The research group is part of the Pediatric Surgery Department of the Sophia Children’s Hospital, and embedded within the Cell Biology Department to allow access to all the facilities. The Sophia Children’s Hospital is a referral center for major congenital anomalies, among which are lung-related diseases, like congenital diaphragmatic hernia (CDH), persistent pulmonary hypertension of the newborn (PPHN) and esophageal atresia with tracheoesophageal fistulas (EA/TOF). The lung occupies the thoracic cavity and originates as a derivative of the primitive gut, which arises when a crescent of endodermal cells starts to fold into a tubular structure after gastrulation. The rostral part, the foregut, gives rise to a number of structures, like the thyroid, lung and liver by a process called budding. The lung starts to develop when a group of ventrally located epithelial foregut cells form a small bud, which invaginates the surrounding mesenchyme. The mesenchyme secretes inducing factors to guide the repetitive branching and growth of the developing airway, a process generally called branching morphogenesis, which leads to the highly ordered bronchial tree of the lung. Although a number of important genes involved in early development of the lung have been isolated, no “master gene” has been identified, yet.

Our research interests are primarily, but not solely, focused on lung development and are driven by clinical related questions. It covers the initiation of lung development, the interaction between the circulatory and respiratory systems and the differentiation of lung epithelium. The understanding of these basic processes may lead to a better understanding of the pathogenesis of disorders, like CDH, PPHN and EA/TOF, and may contribute to an improvement of the treatment of patients with congenital lung abnormalities.

Schematic representation of normal (A) and abnormal (B) development of the foregut and genes involved in abnormal phenotypes. (A) Normal development of the foregut. (B) Genes involved in abnormal development of the foregut, resulting in EA 1 TEF. F, foregut; L, lung; LB, lung bud; E, esophagus; T, trachea; S, stomach; TEF, tracheoesophageal fistula; EA, esophageal atresia; LP, abnormal lung phenotype; GA, gestational age; *lung phenotype present; **deletion in a single case.

 

early stages of lung development (Maeda et al, 2007)

Representative pictures of embryonic lungs at day 9.5 (A), 10.5 (B), 11.5 (C) and 12.5 (D). A: Tie2-driven LacZ expression in whole mount transgenic lung shows continuity of the primitive lung vasculature with the aortic arch and the dorsal aorta.