2026 DIG Research Project | "Microbial Modulation of Nrf2/HO-1 and TLR4 Signaling in Early Allograft Dysfunction After Liver Transplantation (MORTAL)"

Background

Elizabeth A. Wilson, MD, is an assistant professor of anesthesiology at the Duke University School of Medicine and a member of the General, Vascular, and Transplant Anesthesiology Division at Duke University Medical Center. A lifelong Duke fan, she grew up in Durham and Chapel Hill, NC. She went on to earn a BS in biology from Emory University and complete medical school at the Lewis Katz School of Medicine at Temple University, followed by a pediatrics residency at Duke University Medical Center (2014). She continued her training with a pediatric critical care medicine fellowship at Children’s National Medical Center (2017), an anesthesiology residency at The Johns Hopkins Hospital (2019), and a liver transplant anesthesiology fellowship at the University of California San Francisco (2021).

Wilson has received numerous honors, including multiple medical school scholarships, residency teaching awards, the Deborah W. Kredich Outstanding Senior Pediatric Resident Award at Duke, semi-finalist recognition for the Johns Hopkins Distinguished Teaching Society, and the Faculty Rising Star Award and Jerrold Levy Research Award during her tenure as faculty at Emory. She is an active member of the American Society of Anesthesiologists (ASA), International Anesthesia Research Society (IARS), International Liver Transplantation Society (ILTS), Society for the Advancement of Transplant Anesthesia (SATA), and the American Society of Transplantation (AST). Wilson has authored 12 peer-reviewed publications, with multiple currently under review. She has delivered invited lectures at national and international meetings, including the ILTS Annual Congress in Rotterdam, Netherlands (2023).

Wilson’s research focuses on how microbial signals modulate the cellular and immunologic mechanisms underlying ischemia reperfusion injury (IRI) and early allograft dysfunction (EAD) after liver transplantation (LT). Her long-term goal is to develop immunomodulatory and microbiome-based strategies to mitigate EAD and improve postoperative LT outcomes. Her interest in liver transplantation began during her anesthesiology residency at Johns Hopkins and deepened at UCSF, where she trained with leaders in hepatic IRI and biomarker research. As previous faculty at Emory, Wilson served as principal investigator on two funded studies: a prospective cohort study evaluating peri-reperfusion hyperoxemia and immune dysregulation in EAD (NIH/NCATS Georgia CTSA Pilot Grant and ILTS Vanguard Award), and a multicenter retrospective cohort study examining the influence of peri-reperfusion oxygen exposure on EAD after LT (ILTS Vanguard Award).

As faculty at Duke, Wilson is completing formal research training through the Anesthesiology T32 Program (GM08600) and coursework toward a Master of Health Sciences in Clinical Research through the Duke Clinical Research Training Program. She works in two translational laboratories: (1) the Duke Ex-Vivo Organ Laboratory (DEVOL) under Dr. Andrew Barbas, examining the cytoprotective and proinflammatory pathways driving IRI and EAD, and (2) the Duke Anesthesiology Microbiome Profiling (DAMP) laboratory under Dr. Mara Serbanescu, investigating how the microbiome shapes immune responses and influences perioperative and critical care outcomes.

Research

Wilson is the recipient of the 2026 DREAM Innovation Grant, a competitive award from Duke Anesthesiology’s DREAM Campaign that supports high-risk, high-reward research in anesthesiology, perioperative medicine, critical care medicine, and pain management. Her project, “Microbial Modulation of Nrf2/HO-1 and TLR4 Signaling in Early Allograft Dysfunction after Liver Transplantation (MORTAL),” examines how the peri-implantation balance between these cytoprotective and proinflammatory pathways contributes to EAD after LT, and whether the Nrf2/HO-1 and TLR4 regulatory axis is influenced by microbial DNA components translocating from the gut to the liver through the portal venous circulation peri-implantation.

EAD, defined as hepatic insufficiency within a week of LT, occurs in 20-25% of recipients and markedly increases the risk of allograft failure, morbidity, and mortality, including a tenfold higher chance of death within six months. Its primary driver, IRI, is a self-perpetuating cascade of cellular and immune disturbances triggered by temporary deprivation and subsequent restoration of oxygen. As reliance on marginal quality allografts, which are more susceptible to IRI, increases to meet growing demand for LT, the incidence of EAD is expected to rise. Identifying molecular drivers and modifiable triggers of EAD is therefore critical for developing targeted perioperative therapies.

Preclinical studies indicate Nrf2/HO-1 and TLR4 signaling operate as a regulatory axis that governs the balance between cytoprotection and inflammation during hepatic IRI. Separately, hepatic IRI is linked to TLR4 activation by gut-derived microbial components entering the portal circulation, with emerging evidence suggesting the composition of these portal venous microbial components (PV-MC) heavily influences the direction (activation or suppression) of downstream TLR4 proinflammatory signaling. In human EAD, however, the interaction between Nrf2/HO-1 and TLR4 pathways and the role of PV-MC in modulating this regulatory axis remains entirely unexplored.

This pilot, prospective, single-center observational study will enroll 34 deceased-donor LT recipients whose allografts are maintained on normothermic machine perfusion. Allograft tissue, serum, and rectal samples will be collected peri-implantation for protein and gene expression profiling and microbial analysis. This will be the first study to test whether the peri-implantation imbalance between Nrf2/HO-1 and TLR4 signaling correlates with EAD severity. Its innovative design introduces a novel gut-liver paradigm that challenges the traditional view of IRI as a sterile process by implicating PV-MC as modulators of cytoprotective and proinflammatory signaling. The study also aims to identify specific protein, gene, and microbial signatures as potentially modifiable triggers of EAD, laying the groundwork for future immunomodulatory and microbiome-based therapeutic strategies.

In addition to generating preliminary mechanistic data, Wilson’s work will establish a unique biobank to support future NIH applications focused on the influence of PV-MC on ferroptosis during EAD and the development of targeted interventions to mitigate EAD and improve postoperative LT outcomes. Wilson is collaborating with a multidisciplinary team of experts, including Dr. Andrew Barbas  and Dr. Stuart Knechtle (Duke Abdominal Transplant Surgery), Dr. Jamie Privratsky and Dr. Mara Serbanescu (Duke Anesthesiology), Dr. Ben Hughes (senior research associate, DEVOL), and biostatistician Mary Cooter Wright (Duke Anesthesiology).