# Acidosis in pulmonary endothelial injury and repair

> **NIH NIH R01** · UNIVERSITY OF SOUTH ALABAMA · 2022 · $385,000

## Abstract

PROJECT SUMMARY/ABSTRACT
The proposed research plan focuses on improving our understanding of the effects of acidosis on pneumonia
and establishing the conceptual basis for diagnostic and therapeutic translation. Acidosis is common in critically
ill pneumonia patients, and is associated with high mortality. The pathophysiology of acidosis in pneumonia is
poorly understood, and current therapies fail to improve major outcomes. Our studies have shown that pulmonary
microvascular endothelial cells (PMVECs) utilize the carbonic anhydrase IX (CA IX) isoform to regulate pH,
metabolism and migration. We also demonstrated that Pseudomonas aeruginosa infection of PMVECs induces
release of cytotoxic amyloid proteins, which disrupts the alveolar capillary membrane. These cytotoxic amyloids
induce soluble CA IX shedding from PMVECs which compromises their repair potential. Based on these
preliminary studies, we test the hypothesis that P. aeruginosa infection induces cytotoxic amyloid production that
leads to shedding of soluble CA IX in PMVECs, increasing lung injury. Specific aims test the hypotheses that: 1)
CA IX is critical to the acid regulation, metabolism and migration of PMVECs and pulmonary endothelial barrier
integrity; and, 2) P. aeruginosa infection elicits cytotoxic amyloid production, causing CA IX shedding in PMVECs,
which increases lung injury. In vitro, we will use genetic approaches and endothelial cell functional assays to
evaluate the effects of acidosis and the role of specific CA IX functional domains during physiologic and infectious
conditions. In vivo and ex vivo, we will use acidosis, pneumonia and isolated lung perfusion mouse models to
translate in vitro findings. Successful completion of this study will provide new insights into the mechanisms
underlying acidosis in pneumonia and help identify CA IX and cytotoxic amyloids as biomarkers and therapeutic
targets for pneumonia.

## Key facts

- **NIH application ID:** 10341493
- **Project number:** 1R01HL160988-01
- **Recipient organization:** UNIVERSITY OF SOUTH ALABAMA
- **Principal Investigator:** Ji Young Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $385,000
- **Award type:** 1
- **Project period:** 2022-02-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10341493

## Citation

> US National Institutes of Health, RePORTER application 10341493, Acidosis in pulmonary endothelial injury and repair (1R01HL160988-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10341493. Licensed CC0.

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