My research has involved applying chemical and genomic tools to study two kinases that play a role in transcriptional initiation, the initial step of gene expression. In collaboration with K. Shokat (UCSF), we have designed two altered yeast cyclin dependent kinases, Srb10 and Kin28, that bind an ATP analog with high specificity and affinity. The ATP analog can traverse the cell membrane quickly and inhibit the function of the targeted kinase in iving yeast cells. I will explore the effects of inhibiting kinases on the expression of genes on a whole genome basis.
In collaboration with P. Dervan (CalTech), we are designing distamycin/netropsin like small molecules, polyamides, that can target specific DNA sequences. We are utilizing various chemical alterations to uniquely target specific sites in the yeast genome, and will use genome-wide location analysis to rapidly characterize specific binding sites for a given polyamide in the genome (since there may be up to 50,000 potential ones).
I am also interested in studying clinically relevant problems (such as the onset of specific cancers) using genomic tools including genome wide expression profiles.