Since the early 1990s, our laboratory has focused on gene regulation in eukaryotes. Correct regulation of transcription is critical to cell function and development, and deficiencies in this regulation can lead to abnormal development and a variety of genetic diseases, including cancer. We use yeast (Saccharomyces cerevisiae) as a model organism for most of our research. Yeast cells and those of higher eukaryotes, including ours, show strong similarity at the molecular level, and many insights into general transcriptional regulation have emerged from studies with yeast.
Our current research is focused on the Mediator complex. Mediator is a large, multi-subunit complex (25 subunits in yeast) that is conserved across the eukaryotic kingdom. Our recent studies have revealed that in yeast, Mediator is recruited to many genes by activators via subunits in its tail module, and these genes are highly enriched for TATA-containing, SAGA-regulated genes. The large majority of genes in yeast are regulated by TFIID and lack consensus TATA motifs; Mediator is evidently recruited to these genes independently of the tail module, but the mechanism by which this occurs is unknown and is a topic of investigation in our lab. We are also investigating the dynamics of Mediator association, and are beginning studies on how transcription depends on specific Mediator subunits in mammalian cells.
In addition, we are collaborating with Joan Curcio to study the role of Mediator in Ty1 retrotransposition in yeast. We use approaches that include molecular genetics, biochemistry, high throughput sequencing, and bioinformatic/computational methods.
