Cardioids Reveal Self-Organizing Principles of Human Cardiogenesis
The Mendjan lab aims to recapitulate human heart development in vitro, discover the molecular mechanisms driving cardiac self-organization, and how this fails in congenital heart disease. We use human pluripotent stem cell differentiation into self-organizing heart organoids called "cardioids" (Hofbauer et al., 2021) to decipher the molecular control of cardiac organogenesis and associated disorders. Our guiding principle is that to fully understand heart development and disease in patients, we must recreate these linked processes in the lab. We hypothesize that organoids need to recapitulate development as faithfully as possible to serve as predictive disease models. Missing human cardiac models that allow the development of therapies and predict responses in patients are the most significant bottlenecks towards much-needed treatments in cardiovascular disease. Our mission is to address this key problem causing more deaths than any other disease globally. To achieve our objectives, we systematically apply principles of in vivo development and translate them to in vitro models. This approach allows us to dissect organogenesis from the tissue scale to the cellular, molecular, and structural levels. Our lab benefits from my Ph.D. and postdoc experience across these biological scales, illuminating fundamental biochemical mechanisms of transcriptional regulation (Mendjan et al., 2006) and how signaling controls the transcription factor, epigenetic and mRNA machinery directing cell specification (Mendjan et al., 2014; Bertero et al., 2015; 2018). We combine organoid model development (Hofbauer et al., 2021; Haider et al., 2018; 2019) with electrophysiological, genomics, proteomics and EM ultra-structural methods to elucidate the mechanisms of organogenesis, cardiac multi-chamber morphogenesis, growth and regeneration in vitro. By doing science, we learn how to efficiently teach, work in a team, communicate, present and apply the scientific method to the highest standard. As a lab head and teacher, I am committed to my students through dedicated supervision, mentoring, and an organizational framework that promotes asking critical questions and having fun while learning and making discoveries.