# The Roles of LPS-Binding Protein Vascular Peroxidase-1 in Innate Immunity

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $371,250

## Abstract

PROJECT SUMMARY
 Pneumonia is a leading cause of mortality worldwide, affecting approximately 450 million people globally
per year, and results in about 4 million deaths annually. Although the need for research directed toward
development of new antibiotics is urgent, the need to study and better understand host immune responses has
never been greater.
 Our previous studies identified and characterized a new member of animal heme-containing peroxidase
(hPx) family, Vascular peroxidase 1 (VPO1). Like other members of the hPx family, VPO1 generates
hypohalous acids and is able to kill bacteria. Our data show that VPO1-deficient mice have decreased
survival in pneumonia. In addition to its catalytic domains, VPO1 has a unique N-terminus containing five
leucine-rich repeats and four immunoglobulin domains, which bind with high specificity to lipopolysaccharide
(LPS), and kill gram-negative bacteria. Furthermore, our data reveal that LPS causes stronger inflammatory
responses in VPO1-deficient mice; VPO1 can inhibit LPS-mediated activation of Toll-like receptor 4. These
results lead to our central hypothesis that VPO1 has a bifunctional role in innate immunity, both via bactericidal
activities and inhibition of LPS-mediated inflammatory responses. Guided by strong preliminary data, we
propose to pursue three Specific Aims: (1) define the molecular mechanisms of VPO1-mediated bactericidal
activities; (2) evaluate functional roles of VPO1 in regulation of LPS-mediated inflammatory responses; (3)
assess whether exogenous delivery of VPO1 restores host defense function in VPO1-deficient mice.
 Collectively, our proposed research will broadly impact the field by determining and characterizing a new
host defense enzyme, VPO1, with dual function in bacterial killing and reduction of LPS-stimulated
inflammation. These studies will uncover new molecular mechanisms of host-pathogen interaction and
potentially provide a novel (beyond antibiotics) therapeutic strategy of immune-modulation to treat pneumonia
and endotoxin septic shock.

## Key facts

- **NIH application ID:** 9844446
- **Project number:** 5R01AI141724-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Guangjie Cheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $371,250
- **Award type:** 5
- **Project period:** 2019-01-04 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9844446

## Citation

> US National Institutes of Health, RePORTER application 9844446, The Roles of LPS-Binding Protein Vascular Peroxidase-1 in Innate Immunity (5R01AI141724-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9844446. Licensed CC0.

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