Cardiovascular Development · Stem Cells · Metabolism
My research is focused on understanding how the heart is formed during mammalian development and how the congenital heart disease develops. We use mouse models and human ES/iPS cells to tackle several key questions.
- Cardio-hemo-vascular lineage analysis: We are among the first groups who uncovered the multipotency of cardiovascular progenitors (Cell, 2006), which is currently a widely accepted concept in the field. This lead to the discovery of ‘hemogenic endocardium’ (Nat Comm, 2013). We further extended this project and discovered an ‘endocardially-derived subset of cardiac tissue macrophages’ (JMCC, 2015, Dev Cell, 2019). This work suggests that aberrant macrophage function underlies congenital valvular heart disease.
- Non-genetic factors: Metabolic environments is a critical regulator of cardiogenesis. Maternal hyperglycemia is the most common medical condition that is associated with congenital heart disease. We discovered that high glucose impairs the cardiomyocyte maturation by overflowing the pentose phosphate pathway (eLife, 2017). This knowledge is being applied to the intervention to the congenital heart disease and heart regeneration. Another key non-genetic cue for cardiogenesis is the biophysical environment. We study how biophysical cues are sensed by atrial and ventricular cardiomyocytes (STAM, 2013, Circ Res, 2014).