$10M Grants Will Fund New Research Seeking to Improve Transplant Outcomes

A series of new research projects will seek to better understand how the immune system responds to transplanted organs, including the lungs. The goal is to find ways to increase the viability of organs after transplant, which could improve care for conditions like cystic fibrosis (CF).

The projects are being funded by a $7.7 million program grant from the National Institute of Allergy and Infectious Diseases that’s focused on lung transplant rejection, and a $2.6 million award from the National Heart, Lung, and Blood Institute, which is directed at heart transplant rejection. Both organizations are part of the National Institutes of Health (NIH).

“The ultimate goal is to improve the long-term outlook for lung and heart transplant patients,” Daniel Kreisel, MD, PhD, principal investigator of both grants and the surgical director of lung transplantation at the Washington University School of Medicine and Barnes-Jewish Hospital, said in a press release.

“Understanding how immune cells respond to transplanted organs sets the stage for developing novel therapeutic strategies to improve outcomes for transplant patients,” Kreisel added.

Lung transplant is often the only available treatment option for end-stage lung disease — which can be caused by CF and other conditions. However, there is a fairly high risk of organ failure, with only about half of transplanted lungs still functioning five years after the surgery. This is markedly lower than the five-year organ survival rates for heart, liver and kidney transplants, all of which are about 70%.

“Uncovering the basis for the poor survival of lung transplant recipients should also give us new insight into the causes of other inflammatory diseases that affect the lung,” said Andrew Gelman, PhD, professor at Washington University.

The new funding will support three different research projects: one led by Kreisel, one by Gelman, and one by Alexander S. Krupnick, MD, director of the lung transplant program at the University of Maryland. All three projects will examine different aspects of lung transplant tolerance.

At a conceptual level, the body’s immune system is designed to attack anything that is not part of the body — in turn, what is part of the body, the immune system should leave alone, or “tolerate.” The goal behind studying tolerance in the context of transplants is to find ways to ensure that the transplanted organ is tolerated by the immune system. If the immune system attacks the transplanted organ, it can lead to rejection.

“It is our hope that through our research, we will gain critical new insight into the immunological underpinnings of transplant tolerance and rejection,” Kreisel said.

In addition to lung transplants, the funding also will support research into heart transplants. Specifically, the scientists will try to better understand the role of immune cells in primary graft failure, when the transplanted heart does not work properly.

“Our research will focus on alternative approaches based on targeting immune pathways and cell populations in the donor heart. We hope that insight gained from the research will result in new therapies that will increase donor heart availability and improve survival after heart transplantation,” said Kory J. Lavine, MD, PhD, a professor at Washington University and also a principal investigator.