Research

Every single cell in an organism has almost the exact same genomic information, yet cells in the body develop into vastly different cell identities. How does one cell become a liver cell and another cell become a skin cell? This terminal differentiation into distinct cell types is due to the turning on of some genes and the turning off of other genes–a phenomenon known as transcriptional regulation. My lab investigates this transcriptional regulation integrating genomics and computational biology with classical genetics in C. elegans, studying the conserved transcription factor NHR-25.

How do transcription factors coordinate cell-type specific transcription?

The turning on or off of correct genes by TFs is critical to specifying the correct cell type. Yet even the simple question of determining which gene a transcription factor regulates is not straightforward, since transcription factors bind to sites in the DNA that are distant from the promoters they act on. We are investigating the transcriptional regulatory network of NHR-25 through high-throughput sequencing and genome-editing methodologies to correlate transcription factor binding with the target gene it regulates at various larval stages and in distinct tissues.

What factors restrict TF action to its target gene?

Often a bound transcription factor is in equal proximity to both its target gene and genes the TF does not regulate. How are these other genes shielded from the action of the nearby transcription factor? Through genetic screening and computational approaches we are investigating how transcription factors specifically act on their target genes and not other promoters nearby in the nucleus.