# Dysfunctional Myelopoiesis and Myeloid-Derived Suppressor Cells in Sepsis Pathobiology

> **NIH NIH RM1** · UNIVERSITY OF FLORIDA · 2021 · $197,253

## Abstract

ABSTRACT
Sepsis remains one of the most catastrophic challenges affecting our adult population. We have argued that
trauma, sepsis and critical illness are diseases of the bone marrow, and represent ‘pathologic activation’ of
myeloid populations. Preferential myelopoiesis and expansion of myeloid-derived suppressor cells (MDSC) are
a hallmark of critical illness, whether due to severe trauma or sepsis. We have spent the past decade
characterizing in bulk both the blood and bone marrow immunological response, as well as the hematopoietic
response in bone marrow. Whole blood transcriptomics and fluorescently-activated cell sorting strategies can
only capture large cohorts of enriched cell populations. Moving forward with these studies requires a more
granular assessment of the function and phenotype of individual stem cell, myeloid and lymphoid cell populations
over time, in patients with differential outcomes to sepsis. For the past decade, we have relied on bulk
transcriptomics using a microarray-based approach originally developed by the Glue Grant using GeneChip™
technology. More recently, we have moved to next generation sequencing (NGS) to obtain both exon-level cell
transcriptomics and epigenetics, as well as plasma histone-bound free-DNA sequences. We are also now
implementing single-cell RNA-seq technologies using a novel second generation multi-omics technology:
Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq). In the program, RM1 GM139690,
Dysfunctional Myelopoiesis and Myeloid-Derived Suppressor Cells in Sepsis Pathobiology, we intend to use
NGS on blood leukocyte and CITE-seq on blood mononuclear cell (PBMC) fractions obtained from 300 sepsis
and trauma patients with different clinical outcomes at multiple time points. Historically, we have relied on either
outside entities (Broad Institute) or UF-shared resources (Interdepartmental Center for Biomedical Research) for
NGS. However, as the need for sequencing requirements has increased substantially secondary to this program
as well as other funded NIGMS-funded programs in the Sepsis and Critical Illness Research Center (SCIRC),
use of a commercial entity or college-wide shared unit is no longer defensible. Not only are we paying higher
costs that include profit and overhead, but high quality, rapid return on analyses has declined with our increases
in volume. Most importantly, our ability to assure rigor and reproducibility as required by NIH is nonexistent with
use of the current outside entities. Here we propose the purchase of an Illumina NextSeq 1000™ sequencer as
a shared-resource within SCIRC to provide NGS (including CITE-seq) to support the RM1 program and other
NIGMS-funded programs in trauma and sepsis. We envision analyzing over 200 samples annually based on the
proposed goals. Additional institutional resources guaranteed from the College of Medicine (COM) will pay the
service contract (~$25k annually) for the life of the grant award(s) and support ...

## Key facts

- **NIH application ID:** 10400260
- **Project number:** 3RM1GM139690-01S1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Philip A Efron
- **Activity code:** RM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $197,253
- **Award type:** 3
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10400260

## Citation

> US National Institutes of Health, RePORTER application 10400260, Dysfunctional Myelopoiesis and Myeloid-Derived Suppressor Cells in Sepsis Pathobiology (3RM1GM139690-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10400260. Licensed CC0.

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