# Novel Role of Pro-Resolving Lipid Mediators in Signaling Leukocytes

> **NIH NIH F32** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $28,158

## Abstract

Abstract
Uncontrolled inflammation is considered a unifying pathology of a wide range of diseases including sepsis,
cancer, and vascular diseases, among others. Infectious diseases such as sepsis remain an unmet clinical
challenge with high mortality and increasing incidents despite the advances in modern medicine. Phagocytes
play critical role during acute inflammation by controlling host defense mechanisms, via temporal regulation of
classical pro-inflammatory eicosanoids and the production specialized pro-resolving mediators (SPMs) that
include Resolvins, Protecting and Maresins elucidated by the Sponsor and his Laboratory. SPM are sub-
nanomolar potent, stereoselective agonists that promote microbial clearance, containing, and while enhancing
host survival by accelerating resolution mechanisms of inflammation as thus serve as immunoresolvents. The
bone marrow (BM) is a critical organ that generates and mobilizes phagocytes in response to invading
pathogens. This proposal is based on new findings from work in progress, where we identify a specific clusters
of SPM in human BM and BM from mice with remote peritoneal infections, which includes Maresin 1 (MaR1),
Resolvin D1 (RvD1), Resolvin D3, and Lipoxin B4 (LXB4), using state-of-the-art metabololipidomics profiling
approach. To this date, the functional role(s) of SPMs in the bone marrow are uncharted. We proposed to test
the following hypothesis:
Specialized pro-resolving mediators (SPM) produced within the bone marrow during infections at
distant sites, tightly regulate hematopoietic (i.e. myelopoiesis) signals that are required for the
resolution of infectious inflammation and microbial clearance.
To address this following aims are proposed using human BM tissue and murine models of infection. We will
examine: 1) the temporal relationship(s) between SPM and classical pro-inflammatory eicosanoids in BM cells
during local and systemic infections, 2) the functional role(s) of BM Pro-resolving mediators in hematopoietic
cells and 3) cell-specific intracellular signaling circuits of pro-resolving mediators in healthy human BM cells.
The proposed research project, career development and mentorship of Dr. Stephania Libreros by her sponsor
Dr. Charles N. Serhan and the scientific advisory committee would allow her a successful completion of this
proposal. Results from these studies will provide fundamental new insights into the functions of SPMs and
novel pro-resolving pathways in the BM during infection that can help clinicians approach new treatments for
infectious-inflammation by stimulating endogenous resolution mechanisms.

## Key facts

- **NIH application ID:** 9931295
- **Project number:** 5F32HL142175-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Stephania Libreros
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $28,158
- **Award type:** 5
- **Project period:** 2018-06-01 → 2020-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9931295

## Citation

> US National Institutes of Health, RePORTER application 9931295, Novel Role of Pro-Resolving Lipid Mediators in Signaling Leukocytes (5F32HL142175-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9931295. Licensed CC0.

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