Paul I. Terasaki Chair in Surgery at UCLA
Many patients die on the transplant waiting lists due to a shortage of quality donor organs.
Dr. Jerzy Kupiec-Weglinski wants to save the lives of these patients. He develops novel treatments that improve the quantity and quality of organs available for life-saving liver transplantation. By increasing the quality of organs, the treatments also boost long-term liver function.
"If we have more organs, we can transplant more people, and we can save more lives," says Dr. Kupiec-Weglinski.
UCLA's Division of Liver Transplantation is one of the largest liver transplant programs in the United States. The division has performed over 6,200 human liver transplants since Dr. Ronald Busuttil, the current Department Surgery Chairman, founded it in 1984. Over 90% of the center's transplant recipients survive for over a year after surgery.
Unfortunately, due to the aging of our general population, the quality of the organ supply has fallen behind procedural advances.
"About 15% of donor livers are never transplanted; they are discarded because of poor quality," says Dr. Kupiec-Weglinski.
To increase our viable organ supply, Dr. Kupiec-Weglinski's lab develops treatments to improve the quality of livers we might otherwise discard. The treatments focus primarily on ischemia/reperfusion injury (IRI), which occurs as an organ loses, and subsequently regains, blood and oxygen flow. IRI takes place in the time between organ harvesting and transplantation. For Dr. Kupiec-Weglinski, this is the "window of opportunity" to improve the function of donor livers.
Dr. Kupiec-Weglinski's lab first uses cell culture systems and small animal transplant models to experiment with novel treatment regimens designed to improve the quality of donor livers. After these initial tests, the researchers determine if any results or observations might translate to humans.
Step 1: Researchers determine which treatments might improve liver quality by analyzing cellular interactions in well-defined in vitro culture systems—both with and without drugs.
Step 2: Researchers test the treatments in small (mouse/rat) and large (pig) animal models.
Step 3: Leveraging findings from the test tubes and animal settings, researchers determine if the treatments might improve the quality of human livers by examining biomarkers to see if they are the same in human clinical and animal settings.
Dr. Kupiec-Weglinski says this process helps bridge animal models and the clinical enterprise. It elucidates how to improve outcomes and helps researchers determine if drugs used in animals can also be successfully used in humans.
As ischemia/reperfusion injury (IRI) negatively affects both early and late transplant outcomes, an effective treatment could save lives by increasing the quality of livers available and making livers last longer; an IRI treatment may ward off chronic rejection, which can lead to the loss of organ function and even death.
Dr. Kupiec-Weglinski is well-positioned to isolate a liver rejuvenation treatment that is both safe and effective for humans. He has one of the best-funded transplant grants in the country—$12 million from the National Institutes of Health.
Dr. Kupiec-Weglinski's work inspires optimism for other transplantable organs as well, because as he says, "certain mechanisms of tissue damage or rejection are the same regardless of the tissue." For example, he's working to translate his findings on livers to the field of composite tissue transplantation (e.g., limbs and face). This would bolster the scientific foundation of a promising young field with nascent procedural precedent.
As for Dr. Kupiec-Weglinski, he's inspired by how much progress the field has made. He attributes this progress to collaborations, such as the I3T research theme, that bring together UCLA-based researchers and physicians from different fields.
"When I started my career at Harvard in 1979, the one year liver transplant survival rate was less than 40%. Now it's 90%—more than double. It's very rewarding because more and more patients are getting life-savings organs," says Dr. Kupiec-Weglinski.