# Impact of chronic alcohol consumption on the functional and epigenetic landscapes of monocytes and their progenitors

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2022 · $128,939

## Abstract

SUMMARY
Chronic heavy drinking (CHD) is associated with multiple adverse health outcomes including increased
incidence of liver disease, cardiovascular disease, cancer, and/or infectious disease. Given the increased
incidence of viral, bacterial, and/or fungal infections often seen in patients with CHD, this suggests that alcohol
can have a significant impact on the host immune response and host defense. Several studies have shown
that the most dramatic and consistent changes induced by CHD are evident in the innate immune arm. Using a
non-human primate (NHP) model of voluntary ethanol self-administration, we have reported significant defects
in monocytes/macrophages. CHD is also associated with increased risk for respiratory infection and disease,
notably acute respiratory distress disease syndrome (ARDS). Alveolar macrophages play a critical role in the
inflammatory process associated with ARDS. More recently, we have reported that alveolar macrophages
from CHD macaques exhibit signs of increased oxidative damage, generate an exaggerated inflammatory
response, and dampened anti-bacterial and anti-viral immune responses; thereby providing a link between
CHD and increased incidence of ARDS. However, exact mechanisms remain poorly understood. The purpose
of this diversity supplement is to support Dr. Jamie Sturgill to test the hypothesis that dysregulation of
ceramide levels and signaling in alveolar macrophage with CHD leads to exacerbated inflammatory
responses. Previous work by the Sturgill lab has shown that ceramide is a critical sphingolipid in the lung and
that alterations of ceramide signaling lead to increased reactive oxygen production, macrophage inflammatory
responses, apoptosis, and pulmonary dysfunction. Moreover, ceramide levels are increased in patients with
alcoholic liver disease. Thus, ceramide is a logical target to investigate. This supplement is in line with the
parent R01 that is investigating mechanisms of aberrant inflammation by circulating monocytes. This
supplement will allow Dr. Sturgill to address a critical gap in our knowledge in a focused and mentored project
while honing technical skills and gaining expertise in the field of alcohol and immunity in order to facilitate her
ability to submit an R01 proposal to further interrogate the effects of CHD on pulmonary disease.

## Key facts

- **NIH application ID:** 10616854
- **Project number:** 3R01AA028735-04S2
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Ilhem Messaoudi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $128,939
- **Award type:** 3
- **Project period:** 2021-11-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10616854

## Citation

> US National Institutes of Health, RePORTER application 10616854, Impact of chronic alcohol consumption on the functional and epigenetic landscapes of monocytes and their progenitors (3R01AA028735-04S2). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10616854. Licensed CC0.

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