Research Interests
The focus of our laboratory is the study of protein-DNA interactions involved with the regulation of gene transcription and DNA repair of genes in normal and cancerous human cells. More specifically, we investigate the molecular mode of action of the HMGA group of non-histone chromatin proteins. The HMGA proteins play a vital role in cell metabolism and have been referred to as the "hubs of nuclear function" because of their involvement in such diverse processes as gene transcription, DNA replication, DNA repair, senescence, apoptosis and integration of retroviruses (such as HIV) into the genome. Furthermore, the HMGA proteins ‘shuttle’ between the nucleus and the mitochondria in a cell cycle dependent manner in normal cells but in a disregulated manner in cancerous cells. Within mitochondria HMGA binds to the D-loop control region of mitochondrial DNA and influences both mitochondrial replication and function thus providing the first example of a nuclear chromatin protein that also participates in regulating the function of a cytoplasmic organelle. And, finally, we and others have also recently demonstrated that the HMGA proteins are causally involved in both the cancerous transformation of normal cells and in the promotion of tumor cells to more malignant states, thus making them attractive targets for new anti-cancer drugs.
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