Current Research and Scholarly Interests
Cancer is caused by mutations in oncogenes and tumor suppressor genes. Mutations are changes in the DNA sequence that may alter gene function. Gain-of-function mutations can activate oncogenes, whereas loss-of-function mutations can inactivate tumor suppressor genes. Our laboratory studies the Myb oncogene family that is mutated in human cancers of blood cells (leukemia), brain, breast, and salivary gland. The proteins encoded by Myb genes bind to DNA and regulate the expression of other genes that control cell division, differentiation, and cell death. The Myb proteins interact with a highly conserved multi-protein complex called the MuvB core. The same complex also interacts with proteins of the Rb tumor suppressor family and the E2F transcription factor family. Work from our laboratory has shown that Myb acts in opposition to Rb-E2F to epigenetically regulate gene expression. In addition to vertebrate animals and retroviruses, we used Drosophila melanogaster (fruit fly) as a model system because of the powerful genetic, genomic, and cell biological tools available in this organism. We also showed that although C. elegans (nematode worm) lost its animal-type Myb gene hundreds of millions of years ago, the Drosophila Myb “key” still binds to and can open the highly conserved worm MuvB “lock” that represses gene expression.
