Research
We are interested in understanding the mechanisms of oncogenic transformation in relation to alterations in fundamental transcriptional networks, focusing on the function of the Myc and E2F transcription factor families which are misregulated or overexpressed in a large fraction of human cancers. My laboratory was among the first to describe the chromosomal translocation between c-myc and the immunoglobulin locus in 1982 and we have studied various aspects of Myc function ever since. The oncogenic activity of these transcription factors depends on protein domains associated with transcriptional activation, which provides an avenue to study both cancer biology and the mechanisms of gene regulation. A major contribution of my lab was the discovery of the link between Myc and E2F and the TRRAP-containing histone acetyltransferase complexes, which is currently the dominant model for the mechanism of Myc transactivation. Our studies of Myc cofactors continue, but we have also discovered another fundamental mechanism involving an unexpected aspect of gene regulation, mRNA cap methylation. A second general area of interest is the characterization of distal regulatory elements for c-myc and other critical genes involved in growth control, some of which are linked to inherited cancer risk.