A variety of research programs are underway at UPMC Children’s Hospital of Pittsburgh Transplant Program in conjunction with the Thomas E. Starzl Transplantation Institute. Many projects are directly related to liver transplantation and may prove to enhance transplantation procedures and success rates.
Some of the programs focus on:
- Immunotherapy
- Transplantation tolerance
- Organ preservation
- Growth factor biology
- Bioengineering
Seeking the secrets of transplant tolerance
Pediatric liver transplant surgeon George Mazariegos, MD, is heading up a research team at the Thomas E. Starzl Transplantation Institute that is studying specific biological factors that may enable some patients to be successfully weaned from immunosuppressants. The investigation is part of a three-year grant funded by the National Institutes of Health via the Immune Tolerance Network. Researchers from nearly 40 institutions are involved.
Dr. Mazariegos and colleagues are collecting blood samples from adult and pediatric patients who have successfully been weaned from all immunosuppressive therapy. Information collected from these individuals will be compared to information collected from patients who rejected their transplant after withdrawal from immunosuppressants; patients with acute rejection despite continuing immunosuppression therapy; and patients currently undergoing immunosuppression withdrawal.
If precise clinical markers can be determined, it may be possible to develop simple tests that could help predict transplant tolerance. The research may also provide clues in understanding how tolerance impacts autoimmune diseases and other health problems, such as allergies and asthma.
Other co-investigators involved in this research at the Starzl Transplantation Institute include: Adriana Zeevi, PhD; Angus Thompson, PhD, DSc; and Jorge Reyes, MD.
Liver and Intestine Transplantation
Dr. George Mazariegos, who holds the Jamie Lee Curtis Endowed Chair in Pediatric Transplantation, is coordinating clinical efforts to safely minimize immunosuppressive medications after liver transplantation. The goals of this clinical practice are to maximize quality of life and minimize the undesirable side effects of immunosuppressive therapy while maximizing long-term liver function.
Dr. Mazarriegos has also collaborated with colleagues at the Thomas E. Starzl Transplantation Institute to develop simple blood tests that can be drawn with a patient’s regular blood work in order to help determine their likelihood of rejection or the possibility of lowering immunosuppressive medications. This “tolerance assay” is funded by the Immune Tolerance Network, an international multidisciplinary organization funded by the NIH.
Rakesh Sindhi, MD, professor of surgery, is director of the Pediatric Transplant Research effort. Funded by the National Institutes of Health for several years, Dr Sindhi’s laboratory monitors cellular immune responses in children, who have received liver and intestine grafts. Also under evaluation at the genome-wide level are the genetic factors that mediate the different cellular responses, as well as different immune outcomes after transplantation-rejection, non-rejection and tolerance.
Preliminary results show that events favoring one outcome over the other are initiated at first contact between the host and the graft. One cell type that identifies those at risk for rejection is the T-cytotoxic cell, a type of T-lymphocyte. This cell type is being evaluated as a clinical biomarker for all transplant recipients to facilitate safe and personalized drug minimization strategies.
A secondary objective of the laboratory is to develop novel clinical trial designs that can be implemented for drug development in children. The laboratory also trains post-doctoral associates in transplant immunology.
Co-investigators include Adriana Zeevi, PhD, director of Tissue Typing and professor of Pathology, and Daniel Weeks, PhD, professor of Human Genetics and Biostatistics at the University of Pittsburgh.
