Lei Bu, PhD
Heart regeneration and disease modeling
cardiovascular progenitor cells, disease modeling, pluripotent stem cells, genome editing
Over the past few decades, studies in mouse models have revealed many of transcript factors critical for normal mammalian cardiovascular development, including Isl1, Nkx2-5 etc. However, in contrast to murine cardiogenesis, human heart development requires the generation of a more complex structure and a longer period of heart cell lineage diversification and expansion, suggesting the possibility of divergent cell sources and pathways. Due to the inadequacy of in vivo genetic tools, the precise mechanisms of human cardiogenesis remain poorly understood, which will be crucial for understanding the pathogenesis of congenital as well as adult-onset heart disease. We are interested in the basic biology of human cardiovascular progenitor cell specification, migration, differentiation, and potentials for heart regeneration. We primarily work with the human stem cells with collaborators in human and mouse genetics, and include large animal models to explore cardiac progenitor formation, expansion and lineage diversification.
Heart failure affects four million people in the US alone and is associated with high morbidity and mortality. Like other multifactorial conditions, its progression is modified by the genetic diversity of the affected individuals. We are interested in using the latest technology in stem cells with engineered nucleases to develop “disease in a dish” models. We hope to establish platforms for studies of pathological mechanisms of heart failure, discovery of new agents to treat heart disease, and derivation of transplantable adult-like cardiac resident stem cells from pluripotent stem cells or effective strategies for mobilizing resident stem cells.