 

The development of chronic lung disease in the neonate, also described as Bronchopulmonary Dysplasia (BPD), affects more than 30% of all infants born with a functionally and structurally immature lung. While mechanical ventilation (MV) and oxygen therapy offer live saving support after birth, they significantly contribute to disease development in this patent population at the same time.

The significant changes that characterize the disease include extensive remodeling of the extracellular matrix and sustained inflammatory changes, ultimately resulting in the formation of a simplified and dysmorphic gas exchange area. Despite the clinical significance, a profound understanding of the molecular mechanisms underlying the structural changes is still missing. Here, the need to interpret the complex interplay of deregulated growth factor signaling beyond the background organ development render this task especially challenging.

Clinically, markers that allow for the early postnatal prediction of BPD development are urgently needed, as the diagnostic process solely relies on clinical parameters derived from end-stage pulmonary function.  

Our aim is a profound understanding of the molecular mechanisms induced by pre- and postnatal injury that result in sustained changes to the gas exchange area with a focus on alveolar septation and vessel formation. We design our in vivo and in vitro models to closely mimic clinical conditions and further translate our findings by the use of our unique clinical cohort. In the AIRR (Attention to Infants at Respiratory Risks) cohort, deep-phenotyping of very immature preterm infants and term neonates with chronic lung disease include imaging strategies and lung function testing and is paired with multi-omics and AI strategies, enabling the development of new diagnostic tools for tomorrow`s clinical care. Future steps include the development of a clinical test for the biomarkers identified (patent filed) and a clinical study to implement them into clinical use.

In close collaboration within the Comprehensive Pneumology Center (CPC) and the German Center for Lung Research (DZL), we furthermore engage our knowledge in understanding adult forms of chronic lung disease that share the pattern of emphysematous changes and interstitial fibroproliferation.