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November 2, 2009
Pathologist takes a chance in science and art

By Quinn Eastman

David Lambeth’s scientific career is a reminder of Pasteur’s adage that chance favors the prepared mind. While exploring the origin of free radicals and reactive oxygen in cells, his laboratory discovered the existence of a new family of enzymes that produce them. Starting in the late 1990s his lab linked the enzymes to human cancer and — along with cardiology researcher Kathy Griendling, also at Emory — to heart disease.

Since then, these enzymes, called NADPH oxidases or Nox enzymes for short, have rapidly become a field of inquiry unto themselves. Scientists around the world have identified NADPH oxidases as important for basic processes across many species. They help plants fight off pathogens, guide sexual development in fungi, are essential for egg laying in flies and even help humans to sense gravity.

The professor of pathology and laboratory medicine’s first exposure to the study of reactive oxygen began at Duke, where he attended graduate school in biochemistry. Lambeth worked with Henry Kamin on enzymes that use oxygen to modify hormones, and next door was Irwin Fridovich, who had identified an enzyme called superoxide dismutase that “mops up” reactive oxygen.

Scientists have known about forms of reactive oxygen for several decades, but for much of that time they were thought to be only short-lived “sparks” thrown off by mitochondria, cells’ miniature power plants.
That picture changed slightly when certain immune cells were found to make bursts of reactive oxygen to kill bacteria. During the 1990s, Lambeth was studying the enzyme immune cells used to make these bursts.
He became intrigued when clues appeared that cells outside the immune system, such as cells lining blood vessels, also made reactive oxygen. “If we had trusted the assumption that the reactive oxygen was coming from mitochondria, we would have never gone looking for the Nox enzymes,” he says. “What started as a side project quickly became our major focus.”

Lambeth says it’s an accident that scientists discovered a reactive oxygen producing enzyme in immune cells first. Because Nox enzymes are so widespread throughout the evolutionary tree, it’s probable that their functions in cell signaling came long before their role in fighting bacteria.

Now the Nox field is heading in “many directions at once,” Lambeth says. Some researchers are reaching back to find the fundamental roles they play in cell signaling while others are looking ahead to applications in fighting disease.

Lambeth himself teamed up in 2006 with scientists from Geneva, Kyoto and his home state of Texas to found a Swiss-based company, GenKyoTex. GenKyoTex is developing inhibitors of NADPH oxidases as potential treatments for diseases such as pulmonary fibrosis, diabetic neuropathy and hypertension.

Like his science, Lambeth’s artistic pursuits also reflect a combination of serendipity and strategy. He is an enthusiast for acoustic fingerstyle guitar playing — think Richard Thompson and shimmering arpeggios.
At times, Lambeth has joined up with other musicians to form various bands. One iteration had him teamed up with a graduate student who plays Irish fiddle.

“The problem for me with playing in a group is that eventually some of the musicians want to become famous or at least play for money,” he chuckles. “I had those same delusions in college, but at this point, I just want to play for myself and my friends, usually in someone’s living room.”

In addition to guitar playing, Lambeth has been stretching his creative side as a painter. He says he’s mostly self-taught, augmented by a few courses at Callanwolde Fine Arts Center.

“For me, it’s another form of experimentation, with colors and solvents instead of cells and enzymes,” he says.

He had enjoyed painting as a teenager, and started painting again as his 40th birthday approached. He says he started out more in the style of the Impressionist school, depicting for example dappled reflections on water.

Recently, he has grown more classical, while still retaining the pure, bright colors used by the Impressionists. A painting in his office shows the owner and sole employee of a three-table restaurant he met on a remote beach near Zihuatanejo, Mexico.

“I tried to emphasize the folds of her dress and the pride that showed through on her weathered face and resolute posture,” Lambeth says.