UCLA researchers have identified proteins that may help protect livers from damage during transplantation, potentially increasing the number of organs suitable for transplant. The study, published in JCI Insight, used a mouse model to examine how certain proteins guard against ischemia-reperfusion injury—a type of damage that occurs when blood supply is cut off and then restored during liver transplantation.
The research focused on two proteins, CEACAM1 and Human Antigen R (HuR), which act as “protective switches” to reduce inflammation and tissue damage during the transplantation process. Using RNA-based tools, the team was able to boost these protective effects in mice. They also observed a similar relationship between HuR and CEACAM1 in human livers that had been discarded as unsuitable for transplant.
Dery, an associate adjunct professor of surgery at UCLA and co-senior author of the study, explained the potential impact: “One of the most intractable problems in the field of organ transplantation remains the nationwide shortage of donor livers, which has led to high patient mortality while waiting for a liver transplant. This could ultimately help address the national transplant shortage and lower mortality rates.”
He added: “Many donor livers are lost or fail soon after surgery because of damage that happens when blood flow is cut off and then restored. By identifying the protective proteins HuR and CEACAM1 that help the liver cope with this stress, our research could lead to treatments that keep more donor livers healthy. This means more patients could receive life-saving transplants, with fewer complications and better long-term outcomes.”
While promising, researchers caution against directly applying these findings to humans yet, as much of their work relied on genetic deletion methods specific to mice. The next phase will involve testing whether these protective switches can be activated in human livers maintained outside the body before transplantation.
The study included contributions from Brian Cheng, Tristan Tibbe, Dr. Siyuan Yao, Megan Wei, Zeriel Wong, Taylor Torgerson, Richard Chiu, Aanchal Kasargod, Dr. Kojiro Nakamura, Monica Cappelletti, Myung Sim, Dr. Douglas Farmer, Dr. Fady Kaldas, and Dr. Jerzy Kupiec-Weglinski—all affiliated with UCLA.
Funding came from several sources including grants from the National Institutes of Health (P01 AI120944, R01 DK062357, and R01 AI155856), support from the National Center for Advancing Translational Science under the UCLA Clinical and Translational Science Institute (UL1TR001881), and a fellowship from the National Science Foundation Graduate Research Fellowship Program (DGE-2034835).
