Collaboration paper at DMM
09 June 2023
June. 2023. Our most recent collaborative paper with Drs Colas and Ocorr (Sanford Burnham Prebys Medical Discovery Institute, La Jolla) is online at Disease Models & Mechanisms. Congrats to the team!
We integrated a multiplatform modeling of atrial fibrillation by combining 1) human iPSC-derived atrial-like cardiomyocytes, 2) the Drosophila heart model, and 3) computational model of human atria. As proof of concept, we screened 20 AF-associated genes and identified Phospholamban loss of function as a top conserved hit that shortens action potential duration and increases the incidence arrhythmia phenotypes upon stress. Mechanistically, our study reveals that Phospholamban regulates rhythm homeostasis by functionally interacting with L-type calcium channels and NCX. In summary, our study illustrates how a multi-model system approach paves the way for the discovery and molecular delineation of gene regulatory networks controlling atrial rhythm with application to AF.
