Transplant Research Thrives Through Collaboration

This story was published in the June 2024 issue of the Breakthroughs newsletter.

A map of the Northwestern University Transplant Outcomes Research Collaborative (NUTORC) Network looks like an intricate spiderweb. Hovering over one investigator’s name, you see the many investigators they are connected with through publications and research collaboration. This visual represents the wide web of investigators and clinicians needed to address the complex challenges that face organ transplantation.

According to Daniela Ladner, MD, MPH, the Comprehensive Transplant Center and the Division of Organ Transplantation in the Department of Surgery have a rich history of research. She is the founding director of NUTORC and serves as the vice chair of Research and Innovation in the Department of Surgery, the John Benjamin Murphy Professor of Surgery and Professor in the Department of Surgery and of Medical Social Sciences in the Division of Determinants of Health.

Ladner was recruited to Northwestern in 2008 to build a research program around transplant outcomes. Through NUTORC, she has brought together investigators from a variety of disciplines[MR1]  across Northwestern University including engineers, economists, social scientists, biostatisticians and more to help answer pertinent questions in transplant outcomes and policy.

“The goal of NUTORC is to bring together transplant clinicians and methodological experts across the disciplines to advance the field through cutting-edge science,” Ladner said.

To develop better outcomes for transplant patients and to inform policy that supports organ transplantation, Ladner and her colleagues have received many NIH grants, including one to study the impact of the African American Transplant Access Program.

Founded by the Northwestern Medicine in 2019, the African American Transplant Access Program (AATAP), is led by Dinee C. Simpson, MD, associate professor of Surgery in the Division[MR3]  of Organ Transplantation. In September 2023, the program received funding through a grant from the National Institute of Diabetes and Digestive and Kidney Diseases to further study the impact of the program on patients and to reproduce the AATAP program at another center in Florida. This project is led by Simpson in partnership with Kiarri Kershaw, PhD, MPH, associate professor of Preventive Medicine in the Division of Epidemiology, and Ladner.

One collaborative project includes a partnership with Northwestern University Data Coordinating Center (NUDACC). Ladner and her collaborator, Jody Ciolino, PhD, Associate Professor of Preventive Medicine in the Division of Biostatistics, have received funding to serve as the Scientific and Data Coordinating Center for the Liver Cirrhosis Network (LCN), a the 10-center consortium to study  cirrhosis. Other collaborative projects include collaborations with the Weinberg School of Arts and Sciences and the School of Engineering sponsored by the National Institute of Aging and the National Institute of Diabetes and Digestive and Kidney Diseases.

Research that sheds lights on transplant tolerance, outcomes and even devices to monitor an organ transplant are some of the many advancements [MR5] that has been published in the field.

A study published in JAMA Surgery found that liver transplant recipients who meet the criteria for physical frailty have worse quality of life post-transplant compared to non-frail patients.

To better understand the connection between frailty and post-transplant health-related quality of life in patients with cirrhosis of the liver, investigators surveyed 358 liver transplant recipients who previously participated in the Functional Assessment in Liver Transplantation study, a multicenter, prospective observational cohort study of liver transplant patients – a longstanding partnership between Northwestern and UCSF.

Co-authors on the study included Ladner, Daniel Ganger, MD, professor of Medicine in the Division of Gastroenterology and Hepatology and of Surgery in the Division of Organ Transplantation, and Andres Duarte, MD, PhD, professor of Medicine in the Division of Gastroenterology and Hepatology and of Surgery in the Division of Organ Transplantation.

Other recent research includes a publication in the Journal of Clinical Investigation, which identified how the immune system can regulate organ rejection in mice. These findings may be useful for improving transplant tolerance in human, according to study co-author Zheng Zhang, MD, research professor of Surgery in the Division of Organ Transplantation.

Moving forward, Zhang and her collaborators at the University of Chicago will continue to study the mechanisms underlying transplant tolerance and the inflammatory events that make tolerance vulnerable, she said.

“By understanding this mechanism, we hope that we can actually find a way to make grafts more resistant to the detrimental effects of infections,” Zhang said. “These results will help clinicians design therapeutic interventions that can help sustain long-term tolerance.”

A study published in the Science outlined the development of the first electronic device to continuously monitor the health of transplanted kidneys in real time. This work was led by scientists at Northwestern including John Rogers, PhD, the Louis Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering and Neurological Surgery.

After the success of the small animal model trial, Rogers and his team are now testing the system in a larger animal model. They are also evaluating ways to recharge the coin cell battery in the device so that it can last a lifetime.

While the primary studies were conducted with kidney transplants, the investigators assume it could also work for other organ transplants, including the liver and lungs, and for other disease models.

“This research goes way beyond the Division of Organ Transplantation, even the Feinberg School of Medicine,” Ladner said. “It’s often transdisciplinary and together we can do something that creates a new space of investigation.”

In addition to the exceptional research, Northwestern Medicine’s Division of Organ Transplantation, founded in 1964, is a leader in field. This May marked 10,000 abdominal transplants performed at the center. According to 2023 data from the United Network for Organ Sharing, Northwestern Medicine’s organ transplant program is seventh in the U.S. for the highest number of kidney transplants performed and third for kidney/pancreas transplants.

“We’re really in a renaissance of transplant right now, and it’s really exciting to see where transplant was and, more importantly, where transplantation is going,” says Satish Nadig, MD, PhD, director of Northwestern’s Comprehensive Transplant Center, chief of Organ Transplantation in the Department of Surgery, the Edward G. Elcock Professor of Surgical Research, and a professor of Microbiology-Immunology and of Pediatrics.

“The fact that we’ve hit 10,000 [transplants]not only allows us the opportunity to say we’ve saved more lives than most transplant programs in the country, but also gives us the experience to be on the forefront of the next era of transplant science.”

Olivia Dimmer and Kristin Samuelson contributed to this story.