Each year, surgeons in the University of Minnesota’s Center for Lung Science and Health (CLSH) perform 20 to 50 lung transplants on patients who have pulmonary fibrosis, cystic fibrosis, or chronic obstructive pulmonary disease (COPD)—all devastating illnesses for which transplants are often the only option.
On average, 65 percent of transplant patients live for more than five years after transplant, but a significant proportion of patients experience transplant failure. “One of the problems with lung transplants is rejection. The body is fighting a foreign object,” says Chris Wendt, M.D.,professor of medicine in the University’s Pulmonary, Allergy, and Critical Care Division. “Our goal is to prevent rejection or reverse it before the lung is irreversibly damaged.”
Wendt and Marshall Hertz, M.D., also a professor and CLSH director, were recently awarded two new grants supporting their work to improve long-term transplant survival rates and reduce incidents of transplant failure.
Wendt received a $1.7 million grant for four years from the National Institutes of Health for a project analyzing certain proteins that may indicate lung transplant rejection. In collaboration with the University’s Center for Mass Spectrometry and Proteomics, Wendt is identifying biomarkers of chronic rejection. Thus far, Wendt and colleagues have identified two indicators of chronic rejection: small proteins called defensins that the body deploys to fight infection; and Clara cell secretory proteins, which are produced in people’s airways.
A change in these proteins is predictive of rejection two to five years after transplant, says Wendt, who already is testing the role of Clara cell protein in mice. She hopes this proteomic technique can be used to study other lung diseases as well.
In another project, Hertz is researching how gene expression can be connected to improvements in the long-term survival of transplant patients. He received a two-year $918,000 grant from the American Recovery and Reinvestment Act to advance research he began in 2002. Using cells from the lungs of transplant patients, Hertz looks for gene markers that indicate the potential for lung failure. That information could allow doctors to intervene before irreversible damage occurs to transplanted lungs.
Hertz says that he has identified groups of genes associated with transplant rejection, and is currently doing additional studies to confirm and expand his findings.
Both Wendt and Hertz hope their projects help lead to the prevention and early diagnosis of transplant failure and to the development of less invasive, therapeutic interventions for transplant patients. “Our hope is that some day we will have non-invasive tests to detect chronic rejection early in its course, allowing us to intervene and prolong organ and patient survival.”
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