# Alcohol and tissue injury, from mechanisms to treatments

> **NIH NIH P50** · CLEVELAND CLINIC LERNER COM-CWRU · 2021 · $1,671,407

## Abstract

ABSTRACT
Alcohol abuse is a leading cause of morbidity and mortality worldwide and recent data indicate that alcoholic
liver disease affects over 10 million Americans. In addition to the classically appreciated impact of alcohol use
on the liver, injury to other organs, such as the intestine, skeletal muscle, kidney, adipose tissue and the neural
system contribute to morbidity and mortality associated with chronic alcohol abuse. Understanding both the
common and tissue-specific mechanisms by which ethanol impairs cellular and organ function will lead to the
development of rationally designed therapeutic interventions to both prevent and reverse tissue damage and
disease resulting from chronic alcohol consumption. The overall goal of the Northern Ohio Alcohol Center
(NOAC) is to identify specific molecular targets of ethanol-induced damage, as well as understand the complex
adaptive and maladaptive responses of cells and systems to damage. This information will enable us to 1) target
therapeutic interventions that will either slow and/or reverse the progression of alcohol-induced organ injury and
2) develop biomarkers that reflect injury and will be useful in the future for testing of the efficacy of novel
therapeutic strategies in relevant clinical populations. NOAC brings together an outstanding team of
interdisciplinary investigators and is supported by an Administrative Core, an Animal Models and Cell
Isolation Core, a Clinical Core and a Pilot Projects Core. NOAC utilizes outstanding state-of-the-art facilities at
3 premier research institutions in Cleveland, Cleveland Clinic, Case Western Reserve University and
MetroHealth Hospital, as well as at our ancillary sites at Northeast Ohio Medical University, University of Toledo
and Nationwide Children’s Hospital at the Ohio State University. Four Research Components (RC) are
proposed: RC1 (Brown) investigates the interaction between ethanol, gut microbial metabolites and circadian
clocks and tests “drug-the-bug” strategies to prevent injury, RC2 (Davalos) interrogates the impact of ethanol
activation of microglial cells and neuroinflammation using state-of-the-art live imaging two photon microscopy;
RC3 (Dasarathy) is designed to understand the impact of chronic ethanol on skeletal muscle wasting, a critical
co-morbid feature of alcoholic liver disease and tests the efficacy of targeted nutrients to prevent sarcopenia and
RC4 (Nagy) investigates cell specific mechanisms of hepatocellular death via necroptosis/apoptosis and
develops circulating biomarkers for liver injury. The long-term goal of NOAC is to translate novel findings on
the specific mechanisms by which ethanol disrupts cellular and organ function into effective treatment strategies
for patients with alcoholic tissue injury. Our outstanding investigative team and excellent Core facilities will
continue to work collaboratively to address key mechanistic and translational problems of alcohol-induced tissue
injury, providing unique stren...

## Key facts

- **NIH application ID:** 10056020
- **Project number:** 2P50AA024333-06
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** LAURA E. NAGY
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,671,407
- **Award type:** 2
- **Project period:** 2016-05-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10056020

## Citation

> US National Institutes of Health, RePORTER application 10056020, Alcohol and tissue injury, from mechanisms to treatments (2P50AA024333-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10056020. Licensed CC0.

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