# Phospholipidomics and inflammation in sepsis

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $293,550

## Abstract

Project Summary/Abstract
Sepsis remains a major cause of morbidity and mortality. Typically, 50% of all sepsis cases start as an
infection in the lungs. Sepsis is accompanied by multiple organ dysfunction, cytokine storm, and disseminated
coagulation syndrome. These processes directly involve vascular endothelial cells. Although inflammation,
dysregulated coagulation, and alterations in endothelial permeability are recognized factors of septic acute
lung injury (ALI), the endogenous mediators and cellular mechanisms orchestrating processes of endothelial
inflammatory activation and coagulation in septic conditions remain poorly understood. In pilot studies we
identified truncated oxidized phospholipids (TR-OxPLs) in the inflamed lungs using Mass Spectrometry-based
phospholipidomics approach. Our exciting preliminary data show that TR-OxPLs markedly exacerbated lung
dysfunction and impaired vascular endothelial barrier in cell and animal models of septic ALI. Using
pneumonia-related models of ALI induced by live Staphylococcus aureus (S. au, USA300 CA-MRSA clinical
strain 923) or heat-killed S. au (HKSA) this translational study will employ for the first time the quantitative
phospholipidomics approach to identify specific TR-OxPLs elevated during ALI and elucidate their role as
factors exacerbating inflammation and dysregulating coagulation cascade. We hypothesize that increased
generation of TR-OxPLs during sepsis augments lung injury by inducing expression of NLRP3 inflammasome
activator, thioredoxin interacting protein (TXNIP); and by suppressing the expression of vascular anticoagulant,
Tissue Factor Pathway Inhibitor (TFPI). Altogether, these events lead to activation of inflammatory signaling,
dysregulated coagulation, inflammatory cell infiltration in the lung, and organ damage. Aim-1 will determine the
spectrum of TR-OxPL generated in the lungs of S. au-challenged animals. Aim-2 will study the impact of TR-
OxPL generated in S. au-induced septic conditions on the severity of lung injury. Aim-3 will study molecular
mechanisms of TR-OxPL-induced exacerbation of septic inflammation and coagulation. Aim-4 will test new
mechanism-based strategies to alleviate TR-OxPLs generation and their pathologic consequences in S. au-
induced septic ALI.

## Key facts

- **NIH application ID:** 9920760
- **Project number:** 5R01GM122940-04
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Konstantin Birukov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $293,550
- **Award type:** 5
- **Project period:** 2017-07-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9920760

## Citation

> US National Institutes of Health, RePORTER application 9920760, Phospholipidomics and inflammation in sepsis (5R01GM122940-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9920760. Licensed CC0.

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