# Molecular mechanisms of post-transplant recurrent alcoholic liver disease

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $349,875

## Abstract

PROJECT SUMMARY
This proposal outlines a plan to investigate the role of ceramide synthase 6 in alcohol-induced lipid droplet
biogenesis and as a potential diagnostic biomarker of pre- and post-liver transplant alcoholic liver disease (ALD)
recurrence. The research will use novel in vitro and in vivo model systems to investigate the hypothesis that
the ceramide synthetic enzyme ceramide synthase 6 (CerS6) regulates alcohol-induced lipid droplet biogenesis
through the transcriptional regulation of the lipid droplet protein, Perilipin 2 (PLIN2). Furthermore, this proposal
will investigate the association between CerS6 upregulation in alcoholic steatosis and its use as an early
biomarker of ALD. The researcher aims 1) to determine the mechanisms by which CerS6 regulates PLIN2
and lipid droplet biogenesis; 2) to determine the effects of hepatocyte-specific CerS6 ablation on lipid
and glucose homeostasis in experimental ALD and 3) To determine if CerS6-ceramides are implicated in
early pre- and post-transplant human ALD. To accomplish these Specific Aims, the researcher proposes to
use genetically engineered mice and human ethanol-metabolizing VL17A cells to perform comprehensive
metabolic phenotyping, lipidomics analyses, and biochemical and functional assays. In addition, the researcher
aims to examine if CerS6 and its ceramide derivatives can be used to diagnose early ALD in both pre- and
recurrent ALD post-transplant. Results of this project will provide evidence for targeting CerS6 as a diagnostic
and therapeutic biomarker in post-transplant ALD recurrence.

## Key facts

- **NIH application ID:** 10823213
- **Project number:** 5R01AA026302-08
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** ROTONYA M CARR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $349,875
- **Award type:** 5
- **Project period:** 2017-09-10 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10823213

## Citation

> US National Institutes of Health, RePORTER application 10823213, Molecular mechanisms of post-transplant recurrent alcoholic liver disease (5R01AA026302-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10823213. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*