Beyond editing: "Genome architecting"
Most approaches to stem-cell differentiation rely on growth factors to guide pluripotent stem cells toward specific lineages. These methods can produce cardiomyocytes, but the resulting cells are often immature, and the process is slow, expensive, and difficult to reproduce. Our lab takes a different route — genetic programming — to drive differentiation faster, at lower cost, and with greater precision. To design these programs, we first need to understand how differentiation works at the molecular level. We study congenital heart defects as “natural experiments,” where developmental errors reveal the genes and pathways that determine cell identity. This research has already uncovered key transcription factors and epigenetic regulators of cardiac fate. Yet most of these studies view chromatin only in two dimensions, along the linear genome. To truly capture developmental precision, we explore chromatin as a three-dimensional architecture.
Genome architecting integrates this knowledge through four connected steps:
- Reading – decoding how genetic perturbations influence stem-cell differentiation.
- Interpreting – mapping these effects through the lens of 3D genome organization to identify the molecular “architects” that shape chromatin folding.
- Writing – designing genetic circuits that use these factors to control cell fate.
- Scaling – implementing these programs to generate mature muscle cells reproducibly and at scale, paving the way to heal the heart and feed the planet.
Reading
Interpreting
Writing