# S100A9 and MDSC development in sepsis.

> **NIH NIH R35** · EAST TENNESSEE STATE UNIVERSITY · 2020 · $370,000

## Abstract

SUMMARY
The objective of this NIGMS MIRA/R35 proposal is to elucidate how sepsis induces chronically dysregulated
myeloid-derived suppressor cell (MDSC) development, which promotes persistent immunosuppression with
mounting mortality rates. The molecular basis of this newly identified chronic sepsis syndrome is unknown, but
its clinical and economic effects are devastating. This proposal will develop a unifying concept to help explain
delayed immunosuppression and to potentially treat this syndrome of unyielding innate and adaptive immunity
incompetence. It will use an established and validated mouse model in order to develop the working model that
persistent MDSC generation is a key contributor to late/chronic sepsis high morbidity and cumulative high
mortality rate. Preliminary data support the notion that long non-coding RNA Hotairm1 directs S100A9 cytosol
protein into the nucleus, after which it epigenetically generates chronic MDSC-dependent systemic
immunosuppression. Our research plan is designed to identify the signaling and epigenetic reprogramming
network of chronic MDSC generation, using validated biochemical and genetic tools. We expect that targeting
Hotairm1 or S100A9 will overcome sepsis-induced chronic immunosuppression and improve late sepsis
survival. Since targeting molecular mechanisms to treat sepsis has never succeeded in improving mortality
after several decades, our enlightening a new syndrome, a new molecular pathway, and a new molecular
targeting approach will substantially inform major gaps in understanding sepsis-associated life-threatening
inflammation.

## Key facts

- **NIH application ID:** 9904723
- **Project number:** 5R35GM131692-02
- **Recipient organization:** EAST TENNESSEE STATE UNIVERSITY
- **Principal Investigator:** Mohamed A. Elgazzar
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $370,000
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9904723

## Citation

> US National Institutes of Health, RePORTER application 9904723, S100A9 and MDSC development in sepsis. (5R35GM131692-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9904723. Licensed CC0.

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