TILT: An alliance finding solutions for improving liver transplants

Roberto Gedaly, MD, and Francesc Marti, PhD, investigators in the University of Kentucky College of Medicine Department of Surgery, have noticed a year-over-year increase in liver transplants at UK HealthCare.

“Not only has our volume gone up significantly,” Dr. Gedaly said, “we’re actually going to break a record of liver transplant patients this year.”

Launched in 2020, the College of Medicine’s Alliance Research Initiative posed a structured opportunity for the two investigators to combine clinical and basic science expertise and become pioneers on a new modality of immunotherapy in solid organ transplantation. Considering Kentucky’s high incidence of liver disease – fueled in part by high rates of alcoholism, hepatitis C, obesity and diabetes – UK was the “right place” to conduct this type of clinical research.

Dr. Gedaly and Dr. Marti lead the “T Cells to Induce Liver Tolerance (TILT) Alliance,” a new team supporting translational and clinical research in transplantation and immunology. Their work with the Alliance stems from the effort they began in 2014 developing cell-induced immunosuppression, the use of a patient’s own regulatory T cells (white blood cells), as an alternative to drug-induced immunosuppression to prevent organ rejection.

In the process of a transplant, immunosuppression is used to prevent rejection. While drug-induced immunosuppression is effective, it can lead to major toxicity in patients. Using the human body’s cells instead could decrease or prevent the  use of toxic medications.

TILT team members are currently conducting an FDA-approved pilot study investigating the safety and effectiveness of administering regulatory T cells to renal transplant recipients. This is the only active clinical pilot study in Kentucky and the Appalachian region using these cells in solid-organ transplantation.

Along with the clinical trial, TILT Alliance members are mentoring junior faculty from across the University. They are also working together with the Biospecimen Bank and Tissue Procurement Shared Resource Facility of the Markey Cancer Center to study the phenotypic and mRNA abundance of liver resident regulatory T cells in a normal and transplanted liver.

Dr. Gedaly and Dr. Marti both have extensive experience in surgical transplantation and immunology. Dr. Gedaly the chief of the UK Transplant Center, and Dr. Marti is chief of the Transplant Cell Immunotherapy Laboratory.

The institutional support of the Alliance Research Initiative has led to the forging of cross-college and cross-University connections, the gathering of clinical and basic scientists for collaboration, and the development of preliminary data that will help TILT apply for large grants and publish high-impact articles.

“It’s necessary to have this kind of umbrella that brings us all together as clinicians and basic scientists,” Dr. Marti said.

TILT Alliance Team Members:

• Fanny Chapelin PhD, Research Assistant Professor – College of Engineering
• Roberto Gedaly MD, Chief of Transplantation Division – Department of Surgery
• Aman Khurana, MD, Assistant Professor – Department of Radiology
• Francesc Marti, PhD, Associate Professor – Department of Surgery