My Work
Ninety-eight percent of our DNA is the same as a chimpanzee. But the difference—why we humans all have individual looks—involves gene regulation—something of which we know very little.
We know much about proteins and how they are coded, but we don’t know how they are expressed in a disease or in a normal state. That's the basis of gene regulation. Basically, my focus is on trying to interpret the rest of the human genome.
The chromatin in which the genome is wrapped changes as a cell develops. Basically, the transcription factors involved in regulation don't read the whole genome—they only read the parts of the genome that are accessible, which is a very small percentage.
One of my projects is to take what we've learned from yeast and start applying it to a developing system. We are studying developing cells in different stages and how the chromatin landscape is rearranged in each of those stages, and how those rearrangements correspond to the phenotype of that cell.
The same model can then be applied to cancer development, beginning with a pre-cancerous cell. There are chromatin changes that have to take place in order for that cell to become cancerous. It's the same idea as studying the developing system with the same mechanisms involved.
My Research
Transcription factors are directed to their genomic targets by DNA sequence, local chromatin structure, and protein-protein interactions. These modulators of transcription factor binding are not independent but function both cooperatively and competitively to regulate where transcription factors bind. Understanding how these modulators affect transcription factor binding in vivo remains a major unsolved biological problem.
My laboratory integrates both experimental and computational approaches to:
- investigate transcription factor binding in response to environmental stress,
- identify and characterize the mechanisms directing transcription factor target selection,
- determine how developmental signals reshape the epigenetic landscape during mouse development, and
- develop bioinformatics tools to analyze and interpret ChIP-chip experiments.