by Janet Wagner

innie Holmes-McNary, a molecular nutritionist, has an abiding interest in how the foods we eat affect our health—both positively and negatively. With Albert S. Baldwin, Jr., professor of biology, she has determined how trans-Resveratrol (Res) controls gene expression. A phytoalexin (an antibiotic compound produced by plants to combat pathogens such as fungal infections), Res is most abundant in red grapes, muscadine grapes, and grape products such as wine.

"This is very exciting work because I believe it explains how diet modulates changes at the molecular level," Holmes-McNary says.

As a doctoral student, she studied the deleterious effects of alcohol on the breast and alcohol's role in the development of breast cancer. Intent on studying how diet affects gene expression, she joined Baldwin's lab at the Lineberger Comprehensive Cancer Center as a postdoctoral fellow. It was 1997, and the discovery by University of Illinois scientists that Res, which is also found in mulberries, raspberries, and peanuts, has anticancer and anti-inflammatory attributes flooded both scientific and popular media. The scientists contended that Res was behind what has been dubbed the French paradox.

Much has been made of the observation that the French enjoy both a high-fat cuisine and lower rates of some cancers and coronary heart disease than Americans. The Illinois researchers proved that the French custom of taking Res-rich wine with meals was protecting them from the ravages of disease. But, they didn't explain how Res worked its magic, and that missing piece to the puzzle intrigued Holmes-McNary.

"The fact that trans-Resveratrol has both anticancer and anti-inflammatory potential made it very interesting," she says. Holmes-McNary and Baldwin knew that to have those properties, Res had to be controlling gene expression. As she read the Illinois researchers' findings, Holmes-McNary conjectured that Res was working through the protein NF-kB.

NF-kB is part of a delicate chemical cascade in which the activation of one protein initiates the successive activation of other proteins. For NF-kB to be released to a cell's nucleus and function as a transcription factor (involved in proliferation and cell growth), the protein IkB kinase, which is upstream from NF-kB in the cascade, has to be activated—IkB kinase regulates NF-kB activation.

Next: the "eureka" moment

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