Researcher Profile: Richard A. Pierce, PhD

Excerpted from the 2000 Barnes-Jewish Hospital Research Annual Report. Reprinted with permission.

Until children reach the age of 4, their bodies have a remarkable capability: the elastin fibers in their lungs can regenerate to repair damage. This ability continues at lower levels throughout childhood and adolescence, but by the time people reach adulthood, it is lost. For this reason, the only treatment options for progressive diseases like emphysema are those that slow the disease process, not reverse it.

Until recently, most research dealing with lung damage focused on lessening the damage or preventing it from occurring. Four years ago, Richard Pierce, PhD, began working to identify strategies to improve the lungs’ ability to repair damage and restore function.

“We think that when the mechanisms of growth are active, even at a low level, the genes responsible for repairing the lungs’ elastin fibers are easier to reactivate. But reactivating them once they are shut down completely in full-grown adults seems to be much harder,” says Dr. Pierce. “When adults’ lungs are damaged, a sloppy repair job results – it’s like a contractor with no experience arrives and just begins hammering nails in, rather than working on a careful reconstruction.”

The Human Genome Project, which has identified all the genes on the human DNA, is helping speed Dr. Pierce’s research. Using a new technology called gene arrays or DNA chips, he and his colleagues are able to examine up to 20,000 to 30,000 genes and catalog their level of gene expression – what they look like and what they do – under different conditions.

“Now we can look at a lung that’s regenerating, characterize its gene expressions, and then compare those findings to what is happening in a lung that is not regenerating,” explains Dr. Pierce. “At that point, the task is to try to make intelligent guesses about which are the critical genes involved in repairing elastin fiber.”

Within two years, Dr. Pierce hopes to identify the signaling pathway critical to lung regeneration. The next step would be working with pharmaceutical companies to develop drugs that activate the pathway and test their viability.

“A key part of lung regeneration is to repair and restore the organ’s fine architecture,” he says. “In many other tissues, this is not important, but the lung undergoes constant deformation – constant expansion and return to normal size. Any structural abnormality makes it hard to breathe, so our goal is to make sure damaged lungs are able to regain their full function.”