Investigating the role of circularRNA in the pathogenesis of Congenital Diaphragmatic Hernia (CDH) and exploring them as potential biomarkers in the prognostication of CDH

• Applicant: Dr. Marietta Jank
• Subject Area: Pneumology, Thoracic Surgery ; Pediatric and Adolescent Medicine
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 519368454

Congenital Diaphragmatic Hernia (CDH) is a defect in the diaphragm characterized by a herniation of abdominal organs into the thoracic cavity and concomitant abnormal lung development with varying degree of pulmonary hypoplasia and hypertension. Every day 150 infants with CDH die worldwide. Even though CDH is a rare condition, it significantly contributes to neonatal morbidity and mortality. Despite extensive intensive care management and timely surgical repair of the defect, the mortality lies by 30-50%. Precise prenatal diagnosis of CDH using the current modalities (ultrasound and MRI) remains challenging and only 70% of CDH cases are identified prenatal. CDH in a fetus is typically discovered through ultrasound screening at 20 weeks of gestation and the subsequent MRI scan aims to estimate the severity of abnormal lung development. However, these prenatal imaging modalities are imprecise in predicting the clinical management and outcome of CDH babies. To date, few validated prenatal biomarkers for congenital anomalies (e.g. trisomy 21, spina bifida) exist and none for CDH. Latest molecular biology techniques allow detection of epigenetic biomolecules including small RNA making them promising, non-invasive biomarkers in diagnostics and prognostication of various diseases. The host institution of Prof. Richard Keijzer, University of Mannitoba (Winnipeg, Canada), was the first to show a distinct biosignature of micro RNA (mirRNA) and circular RNA (circRNA) in CDH lungs and the amniotic fluid samples from women carrying a CDH fetus. In cooperation with the laboratory of Prof. Keijzer we aim to explore circRNA as possible biomarkers for CDH. The home institution, University Medical Center Mannheim, is a renown and ERNICA (European Reference Network for rare Inherited and Congenital Anomalies) – accredited center for the treatment of CDH and neonatal ECMO therapy. For over 15 years, we treat at least 50 neonates with CDH after birth every year, without considering children in the follow-up program. By combining our long-standing clinical experience as well as extensive amount of data on CDH children and Prof. Keijzer’s expertise, our goal is to create a comprehensive database and upon return biobank. Herewith, we aim to identify and validate promising biomarkers using the methods acquired in the host institution to improve diagnostics and prognostication of CDH. In consequence, the interdisciplinary team can better assess disease severity and necessity of prenatal intervention, resulting in precise medical counselling of prospective parents and better preparation of postnatal management.

• DFG Programme: WBP Fellowship
• International Connection: Canada
• Host: Professor Dr. Richard Keijzer, Ph.D.