Mechanism of Neonatal Chronic Lung Disease (Hilgendorff Lab)

Understanding mechanisms of neonatal chronic lung disease

Our mission in a nutshell....

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. 

Background - the clinical and scientific challenge

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 area1. 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 scientific direction and aims

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 2 models to closely mimic clinical conditions and further translate our findings by the use of our unique clinical cohort. In the AIRR3 (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.

Collaborations – an ever expanding network

The group is embedded in the research environment of the German Center for Lung Research (DZL) https://www.dzl.de/en/ and the Toxicology Research school https://www.grk2338.med.uni-muenchen.de/index.html.

We work in closest collaboration with our local, national and international clinical and scientific partners:

- Department of Neonatology, Perinatal Center Grosshadern, LMU Hospital http://www.klinikum.uni-muenchen.de/Kinderklinik-und-Kinderpoliklinik-im-Dr-von-Haunerschen-Kinderspital/en/stationen/neonatologie-gh/index.html

- Department for Clinical Radiology, Grosshadern, LMU Hospital  http://www.klinikum.uni-muenchen.de/International-Patient-Office/en/departments/clinical-radiology/index.html

- Institute for Computational Biology, HMGU
https://www.helmholtz-muenchen.de/icb/index.html

 PROT HMGU
https://www.helmholtz-muenchen.de/proteinscience/index.html

- Dr. Regina Feederle / MAB Monoclonal Antibody Core Facility/ Helmholtz Zentrum München - German Research Center for Environmental Health.

https://www.helmholtz-muenchen.de/mab/platform/staff/mitarbeiter/ma/5583/Dr.-Feederle/index.html

- Dr. Li Deng / VIRO Institute of Virology / HMGU Helmholtz Zentrum München - German Research Center for Environmental Health

https://www.helmholtz-muenchen.de/viro/institute/about-us/staff/staff/ma/6317/Dr.-Deng/index.html

- Prof. M. Rabinovitch and Prof. D. Bland/ Rabinovitch laboratory for Cardiopulmonary Research/ Department of Pediatrics, Division of Cardiology. Stanford Medicine

http://med.stanford.edu/rabinovitchbland.html

- Prof. Jen Sucre / School of Medicine/Vanderbilt University

https://medschool.vanderbilt.edu/evresearch/person/jennifer-sucre/

- Prof. Edda Spiekerkoetter/ Department of Medicine -Med/Pulmonary and Critical Care Medicine/ Stanford

https://profiles.stanford.edu/edda-spiekerkoetter

 - Prof. Tushar Desai/ Chest Clinic/ Stanford

https://profiles.stanford.edu/tushar-desai

- Dr. Rory Morty / Morty Lab/ Max Planck Institute for Heart and Lung Research

https://mpi-hlr.de/en/forschung/dept-iv/morty-lab/

 - Doris Hammerschmidt

https://www.cpc-munich.de/lungenforschung-360/beatmung-von-fruehgeborenen-fluch-und-segen-zugleich/index.html

https://www.cpc-munich.de/forschungsprojekte/lungenschaeden-bei-fruehgeborenen/index.html

- Dr. Carola Voss

https://www.helmholtz-muenchen.de/ilbd/the-institute/staff/index.html