Even with the best immunosuppressive medications, transplanted organs are prone to fibrosis, or scarring, says surgery researcher Dan Warren. “Repetitive or persistent injury leads to fibrosis. For example, if you were to cut your skin in the same place over and over, you would eventually develop a scar,” Warren says.
The same thing happens to internal organs that get chronically injured through diseases such as hepatitis C. While patients who receive organs take medications to prevent rejection, the immune system still can react to the foreign organ, causing little injuries that eventually lead to fibrosis. So fibrosis both causes the need for transplant and can cause a transplanted organ to fail more quickly than it otherwise would, Warren says.
His research, supported by former patient Janet Bauer Hartman and her husband and kidney donor, Andy, aims to learn more about fibrosis and determine methods to halt it. “We’re very interested in understanding what cells contribute to fibrosis, and more specifically, what genes get turned on and off in those cells that cause them to go from their normal state to a diseased one.”
Over the past few years, his team has identified a microRNA—a short segment of RNA that binds to other RNAs to prevent them from making proteins—that may be involved in the fibrotic process.
“In basically any fibrotic organ you examine, there is a less than normal amount of this microRNA, called miR-29,” Warren says, “and we’ve shown that when you restore miR-29 back to normal levels, you rescue that organ from fibrosis.”
In work Warren and his colleagues published in 2015 in PLOS One, supplemental miR-29a improved liver fibrosis in laboratory mice. Additional papers looking at genes affected by miR-29 are planned for publication next spring, he says.
“If we can understand what genes are being regulated by miR-29, we might be able to find more traditional small molecule drugs that could be synthesized into pill form to become effective treatments for fibrosis,” Warren says. This would prolong patients’ need for transplantation and also prolong the survival of organs that do get transplanted, he notes.
Fibrosis research supported by the Hartmans, both personally and through the Charles T. Bauer Foundation, also led to a larger collaborative R01 grant from the National Institutes of Health to study the genetics of fibrosis in scleroderma, with Hal Dietz of Johns Hopkins’ Institute of Genetic Medicine. While the transplant community had long been aware of fibrosis, Warren says, the research never would have come about without the Hartmans’ support: “The impact from their philanthropy has been both broad and powerful.”
For the Hartmans, whose transplant occurred in 2001, progress like this is rewarding to see. “It’s been our privilege to be involved in something that’s proved so successful and so uplifting for the medical community,” says Janet.
Over the years, they have not only financed research efforts in transplant medicine but also established a travel fund that potential organ donors can tap into to help cover hotel and airline ticket costs while visiting Johns Hopkins facilities.