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May 29, 2013

四色AV toxicology professor invited to contribute to "Science Signaling"

Dr. Sharon Meyer, 四色AV Associate Professor of Toxicology, was invited by the editors of "Science Signaling" to contribute a Perspective.

Perspectives accompany highlighted research articles and emphasize the research's novel aspects such as the authors' viewpoint, innovative application of methods, and policy implications.

Her Perspective will promote the magazine's recent publication of a research paper describing a major advance in the field of drug metabolism.

The highlighted research paper, "Phenobarbital Indirectly Activates the Constitutive Active Androstane Receptor (CAR) by Inhibition of Epidermal Growth Factor Receptor Signaling," comes from the laboratory of Masahiko Negishi of the National Institute of Environmental Health Science (NIEHS) of the National Institute of Health (NIH).

Negishi's research team has produced decades of high quality research on drug metabolism.

A key finding in the new paper was that phenobarbital, an anticonvulsant with over 100 years of use and a classical activator of expression of metabolic enzyme genes of the cytochrome P450 2B family in liver, does so indirectly by binding to and inhibiting activity of a signaling molecule of the cell's surface, the EGF receptor.

This target was unexpected because EGF receptor function is more commonly associated with regulation of cell growth.

"This was truly a pi猫ce de r茅sistance," said Meyer, "succeeding after a 50-year quest by many other researchers for a pharmacological phenobarbital receptor."

The editors approached Meyer based on a link to her expertise in work she conducted twenty years ago while a Research Assistant Professor at Duke University Medical School.

With colleague Dr. Randy L. Jirtle, Meyer discovered that phenobarbital, a promoter of liver tumors in rats, directly suppressed growth of rat liver cells by EGF through inactivation of its receptor.

This finding was supportive of one model for the process of cancer formation, in which chemicals that accelerated growth of cancer precursor cells also inhibit growth of noncancerous cells, thus creating an environment where tumor cells have a selective advantage.

"It is gratifying to be invited to support this new, exciting work of Negishi with a Perspective," said Meyer.

"One of the greatest challenges in a research career is maintenance of sustainability and pedigree recognized by peers over the years. To be approached because of our earlier research, now providing a broader context for the new finding through linkage to another important cellular function, is exciting for the field of cellular signaling and very rewarding personally."

"Science Signaling" is a specialty journal of "Science," a widely read resource for scientific discovery that is published by the American Association for the Advancement of Science.

The research article from the Negishi group and Meyer's Perspective are published in the May 7 issue available at:

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