For end-stage diseases, organ transplantation is the ultimate treatment; however, the organ supply consistently underwhelms the demand. Adding to the reality of a globally growing transplant list is the need for a reliable technology to accurately determine if organs are suitable for transplant and to increase the number of these suitable organs.
Carnegie Mellon University’s Ren Lab, University of Pittsburgh Medical Center (UPMC) and University of Wisconsin-Madison are teaming up to reshape current practice related to organ transplants, by introducing a novel platform to study protein dynamics within the donor graft. The platform can be used to discover novel biomarkers to evaluate organ quality after donation, but before transplantation, as well as to reveal new therapeutic targets to improve donor organ function.
Most if not all biological processes are mediated by protein molecules, and changes in production and turnover of proteins are important to note. Current methods to study protein dynamics using mass spectrometry are generally good at detecting the most abundant proteins. They fall short in capturing what happens to proteins of low abundance, such as newly produced proteins that carry critical information related to donor organ function and injury response.
This engineering approach aims to bring donor organs back to life, to tell their ongoing story in terms of pathogenic protein production.Zihan Ling, Ph.D. student, Biomedical Engineering
“We’ve developed a new technology that we’re calling newly synthesized glycoprotein profiling, to enable the characterization of proteins being newly produced within a short timeframe of a few hours, to better understand what a donor organ is going through, and how it correlates with the transplantation outcome,” explained Zihan Ling, first author of the work published in American Journal of Physiology and biomedical engineering Ph.D. student.
Ling continued, “This engineering approach aims to bring donor organs back to life, to tell their ongoing story in terms of pathogenic protein production. By focusing on newly produced proteins, we can illuminate key details about the cause of an injury, not just the consequence. Understanding how the organ is injured at the protein level will help us better assess organ quality, so we can predict if it will cause serious complications after transplantation.”
The group’s initial investigation was conducted through an animal research study and centered on identifying molecular signatures of warm ischemic injury in lungs. Findings are broadly applicable, however, and could translate to similar procedures for the heart, kidney, liver, and other organs. Future-state, the group plans to test their technology platform on human lungs.
We believe this work has the potential to lead to dramatic improvement in donor organ quality and transplantation outcomes and ultimately to help alleviate donor organ shortage.Charlie Ren, Associate Professor, Biomedical Engineering
“A big part of engineering research is making your process so robust, so reliable, that you can ask very detailed questions,” explained Charlie Ren, associate professor of biomedical engineering. “We’ve been able to execute a highly relevant protein discovery program to see what’s happening in the donor organs. We believe this work has the potential to lead to dramatic improvement in donor organ quality and transplantation outcomes and ultimately to help alleviate donor organ shortage.”
This research was funded in part by the National Institute of Health. Additional study authors include Pablo Sanchez, UPMC associate professor of surgery; Kentaro Noda, UPMC research assistant professor; Lloyd Smith, professor at University of Wisconsin-Madison; and Brian Frey, research scientist at University of Wisconsin-Madison.