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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.
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