Written by Whitney L.J. Howell

Medicine and science are constantly on the lookout for ways to make a better drug – a more finely-tuned medication that can attack a disease in a more pin-pointed fashion.

Donald McDonnell Ph.D., a Duke University professor of medicine, has played a significant role in this push, commonly known as personalized medicine, for more than a decade. His research with nuclear receptors – proteins that sense steroid and thyroid hormones and contribute to regulating gene expression – has affected change in multiple pharmaceutical companies worldwide. In fact, these nuclear receptors are involved in more than 20 percent of all written prescriptions.

By focusing on the more than 40 nuclear receptors involved in breast and prostate cancer, McDonnell’s lab has made a substantial impact in pharmaceutical research and drug design.

“I believe we have significantly influenced the way drug target receptors are developed,” he said. “I think we have improved drug discovery programs in many companies, but I believe the approaches and technologies we’ve developed have informed programs in many – if not all – companies in this area.”

Initially, McDonnell launched two companies around his research, but he ultimately decided to make his findings freely available to organizations working on highly-specific medications.

The cancers McDonnell’s team have tackled involve receptors that turn on in the presence of estrogen, progesterone, and androgen. Their goal is to understand how the receptor-hormone connection works in order to successfully interrupt it through tailored medications that can make treating disease more effective. Recently, they discovered a particular nuclear receptor, estrogen related receptor-alpha, that must be present for breast cancer cells to grow and spread, making it a high-priority target for his group.

In addition, McDonnell’s team discovered the mechanism behind resistance to Tamoxifen, the primary intervention used in the 70 percent of breast cancer cases that are ER (estrogen receptor) positive, and developed a screening technology for drugs that can circumvent that resistance. At least two alternative drugs are now used clinically, he said, because of the screening capability.

“The goal of translating research in an academic setting is not financial, but to translate discoveries and make them into something useful for the patients,” he said. “It’s an obligation we have. First and foremost. There’s simply no point of doing research if it can’t be translated.”

In that vein, McDonnell is collaborating with other investigators to translate research around nuclear receptors involved in acute macular degeneration and prostate cancer into effective medications. Work has already begun, he said, to establish a prostate cancer treatment company around seven series of drugs his team developed. They’re currently pursuing a Phase 1 clinical trial.

Duke was intricately involved in McDonnell’s entrepreneurial success. Not only did university administrators connect him with individuals both within and outside the institution who were equally interested in translating research into practical use, but Duke also offered him the incubator space needed to test possible links between targets and medications.

“There is a big interest in translational research here at Duke,” he said. “There are so many initiatives and people involved. The University has been very proactive in enabling this type of work.”

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