Jeffrey Koenitzer, MD, PhD

The formation of scar tissue is a normal part of the body's response to injury. However, in the lung there are diseases in which this scarring is uncontrolled and leads to replacement of normal lung with scar tissue, called pulmonary fibrosis. In severe forms this leads to death or lung transplant within a few years. A protein from the lung found circulating in blood, called LTBP2, has been recently found to predict how quickly lung disease will progress in patients with pulmonary fibrosis. This is potentially helpful for patients and their physicians, but it would be most useful if the specific role of LTBP2 in lung fibrosis was known. We will identify the relationship between LTBP2 in blood from patients with lung fibrosis taken before they received a lung transplant, and the levels and activity of LTBP2 in diseased lungs removed from those patients during the transplant. If a relationship can be shown, it may allow us to target LTBP2 as treatment in patients with elevated blood levels. Additional studies will be performed to uncover how LTBP2 impacts the development of lung scarring.

Catalyst Award, applied under the Dalsemer Award

Update: We have confirmed the overexpression of LTBP2 in human fibrosis samples and identified increased expression in other lung diseases that are more common: severe asthma and COPD. We have also shown that LTBP2 expression occurs primarily in disease-associated cells called myofibroblasts, and that these cells continue to produce excess LTBP2 when isolated from pulmonary fibrosis (PF) lungs. In a mouse model, we have learned more about LTBP2’s role in PF, including confirming that the protein is required for the development of fibrosis. We were also able to slow down migration of fibrotic fibroblasts with LTBP2-directed antibody, which suggests therapeutic potential for interference with this pathway. We are now working to understand how features of PF differ in patients with high LTBP2 levels in circulation.