Projects

Preparing to put Liver on Pump

Liver on Pump

RNAi-based Therapeutics for Recurrent Hepatitis C Post Liver Transplantation

Recent developments in gene delivery and anti-viral application of RNA interference (RNAi) have increased the feasibility of molecular therapies for infectious diseases. We are developing new RNAi technologies for the delivery of multiple-target vectors that can be applied to combat chronic viral infections, specifically to reduce the likelihood of mutational outgrowth and reduce, if not eliminate, the chance of recurrent HCV post liver transplantation.
Hypothermic Machine Perfusion of Liver Grafts for Transplantation

Simple cold storage (CS) is the only form of liver preservation currently utilized. Machine preservation (MP) using continuous hypothermic perfusion has led to improved results in extended criteria donor kidneys and has been an area of interest in many animal liver transplant models. Machine preservation allows removal of waste products, delivery of metabolic substrates and maintenance of the microvascular integrity of the graft during the preservation period. Our faculty have pioneered this technique in liver transplantation. We have brought it from the preclinical arena to completing a clinical trial. The results of our federally funded (HRSA) Phase 1 trial have shown promise in improving early outcomes after liver transplantation.
Ex vivo Renal perfusion
Pulsatile Renal Preservation and Ex-Vivo Pharmacologic Manipulation

Long term pulsatile preservation with novel perfusates will be tested in large animal and human discard organ models. A normothermic oxygenated reperfusion model will allow histologic and functional evaluation of kidneys receiving novel perfusates or other protective agents in preservation injury.
Lentiviral Based Delivery of RNAi to Liver Grafts

Using the hypothermic machine perfusion system (project 2), we will explore the use of lentiviral delivery to perfused livers during cold and sub-normothermic temperatures to determine the extent of localization and deposition of vectors.
Xenotransplant/Incompatible Model

Using ex-vivo perfusion techniques, we have developed a robust "functioning kidney model" of incompatible transplantation and xenotransplantation. Collaborative projects with other departments investigating antibody-mediated rejection, complement activation, and cellular rejection are being designed using our ex-vivo kidney model.
Machine Perfusion of Extended Criteria Donor Livers for Transplantation

This study uses knowledge gained from the first clinical trial of machine perfusion in liver transplantation. Currently a clinical trial aimed at 25 patients, it will be conducted to evaluate the benefits of machine perfusion on graft outcome in ECD livers. Our hope is that more widespread use of these grafts will shorten the transplantation waitlist and lower the number of patients who die waiting for a transplant. In-depth molecular biology analyses will be employed to elucidate protective mechanisms. This project is funded by a Federal Grant from HRSA.