Research Projects

Cell differentiation and identity maintenance are influenced by gene expression programs, but the transcription dynamics of key regulatory factors crucial to B and T cell development remain unclear. Reverse genetic studies show that transcription factors PU.1, Ikaros, and E2A function at the top of the hierarchy to induce lymphoid lineage developmental competence within MPPs. Loss of expression of these factors results in a complete block to B and T lymphoid cell development. E2A, in particular, functions in coordination with Ebf1 and Bcl11b to promote B fate specification and T cell specification. Recent studies indicate that E2A is concomitantly induced in activated B cells and highly upregulated during the development of CD4+ vs CD8+ T cells. The real-time dynamics of transcription of E2A may be regulated by the quantitative threshold of exogenous signals, which may alter transcription "bursting" and mRNA decay rates. The current application focuses on establishing the transcription properties of E2A during the development and function of B and T lineage cells. A multi-disciplinary approach integrating molecular genetics, single live-cell time-lapse imaging, and computational methods is used to enhance our understanding of stochastic processes of E2A transcription. The studies are expected to provide two important insights: revealing fundamental kinetic features of E2A transcription in real-time at a single cell level during B and T cell developmental transitions and understanding the biochemical mechanisms that lead to the variability of transcript abundance driving diverse cellular processes.