Utilizing the Drosophila heart to model patient genomic aberrations

Together with the Einstein BIH Visiting Fellow Prof. Dr. Bodmer (SBMRI in La Jolla, CA, USA) we established a gene discovery program in the Drosophila model to test and validate genes and pathways, which we found associated with congenital heart disease (CHD) in our patient genomic screens. In particular, we focus on genes potentially causative for Tetralogy of Fallot (TOF, Grunert et al. 2014 and 2016).

Congenital heart diseases are the most common defect present in almost 1% of all human births, which in adults often results in undefined cardiac insufficiencies and arrhythmia long-term. Despite its prevalence and impact on society, our ability to identify the etiology of most CHD cases is limited. There is a great unmet need to understand the genetic mechanisms leading to developmental defects to counter the long-term clinical threats.

By using CHD patient genomic information, we aim to identify relevant novel genes that lead to CHD pathogenesis. We hope to achieve this by modeling patient-derived genetic aberrations and potentially damaging variants in the genetically versatile Drosophila model with a heart of remarkably conserved properties and controls. The significance of this project lies in the efficient discovery of new CHD genes, their polygenic interactions, mechanisms of action and placement in interlinked pathways – in vivo. The discoveries should ultimately be for the benefit of personalized patient care.