Donald Patrick McDonnell
Chair, Department of Pharmacology & Cancer Biology

The nuclear receptor superfamily of ligand-regulated transcription factors are the targets of drugs that account for over 20% of all prescriptions written. Within this family of over 40 proteins are receptors that enable cells to respond to steroid hormones, thyroid hormone, retinoids and vitamin D. Also contained in this family are several “orphan receptors” for which specific hormones remain to be identified. The research in our laboratory is focused on defining the mechanism of action of those nuclear receptors whose expression and/or activity is implicated in the pathogenesis of breast and prostate cancer. We have a specific interest in defining the signaling pathways in these cancers in which the estrogen, progesterone and androgen receptors are engaged. It is anticipated that, by targeting critical steps in the signaling pathways of these receptors, molecules with new mechanisms of action can be developed that are likely to be more effective than existing drugs of this class. Furthermore, we have recently determined that the orphan nuclear receptor, Estrogen Related Receptor-alpha (ERR alpha), is required for the growth and metastasis of breast cancer cells, making it a target of high priority for our group. Projects ongoing in the laboratory range from the most fundamental, where an understanding of the mechanism(s) by which nuclear receptors regulate gene transcription is the goal, to the very applied, where the development of novel pharmaceuticals is the desired endpoint.

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