Epigenetic Regulation of Gene Expression and DNA Repair in Cancer Focus Group
The common thread of this group is their conviction that chromatin - with its dynamic regulation and virtually limitless epigenetic complexity - significantly impacts gene transcription and DNA repair in cancer cells, thereby promoting cellular proliferation, invasiveness and metastasis characteristic of the malignant state. In this regard, two labs (Bodily and Scott) are seeking to understand how human tumor viruses (Epstein Barr virus and papillomaviruses) induce epigenetic alterations to their own genomes as well as those of host cells. Such epigenetic modifications may regulate the expression of genes central to the viral lifecycle and ultimately, to the oncogenic state of the infected cells. Two other labs (Pruitt and Gross) are investigating the role of chromatin in the regulation of transcription, with particular focus on the Cyp19A1 gene that encodes the protein aromatase that directly contributes to the malignancy of the majority of breast cancers. This research is conducted on a eukaryotic model of HSF1-regulated genes whose counterpart in human cancers is driven by a trascriptional program distinct from heat shock to support the highly malignant state. In addition, research about the way gene activation occurs in silent heterochromatin may provide insight into strategies for reactivation of tumor suppressor genes inappropriately silenced by heterochromatin. Finally, two other labs (De Benedetti and Harrison) study the role of chromatin and epigenetic modification in regulating the repair of double-stranded DNA breaks. One lab uses a novel episomal system in mammalian cells that permits purification of minichromosomes undergoing double-strand DNA repair for detailed chemical bioanalysis. The other lab studies double-stranded DNA breaks in human mitochondrial DNA whose chromatin structure and epigenetic character are very poorly understood.