To establish the next generation of physiologically relevant human cardioid models, we combine principles of in vivo organ development with bioengineering and the derivation and differentiation of organoids. Our lab's mission is to holistically understand the processes of cardiac development and disease across biological scales from the subcellular to the organoid level, combining state-of-the-art imaging (electron, confocal, light sheet, two-photon microscopy), multi-omics (single cell/spatial transcriptomics/proteomics, phospho-proteomics, ATACseq, metabolomics), and whole organoid level analysis (morphometry, Ca2+ transients, voltage, contraction). To integrate our findings and generate new predictions and hypotheses, we aim to use multimodal deep learning and new systems analysis frameworks.

The adult heart has little capacity to regenerate after injury, such as a heart attack, forming scar tissue instead of new cardiac muscle. In contrast, the growing fetal heart can repair itself. To better understand fetal growth and regeneration, the Mendjan lab is advancing cardioid models to include immune cells, epicardium, fibroblasts, and other key components to recreate cardiac growth and repair in the lab for the first time. Using this model, the team will investigate the molecular mechanisms guiding fetal cardiac proliferation and regeneration and inform new potential therapies to enhance recovery after a heart attack.

The human heart begins to form during the first days of development and starts beating as early as day twenty-three. From that moment on, it faces a remarkable challenge: continuously pumping blood while billions of new cardiomyocytes are produced and seamlessly integrated into the contracting heart muscle. By investigating how heart function and growth are coordinated, the Mendjan lab aims to reveal the mechanisms that allow the fetal heart to expand and strengthen without interrupting its essential, life-sustaining beat.