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Lung development

Linking basic science to clinical questions. Robbert Rottier

The lung development group is part of the department of Pediatric Surgery of the Sophia Children’s Hospital, a NFU recognized Center of Excellence for pediatric surgical index diagnoses (Dept. Head Prof Rene Wijnen). The Sophia Children’s Hospital is a referral center for major congenital anomalies, among which are foregut anomalies, like congenital diaphragmatic hernia (CDH), pulmonary hypertension of the newborn (PHN), Alveolar Capillary Dysplasia (ACD) and esophageal atresia with tracheoesophageal fistulas (EA/TOF). In addition, increasing interest has extended towards the Pediatric lung disease, Bronchopulmonary Dysplasia (BPD), which is an injury of the lung due to (extreme) prematurity. The Principal Investigator of the lung development group is Robbert Rottier, and was initiated in the 90’s of the last century by Prof Dick Tibboel. The laboratory is embedded within the department of Cell Biology and is an integral part of three Academic Centers of Excellence (ACE): Systems Biomedicine, Anatomical Congenital Malformations, and Pulmonary Hypertension. The overall aim of the research is to improve our understanding of foregut abnormalities by studying lung development in health and disease.
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 Legend: Dr Rottier’s research group, image taken on 29th March 2017


Characteristic histology of four pulmonary vascular disease samples.
Hematoxylin and eosin staining of human lungs: control, idiopathic pulmonary hypertension (iPAH), congenital diaphragmatic hernia (CDH), alveolar capillary dysplasia (ACD) and bronchopulmonary dysplasia (BPD). Scale bars 100µm. iPAH: thickening of the arteries (arrows), CDH: excessive muscularisation of the arteries (arrows), ACD: medial hypertrophy and muscularisation (#), malpositioning of the pulmonary veins (*) and central positioning of the capillaries in the alveolar septa, BPD: fibrosis with widening of the alveolar septa. (Kool et al, 2014)


Within the scope of this general aim, several lines of research are currently pursued, which partly overlap:

1: How does the airway epithelium differentiate and regenerate?
This links early developmental defects with adult chronic lung disorders, which is increasingly recognized as an important issue.

2: What is the origin of the pulmonary vascular changes and are there possible overlapping pathways between different pulmonary vascular diseases?

3: What is the interaction between diaphragm muscle cells and the supportive cells?
CDH is characterized by structural abnormalities of the diaphragm, which results in the presence of abdominal organs in the thoracic cavity. This may provide insights in the relation between the diaphragm defect and the lung abnormalities observed in CDH patients.

4:What is the role of lung mesenchymal stem cells and the lung microbiome in modulating lung development?

5: What do airways of BPD patients and COPD patients have in common?
This relates to the observations that early events in life that cause pediatric lung disease, increases the susceptibility to develop chronic lung disease later in life. This project is in collaboration with prof Hiemstra (LUMC) and Dr Hylkema (UMCG).


Our research is also related to the notion that early events leading to pre – and perinatal lung diseases, result in lungs that are susceptible to develop chronic lung diseases later in life. Importantly, chronic lung disorders, such as chronic obstructive pulmonary disease (COPD) and asthma, affect an estimated one million patients in the Netherlands. Strikingly, all lung-associated diseases combined, including respiratory infections and lung cancer, surpass cardiovascular disease as the main cause of death according to WHO health statistics.

Theoretical Model of Changes in FEV1 in Survivors of Bronchopulmonary Dysplasia and Healthy Subjects According to Age. (Baraldi and Filippone, 2007)

Group leader: Robbert Rottier.

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