# Mitochondrial regulation of macrophage activation in Chronic Obstructive Pulmonary Disease

> **NIH NIH F30** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $48,471

## Abstract

Project Summary/Abstract
Chronic obstructive pulmonary disease (COPD) is the fourth-leading cause of death in the United States. This
lung disease is primarily associated with cigarette smoke usage and is characterized by damage to lung
epithelium leading to macrophage-driven chronic inflammation, destruction of lung alveoli and airway
thickening. This disease currently has no efficacious treatments and the initiating aberrant cellular pathways
that lead to chronic inflammation in COPD remain unclear. Macrophage metabolism and activation are
intimately linked, and dramatic shifts in metabolism have been observed depending on macrophage
phenotype. Moreover, cigarette smoke is known to change cellular metabolism. The mitochondrial protein,
adenine nucleotide translocase 1 (Ant1), is a critical regulator of cellular metabolism and ATP transport and the
expression of this protein is downregulated in COPD lungs. To study the relationship between immune cellular
metabolism and COPD pathogenesis, I utilize macrophages from Ant1-null mice in a smoke exposure model. I
hypothesize that loss of Ant1 in alveolar macrophages impedes the activation of macrophages in the lung, thus
preventing chronic inflammation that contributes to tissue remodeling and destruction in COPD. My proposal
addresses the following aims: Aim 1: To determine the role of Ant1 in macrophage plasticity and inflammatory
responses due to cigarette smoke. Aim 2: To determine the metabolic mechanisms by which Ant1 modulates
macrophage activation in COPD pathogenesis. Together, these experiments uncover the function of
immunometabolism in basic macrophage biology and in COPD pathogenesis. My proposal includes rigorous
mentored research training with experienced mentors, the support of various collaborators, longitudinal clinical
experience, and professional development pursuits. The scientific, technical, and professional skills gained
during this training period will be critical in my development as an aspiring independent physician scientist
researcher at the forefront of pulmonary immune cell biology.

## Key facts

- **NIH application ID:** 10535966
- **Project number:** 1F30HL165827-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Justin Sui
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $48,471
- **Award type:** 1
- **Project period:** 2022-09-30 → 2024-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10535966

## Citation

> US National Institutes of Health, RePORTER application 10535966, Mitochondrial regulation of macrophage activation in Chronic Obstructive Pulmonary Disease (1F30HL165827-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10535966. Licensed CC0.

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