Ming-Hui Fan, MD

A Novel Protein May Protect Lungs Against Scarring After Injury

When Ming-Hui Fan, MD, took care of pulmonary patients during her residency, she was especially moved by those suffering from idiopathic pulmonary fibrosis (IPF). “These patients really stuck out in my memory, because we had no way of helping them,” she says. “When I decided to specialize in pulmonary medicine, IPF was a major area of interest for me.”

“These [IPF] patients really stuck out in my memory, because we had no way of helping them.”
IPF is characterized by progressive lung injury and scarring, leading eventually to death within two to four years of diagnosis on average unless the patient undergoes a lung transplant. Little is known about the cause of the disease, and no effective medical treatments exist to reverse or even to slow down its progress.

While doing her pulmonary and critical care fellowship at the University of Pennsylvania, she worked with cancer researcher Ellen Puré, PhD, whose lab had discovered that tissues of patients with IPF had increased levels of a protein called fibroblast activation protein (FAP). This protein has the ability to break down scar tissue in the lung. It is produced in the developing embryo and production is turned off shortly after birth. It is not produced in normal healthy adult tissues.

Dr. Fan found mice bred to be deficient in FAP have decreased survival and increased lung scarring. Her work demonstrates that FAP lessens the degree of pulmonary fibrosis that develops after lung injury in mice. “We don’t have a clear picture of what FAP acts on,” she says. She hopes to gain a greater understanding of this in her current research, which seeks to take what she has learned from mice into humans. To do this, she is studying lung fibroblasts (cells which produce the collagen of scar tissue) grown from the lungs of IPF patients who received transplants.

ldquo;We have shown that FAP plays a protective role in the lung, minimizing scarring after injury,” Dr. Fan notes. “Now we can consider ways to increase FAP expression, enhance enzymatic activity, and try to find out exactly what FAP is affecting in the tissue in order to boost its effect downstream.”

Her American Lung Association Dalsemer Research Grant has provided her the opportunity of having additional staff support. “I’ve been able to get extra hands to help with the work, which has been enormously helpful,” she says. “I can focus more on the big picture.”