In development, heterogeneity helps give rise to the diverse cell types in the body. Stem and precursor cells routinely differentiate into many different progeny cell types. Our hypothesis is that this feature of development may be co-opted by cancer to resist therapy. Gene expression variability has previously been attributed to “noise,” or random "stochastic" variation. Yet, the amount of variation itself is reproducible for each gene. We wish to understand what gives rise to reproducible variation at the single cell level. Our current focus is on studying enhancers, non-coding RNAs, and transcription factors. We want to understand how regulatory circuits are wired together to give rise to heterogeneity.
