Novel Inducers of Hypometabolism for Preservation of Transplant Tissue
Abstract
The quality of grafts prior to transplantation is a significant factor influencing the success of this surgical procedure. However, damage of transplant tissue inevitably occurs as a consequence of inadequate blood flow (ischemia) after tissue procurement. Ischemia can lead to impaired graft function and contribute to graft rejection. With the shortage of transplant tissue, treatments to optimize the quality of and minimize injury to this tissue are a high priority. Procedures that induce hypometabolism (a state similar to suspended animation, characterized by abnormally low metabolism) are known to be beneficial; however, they also cause undesirable side effects. The goal of this proposal is to identify novel inducers of hypometabolism using the zebrafish embryo as a model system. The zebrafish is an ideal model with which to pursue this project as it can survive in complete absence of oxygen (anoxia) by entering into a reversible arrested state characterized by cessation of all cellular activity. This arrest can occur within minutes and is thought to conserve cellular energy (ATP), hence contributing to hypometabolism. Our working model is that low oxygen induces rapid changes in intracellular signaling molecules in zebrafish embryos that trigger arrest. We propose here to take advantage of the advanced genetic and screening capabilities of zebrafish to identify these key signaling molecules. Successful completion of our research goals is expected to have a positive impact since molecules that promote arrest are potential therapeutic targets for drugs that induce a hypometabolic state. Such drugs are highly relevant for the preservation of organs prior to transplantation and for treating patients undergoing surgery where ischemia is a concern.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610466
Entities
People
- Rachel Brewster
Organizations
- United States Army
- University of Maryland, Baltimore County