Current Research and Scholarly Interests
Since participating in the initial identification of the protein product of the v-Myb oncogene as a postdoctoral fellow, I have dedicated my research career to understanding the function of the highly conserved Myb oncogene family. We initially focused on the retroviral v-Myb oncogene and its cellular homologue, c-Myb. More recently we have focused on the fruit fly Drosophila melanogaster as a model organism for understanding the human Myb oncogene family. We created the first null mutants of the sole Drosophila Myb gene, and showed that the absence of Myb resulted in mitotic abnormalities including chromosome condensation defects, aneuploidy, polyploidy, and aberrant spindle formation. In collaboration with the laboratory of Michael Botchan (UC Berkeley), we also showed that Myb was required for the site-specific initiation of DNA replication that occurs during chorion gene amplification in adult ovarian follicle cells. We ourselves then showed that the absence of Myb causes a failure in the normal progression of chromosome condensation from heterchromatin to euchromatin. Most recently, we have found that Myb acts in opposition to repressive E2F and RB proteins to epigenetically regulate the expression of key components of the spindle assembly checkpoint and spindle pole regulatory pathways.
To investigate the functional evolution of the three Myb genes present in all vertebrate species, we tested which if any of these vertebrate Myb genes could complement a Drosophila Myb null mutant. We found that B-Myb, but neither A-Myb nor C-Myb, could complement the defects in proliferation and differentiation seen in Myb null Drosophila hemocytes. These results argue strongly that Drosophila Myb is in fact the orthologue of vertebrate B-Myb. Therefore, studies of Drosophila Myb are likely to be highly informative about the function of vertebrate B-Myb. Importantly, elevated levels of B-Myb expression are a clinically significant predictor of poor prognosis in human breast cancer and other malignancies.