# Defining Immunology Frailty as a Predictor of Human Liver Allograft Recipient Futility

> **NIH NIH K08** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2020 · $187,963

## Abstract

Project Summary/Abstract
DESCRIPTION: This application for a Mentored Clinician Scientist Development Award (K08) is designed to
evaluate the effect of cirrhosis-induced immune dysfunction on liver transplant outcomes. The candidate is a
transplant surgeon and immunologist whose long-term goal is to develop treatments to prevent immune frailty and
improve liver transplant recipient survival. In order to fulfill the educational objectives of this award, this proposal
will expand the applicant’s knowledge base into novel lines of translational research inquiry and delve into new
areas of investigation requiring focused mentorship. The mentors assisting in the applicant’s development will be
crucial for her success, for the performance of the proposed studies, and for the educational mission of the award.
Xian Li, PhD, a leader in basic science immunology, and Mark Ghobrial, MD, PhD, a leader in clinical and
translational research, will serve as co-mentors. They will be assisted by Drs. Dale Hamilton and Anisha Gupte,
who will provide mentorship in bioenergetics; Dr. Ed Graviss, who will provide expertise in biostatistics; Dr.
Wenhao Chen, who will provide expertise in T cell exhaustion, and Dr. Todd Eagar, who will provide expertise in
inflammation. A rigorous career development plan will be implemented, including structured workshops,
biostatistics course work, scientific seminars, and lab meetings. This combination will be instrumental in ensuring
the candidate’s successful transition to a career as an independent investigator.
PROJECT SUMMARY: Due to organ shortage, livers are transplanted in order of recipient medical urgency;
however, ethical principles dictate avoidance of futile transplantation. Due to imbalance in supply and demand for
organs, illness severity (categorized by MELD score) has drastically increased. MELD does not correlate well with
risk of death post-transplant; thus, better metrics to evaluate risk of mortality are necessary. The most common
cause of death early after liver transplant relates to consequences of an immune system which is frail or
dysfunctional prior to transplant. In pre-transplant cirrhotics, immune frailty may relate to metabolic deficiencies or
T cell exhaustion and may affect liver transplant outcomes. Based on this, it is hypothesized that the pre-transplant
state of immunologic frailty results from cirrhosis-related alterations in recipient metabolism, resulting in global T
cell metabolic dysfunction, increased T cell exhaustion, and limited adaptive immune proliferation and function.
Persistence of immunologic frailty following liver transplant results in increased recipient mortality. This will be
addressed by three Aims, which will (1) evaluate metabolic alterations in liver transplant recipients and determine
the bioenergetics pathways involved in immune frailty, (2) examine the role of T cell exhaustion in immune frailty,
and (3) determine the longitudinal effect of frailty on the recipient post-t...

## Key facts

- **NIH application ID:** 10079581
- **Project number:** 7K08DK118187-02
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** Keri Elizabeth Lunsford
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $187,963
- **Award type:** 7
- **Project period:** 2019-04-10 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10079581

## Citation

> US National Institutes of Health, RePORTER application 10079581, Defining Immunology Frailty as a Predictor of Human Liver Allograft Recipient Futility (7K08DK118187-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10079581. Licensed CC0.

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