# Project 4-Animal transplant models to characterize immune and regenerative effects of alcohol

> **NIH NIH P50** · JOHNS HOPKINS UNIVERSITY · 2020 · $351,900

## Abstract

SUMMARY
Early liver transplant (ELT) without period of 6 months abstinence has become a life-saving therapy for
severe alcoholic hepatitis (SAH) patients. Chronic and active alcohol abuse impacts innate and adaptive
immunity and predisposes to infections. This susceptibility is further complicated by immunosuppressive
therapy after LT. Further, living donor liver transplant (LDLT) is considered for patients with SAH especially
when the patient has a statistically low priority for cadaveric organ transplantation based on the allocation
system. However, the impact of active alcohol abuse on alloimmunity is largely unknown. Alcohol use also
damages bone marrow stem cells that may be important for liver regeneration, raising a concern for LDLT. By
using our established rat liver transplantation model our studies address the two serious problems in ELT for
patients with SAH: immunosuppressive therapy and using a living donor for LT. We hypothesize that chronic
and active alcohol abuse impacts T cell alloimmunity and allows reduction of immunosuppression (IS) after
liver transplantation. Further, chronic and active alcohol abuse impairs regeneration of small liver allografts and
limits the use of a living donor for patients with SAH. We propose that pharmacological mobilization of
endogenous stem cells overcomes the impact of alcohol damage to stem cells and promotes regeneration of
small liver allografts. This treatment could make patients with SAH suitable for transplantation with small livers,
and possibly provide tolerance and freedom from long term immunosuppression. Our proposed studies
involve: 1) evaluating the impact of chronic and active alcohol exposure on allograft rejection and
immunosuppression after LT, 2) determining the effect of chronic and acute alcohol exposure on regeneration
of small liver allografts, and 3) developing a stem cell mobilizing strategy to promote regeneration and
tolerance of small liver allografts in chronic plus binge alcohol feeding rats. The knowledge generated from
these novel studies will improve clinical outcomes by optimizing IS therapy in patients with SAH after ELT,
provide new insights in LDLT for patients with SAH and enable tolerance for the allograft in patients with SAH.

## Key facts

- **NIH application ID:** 9852408
- **Project number:** 5P50AA027054-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** ZHAOLI SUN
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $351,900
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852408

## Citation

> US National Institutes of Health, RePORTER application 9852408, Project 4-Animal transplant models to characterize immune and regenerative effects of alcohol (5P50AA027054-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9852408. Licensed CC0.

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