Assistant Professor, Department of Radiation Oncology,Duke University Medical Center

The major interest in our lab is to understand the transcriptional regulatory events that are critical for cancer formation. We have focused our study on a novel class of transcription factors -p300 and CBP (CREB binding protein). p300/CBP have histone acetyltransferase activity (HAT) and they function, at least in part, by interacting with and modulating multiple DNA binding transcription factors' activity. p300 and CBP both serve as cellular targets of the potent viral oncoprotein E1A. Complex formation of E1A-p300/CBP and E1A-pRb (retinoblastoma tumor supressor) are the obligatory steps for E1A mediated cellular transformation. Therefore, p300/CBP are implicated as the key components in the cellular growth control pathways. Our lab is interested in dissecting outhow E1A-p300/CBP complex formation leads to oncogenic transformation and what are the roles of p300/CBP ingrowth regulation.

We have approached these issues with a combination of genetic, biochemical and molecular approach. On the genetic front, we have generated knock-out mice deficient for p300 or CBP and started to analyze their phenotype specifically in the areas of growth and differentiaiton control. For example, we have found that some CBP +/- mutant mice are susceptible to leukemia and they also develop dramatic mammary gland hyperplasia. Dissecting out the signal events that lead to these deregulated growth control pathways will be one of our main focuses. In conjunction with the mouse model, we have also initiated a study on a Drosophila CBP mutant, hoping to use classic genetic approach to dissect out signaling components that are important for CBP's function.

On the biochemical and molecular front, we are trying to identify the critical targets of E1A-p300/CBP complex that may contribute to the transformation. We are also very interested in the regulatory mechanism of p300 and CBP, particularly on the regulation of HAT activity. The current emphasis is to identify the specific post-translational modification on p300/CBP and factors that may modulate the HAT. We are also designing experiments to identify additional substrates that are acetylated by p300 and CBP and to test the functional importance of this activity both biochemically and genetically. We hope that with a comprehensive approach as described above, we will eventually gain more insight on teh oncogenic transformation process and the function of p300 and CBP.

Phone: (919) 684-5224 – E-mail: Not Available