A Prospective, Long-Term Confirmatory Follow Up Trial in Highly Sensitized Patients Treated with Imlifidase or Standard of Care in the ConfIdeS (20HMedIdeS17) Trial  - PI:  Anderson, Douglas J.

An open-label, controlled, randomized Phase 3 trial evaluating 12-month kidney function in highly sensitized (cPRA >99.9%) kidney transplant patients with positive crossmatch against a deceased donor, comparing desensitization using Imlifidase with standard of care - PI:  Anderson, Douglas J.

Global Utilization And Registry Database for Improved preservAtion of doNor LIVERs (GUARDIAN-LIVER) – PI:  Cannon, Robert M.

HOPE in Action Prospective Multicenter, Clinical Trial of HIV+ Deceased Donor Liver Transplants for HIV+ Recipients – PI:  Cannon, Robert M.

UAB Hepatobiliary Tumor Clinical Outcomes – PI:  Cannon, Robert M.

Spatial Epidemiology in Solid Organ Transplantation – PI:  Cannon, Robert M.

Liver Resection for Hepatic Lesions after Liver Transplantation – PI:  Cannon, Robert M.

Enhanced Recovery After Hepatobiliary Surgery – PI:  Cannon, Robert M.

ECMO DCD Database – PI:  Cannon, Robert M.

Determining the Optimal Timing of Administration of Direct Acting Antivirals to Patients with Hepatitis C-Associated Hepatocellular Carcinoma Undergoing Liver Transplantation – PI:  Cannon, Robert M.

HLA Immunogenetics and Kidney Allograft Outcomes

Transplant Data Analysis Center (TDAC) Data Collection for All Renal, Renal/Pancreas, Liver, Intestinal, Heart, Lung and Heart/Lung Transplants – PI:  MacLennan, Paul

Genetic, Environmental, and Histologic Basis for Kidney Disease Risk among Persons Living with HIV – PI:  MacLennan, Paul

Graft and Quality of Life Outcomes of Uterus Transplantation – PI:  Porrett, Paige

Endometrial Immunobiology in Uterus Transplantation – PI:  Porrett, Paige

Mechanisms of Uterine NK Cell Differentiation – PI:  Porrett, Paige

Sponsor-Initiated OCS Liver Perfusion (OLP-II) Registry – PI:  Sheikh, Saulat S.

Bio Defense G 3 Use in Vascular Access Creation – PI:  Young, Carlton J.

Review of Transplant Outcomes in Kidney/Pancreas Recipients at University of Alabama at Birmingham – PI:  Young, Carlton J.

Evolution and Durability of Human T and B Cell Responses - Project 2 - Genesis and dynamics of human endometrial resident memory T cells revealed by uterus transplant recipients (*SubProject*)

PI: Lund (Porrett subproject PI)

U19AI181105

This research focuses on tissue resident memory T cells (TRM), a crucial component of the immune system that resides in various tissues, including the human uterine endometrium. While most studies on T cells have focused on peripheral blood and secondary lymphoid organs, tissue-specific environments significantly influence immune cell behavior, making these studies less applicable to tissue-resident cells. The uterine endometrium presents a unique environment, undergoing repeated cycles of tissue loss and regeneration, which may influence TRM recruitment, composition, and longevity in distinct ways compared to other tissues.

The study combines advanced next-generation sequencing techniques with samples from healthy control volunteers and uterus transplant recipients to investigate TRM trafficking and differentiation. The goal is to fill the gap in understanding tissue-specific immune responses, with potential applications for women's health, transplant recipients, vaccines, and cancer therapies. Ultimately, the research aims to expand our ability to modulate the immune system and improve treatment strategies for a variety of diseases.

AIM 1.  Study the origin and durability of resident memory T cells in human endometrium during steady state and rejection.

AIM 2.  Identify the transcriptional programs and tissue signals that govern endometrial TRM residence.

Uterine Transplant and Tissue-Resident Natural Killer (trNK) Cells

PI: Porrett

R01AI177369

This project aims to enhance our understanding of pregnancy complications in organ transplant recipients, particularly focusing on pre-eclampsia and fetal growth restriction. Historically, studying pregnancy in this population has been challenging due to the small number of reproductive-age transplant recipients and concerns about maternal and fetal health.

To address these challenges, the study leverages a unique cohort of uterus transplant recipients, who experience high rates of pregnancy complications, potentially due to disruptions in uterine natural killer (uNK) cell function. These cells play a crucial role in placental development, and prior research suggests that immunosuppressive medications used by transplant recipients may affect their survival, localization, and function, leading to pregnancy complications.

Using uterus transplantation as a model, the project investigates the molecular mechanisms underlying uNK cell dysfunction through advanced single-cell technologies, flow cytometry, imaging studies, and in vivo mouse models. By filling critical knowledge gaps in reproductive immunology, the findings aim to improve maternal health outcomes for transplant recipients and potentially for all women.

AIM 1.  Identify mechanisms of trNK homeostasis by testing the hypothesis that NFAT mediates IL-15 signals governing trNK residency and survival.

AIM 2.  Examine trNK cell development by testing the hypothesis that NFAT is required for IL-15-mediated trNK effector differentiation and maturation.

AIM 3. Test the hypothesis that NFAT blockade limits spiral artery remodeling by preventing VEGF release and KIR activation of trNK.

Robert Cannon, M.D.

Dr. Cannon’s research addresses geographic disparities in organ transplantation, focusing on liver and kidney transplantation and the influence of social determinants of health (SDOH). For liver transplantation, variations in Model for End-Stage Liver Disease (MELD) scores across regions, particularly due to MELD exception points, contribute to disparities in access. Research suggests that treating MELD scores as fixed across geographic areas fails to account for regional variations in mortality risks due to differing social and healthcare factors. Dr. Cannon is interested in the development of a more granular MELD exception system that incorporates regional SDOH differences to mitigate these disparities.

For kidney transplantation, geographic differences in waitlist rates and transplant outcomes are evident, particularly in the Southeast U.S., where high rates of end-stage renal disease (ESRD) coincide with lower transplant rates. The research advocates for metrics that consider ESRD patient density, rather than just waitlist size, in evaluating transplant center performance. Additionally, social vulnerability, as measured by the CDC's Social Vulnerability Index (SVI), plays a significant role in access to both kidney and liver transplants. Dr. Cannon’s research is focused on the creation of a new SDOH index specific to transplantation, which would better reflect the impact of social factors on access to transplant services and guide future transplant policy. The overall goal of Dr. Cannon’s research is to develop a robust measure of SDOH that will contribute to a more equitable transplant allocation system, with a focus on both MELD exception points and social vulnerability.