Transplant Surgery Research
Research in the Division of Transplant Surgery at UAB
Translational and basic research is what distinguishes academic centers and transplant programs. The UAB Research programs have been at the forefront of immunosuppressant development and opportunities for basic and translational research are available within the division for Transplant Fellows and Residents.
The focus of the basic research is on ischemia/ reperfusion injury that occurs both before and during procurement, cold storage and the transplant procedure. We have developed unique models (brain death) to help understand the pathophysiology and guide therapeutic interventions.
Additionally, UAB is one of seven centers designated by the NIH an Islet Resource Center and provides a unique environment to study islet biology, engraftment and function after transplantation in both human and animal models. Listed below are some of the major resources and initiatives underway within the transplant division.
Islet Resource Center
The Islet Cell Resource Centers (ICRs) is funded by the National Center for Research Resources and the National Institute of Diabetes and Digestive and Kidney Diseases (U42 RR023246-01), components of the National Institutes of Health, Department of Health and Human Services. The ICR is currently comprised of 7 academic laboratories working towards three major goals: 1) to provide pancreatic islets of cGMP-quality to eligible investigators for use in FDA-approved, IRB-approved transplantation protocols; 2) to provide pancreatic islets for basic science studies; and 3) to optimize the harvest, purification, function, storage, and shipment of islets while developing tests that characterize the quality and predict the effectiveness of islets transplanted into patients with diabetes mellitus.
In the past year, the UAB ICR has performed over 33 allograft islet isolations for research purposes and over 28 autograft islet isolations for patients undergoing a partial or full pancreatectomy as a result of chronic pancreatitis. Currently, the UAB ICR is ranked 2nd among the ICR Consortium for both quality and productivity.
Brain Death Model
Clinical and experimental studies from our laboratory demonstrates organs from BD donors are typically characterized by diminished organ perfusion, deteriorated function, a higher incidence of acute and chronic rejection and shorter graft survival compared to living donors. Several studies demonstrated deterioration of organs follow brain death (BD) by multiple interrelated events, including the effect of massive acute cerebral injury, hypotension, and circulating factors. BD is characterized by extensive cortical necrosis that stimulates multiple cell types to release proinflammatory cytokines (PICs), such as tumor necrosis factor-a (TNF-a), interleukin-1b (IL-1b), interleukin-6 (IL-6), and interferon-c (IFN-c). PICs have a profound impact on pancreatic b-cell function and death during type I diabetes and PIT. We are currently focusing on strategies specifically to prevent or limit the detrimental effects of BD on organ transplantation using 3 animal models: murine, porcine, and non-human primate.
Liver ischemia with consequent reperfusion results in a multitude of cellular, humoral, and biochemical events leading to Hepatocellular injury and dysfunction. Hepatic ischemia/reperfusion (IR) injury is a significant complication in liver transplantation that can predispose patients to a profound reperfusion syndrome, resulting in primary graft nonfunction and initial poor function of the graft.
Recently, nitrite (NO2) has gained attention for its ability, at low concentrations, to protect tissues (including heart, liver, lung, brain) against ischemia/reperfusion (I/R) injury and represents an attractive therapeutic approach due to safety, efficacy, and relative low cost.
Recent studies are focused on providing the foundation for future mechanistic studies to elucidate the molecular events associated with NO2, BD, and islet transplantation and establish rational interventional therapeutic strategies to combat diabetes.
In the adult, inflammation and angiogenesis become co-dependent processes, wherein several cell types and biologic mediators interact in a highly regulated manner to promote repair and maintenance of vascular integrity. Ongoing efforts have demonstrated that fibroblast growth factor (FGF) and alternative splicing of the high affinity FGF receptor, FGFR-1, play a crucial, pivotal role in the vascular response to acute injury along with the development and the etiology of several pathophysiologic conditions including neurogenesis, tumorgenesis, arthritis, atherosclerosis, diabetes, wound repair, and organ transplant dysfunction.
The University of Alabama at Birmingham provides an outstanding clinical research environment with a track record of participation in both NIH and industry sponsored research. The clinical trials unit provides robust management for clinical protocol execution with a staff of one full-time regulatory coordinator, 6 full-time research nurse coordinators, 3 full-time study coordinators, 1 laboratory assistant, and 3 full-time office support staff. The current Renal Transplant research portfolio consists of 13 active studies (4 NIH and 7 Industry-supported) while the Liver Transplant research portfolio consists of 6 industry-sponsored studies. The School of Medicine at UAB provides additional resources for clinical research, especially via the NIH-sponsored Center for Clinical and Translational Science (CCTS). The structuring of new clinical research opportunities under this Center will provide additional support in the execution of clinical research throughout UAB.