Anne-Karina Perl, PhD

American Lung Association Scholar: The Immune System, Inflammation and Lung Scarring

Anne-Karina Perl, PhD, is investigating how airways regenerate after acute and chronic injury and what causes airway wall thickening, which leads to airway obstruction in COPD. Airway injury and wall thickening also occurs in bronchiolitis obliterans syndrome (BOS), which is the main chronic complication after lung transplantation. Understanding the cause of airway wall thickening may lead to improved treatments for both conditions.

"Despite the importance of COPD as a disease, the mechanisms underlying it are still very poorly understood," says Dr. Perl. "We want to understand how airway wall thickening is activated and how we can interfere with it."

With help from an American Lung Association Biomedical Research Grant, Dr. Perl is studying a mouse model of acute and chronic injury of the cells lining the airways, which can lead to airway wall thickening. She is looking at regeneration of the cells after airway injury. Her hypothesis is that epithelial growth factor receptor (EGFR), a substance that is present in the membrane of the lung cells, plays a beneficial role after short-term, or acute injury but has a detrimental role after long-term, or chronic lung injury. In acute lung injury, EGFR sends signals needed for repair of airway cells. But in chronic lung injury, EGFR signaling leads to fibrosis, or scarring of the lungs. "We think that the right balance of EGFR activation is needed to regenerate the lung after acute lung injury, but has a detrimental effect after chronic injury and leads to fibrosis or the airways." Dr. Perl said.

She plans to test whether a drug called gefitinib (Iressa), used in some countries to treat non-small cell lung cancer, suppresses fibrosis in the lung. Gefitinib targets and blocks an enzyme called tyrosine kinase, part of EGFR signaling.

"I hope the findings from the research I perform with the American Lung Association grant will provide the groundwork for more extensive funding on a national level," Dr. Perl said.