# Spatial analysis of Alcoholic Hepatitis Liver Tissue

> **NIH NIH R21** · BATTELLE PACIFIC NORTHWEST LABORATORIES · 2021 · $243,755

## Abstract

SUMMARY
Excessive alcohol consumption is a major global public health issue, with alcoholic liver disease (ALD) being a
leading cause of liver-related death in the United States. Alcoholic hepatitis (AH) is a particularly serious form of
ALD with high short term mortality rates, ~35% after one month. Although anti-inflammatory steroid treatments
and other general therapies exist, patient response to such therapies varies widely. There is a need to
understand both the mechanisms of AH disease onset and progression as well as identify markers of treatment
efficacy. To this end, we aim to apply more precise analytical methods to move beyond gross tissue analytics
and towards more cell specific and spatial protein abundances. Specifically, by more precisely analyzing the
spectrum of AH liver tissue, we will gain a better understanding of how hepatocytes progress to apoptotic
ballooning and the effect of these cells on adjacent hepatocytes particularly in moderate or confounded AH
cases. We have developed a breakthrough technology, termed nanoPOTS (Nanodroplet Preparation in One pot
for Trace Samples) which currently enables effective analysis of <10 mammalian cells with extensive proteome
coverage. Coupling nanoPOTS with laser capture microdissection (LCM) and downstream high throughput and
high sensitivity mass spectrometry analysis platforms now enables the technical capability to capture global
protein abundances at the micro scale level. Our objective is to apply nanoPOTS to spatially map with high
resolution heterogenous AH biopsy tissues, guided by histologically defined markers of AH. We hypothesize
that through the analysis of precise intra-liver protein abundance variations, we will gain greater resolution of
protein level mechanisms in the control and dysregulation of the liver in AH. The overall specific aims include
1) Correlate histological events associated with AH pathology, i.e., cell ballooning, steatosis, infiltration, with their
overlapping spatially resolved protein abundances utilizing the LCM-nanoPOTS MS platform. 2) Identify spatial
protein abundance variations across AH, Alcoholic cirrhotic, and normal liver tissues.

## Key facts

- **NIH application ID:** 10261590
- **Project number:** 5R21AA028117-02
- **Recipient organization:** BATTELLE PACIFIC NORTHWEST LABORATORIES
- **Principal Investigator:** Jon Jacobs
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $243,755
- **Award type:** 5
- **Project period:** 2020-09-10 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10261590

## Citation

> US National Institutes of Health, RePORTER application 10261590, Spatial analysis of Alcoholic Hepatitis Liver Tissue (5R21AA028117-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10261590. Licensed CC0.

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