Dr. Bert O’Malley, professor of molecular and cell biology, has focused his research on the molecular mechanisms that guide gene regulation in endocrinology and endocrine cancers. His work has improved our understanding of the molecular mechanisms by which hormones, receptors and coactivators contribute to the disease process. His pioneering work in this field has shown that intracellular hormones and cofactors act at the level of DNA to regulate the production of proteins and affect the function of the cell. Recent research reported in Molecular Cell was the first to solve the structure of a functional receptor-coactivator complex on DNA capable of regulating gene transcription in vitro. In addition, in a paper published in the Journal of Clinical Investigation, he showed that steroid receptor coactivator-2 (SRC-2), which is highly elevated in a variety of tumors, is likely implicated in metabolic coordination of cancer metastasis, opening the possibility of therapeutically targeting the SRC-2 pathway.
His work with steroid receptor coactivator-3 (SRC-3), a prognostic marker for aggressive human breast cancer, showed that small-molecule inhibitors that directly bind SRC-3 cause selective degradation of the complex, hereby killing cancer cells with no observable toxicity. Small-molecule inhibitors represent a new type of oncologic drugs that target coactivators.