The Transplant Forum at Columbia University Medical Center is dedicated to raising awareness and funding for transplantation research across all organ disciplines. To learn more about ongoing research in liver transplantation, please see several projects highlighted here:
Adult Liver Transplant
Tomoaki Kato, MD, Megan Sykes, MD, and Adam Griesemer, MD
Drs. Kato, Sykes and Griesemer, are developing a method of combining bone marrow and liver transplantation in a large animal model, with the goal of achieving induced tolerance that can be rapidly translated into clinical trials. This technique—a combined liver and bone marrow transplant—could benefit patients with blood diseases that lead to loss of liver function. An example of such a disease is sickle cell anemia. The CCTI is now working together with Columbia’s liver, adult bone marrow, and pediatric bone marrow transplant teams to plan a trial of combined liver and bone marrow transplantation in this setting. This could be an exciting clinical application for current patients.
Benjamin Samstein, MD, Alyson Fox, MD
Living donation presents a tremendous opportunity to increase the number of organs available for transplantation and save the lives of individuals waiting for transplant surgery. Our scientists and clinicians are working to develop protocols that will make living donation even safer, protecting the health of the donor as they make this amazing gift of life.
Elizabeth Verna, MD
Dr. Verna is monitoring the gut microbiome of patients with liver disease, looking for clues to optimize recovery after a transplant. This research is part of a four-year project funded by the National Institute of Diabetes and Digestive and Kidney Diseases to illuminate the role of the intestinal microbiome in recurrent disease following liver transplantation. Chronic liver disease damages the gut barrier and triggers shifts in gut ecology to favor more pathogenic organisms, leading to inflammation and scarring in the liver. To study this disease mechanism, Dr. Verna is examining liver transplant patients, since these patients have an abnormal intestinal microbiome at the time of transplant. Dr. Verna is collecting biological samples from patients before a transplant and in the months and years following the procedure, using 16S rRNA sequencing to track the patients’ digestive microbes. These studies will help establish biomarkers for liver disease recurrence and could provide a guide for how to target specific microbes or metabolic pathways in order to maximize transplant outcomes.
Pediatric Liver Transplant
Megan Sykes, MD, and Adam Griesemer, MD
Drs. Sykes and Griesemer are working to induce tolerance to liver transplants in large animals. This is a necessary step to developing a safe and effective protocol for human transplant patients. Tolerance induction has the potential to fundamentally change our approach to organ transplantation. Although there has been significant improvement in the immunosuppressive drugs that prevent organ rejection among transplant recipients, these medications still cause significant side effects. Inducing tolerance would prevent patients from relying on immunosuppressives, greatly improving long-term outcomes. Tolerance is also an important step in making xenotransplantation—the use of donor organs from other species—a possibility, since the amount of immunosuppression required to avoid rejection of an animal organ in a human patient would be unacceptably high. Xenotransplantation is key to supplementing the limited supply of transplant-ready human organs,
Megan Sykes, MD, and Mercedes Martinez, MD
Recurrent disease following liver transplantation is one of the leading causes of organ rejection and health problems for patients with autoimmune liver disease, yet the biological mechanisms that cause recurrence are not well understood. We are now able to identify and follow the specific lymphocytes—blood cells in the immune system—that are responsible for liver rejection. These same lymphocytes are also involved in the liver damage that occurs with recurrent autoimmune liver disease. Drs. Sykes and Martinez are developing techniques to help distinguish between recurrent autoimmune liver disease and organ rejection so that an accurate diagnosis—and the appropriate treatment—can be reached.
Megan Sykes, MD, and Mercedes Martinez, MD
Drs. Sykes and Martinez are investigating a TCR (T cell receptor) sequencing method that has the potential to identify tolerance among transplant recipients. TCR sequencing can identify and trace the specific lymphocytes (immune cells) responsible for acute rejection. Drs. Sykes and Martinez hypothesize that if these cells disappear from a transplant receipient, this could indicate that tolerance has been achieved and that immunosuppression can be decreased. Their goal is to determine if it is safe for patients to slowly reduce and then completely stop immunosuppression drugs.