# Secondary Analysis of Existing Datasets to Define the Neutrophil Transcriptomic Response to Parenchymal Damage

> **NIH NIH R21** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $124,500

## Abstract

PROJECT SUMMARY/ABSTRACT
Background: Multiple organ failure is associated with a persistent systemic inflammatory response.
Neutrophils, the most abundant leukocytes in blood, are important effectors of this response. Our preliminary
data identified gene expression changes in human neutrophils common to patients with 1) septic shock due to
an intraparenchymal infectious source (such as pneumonia and abdominal abscess); and 2) sterile vasoplegic
shock after major surgery requiring cardiopulmonary bypass. This included increased levels of genes important
for leukocyte extravasation and migration through tissues. Importantly, these changes were not seen in
neutrophils from patients with sepsis from primary bloodstream and urinary tract infections, that is, from
patients without parenchymal injury. Similar changes have been reported in patients after traumatic injury.
Hypothesis: We hypothesize that neutrophils responding to diverse inflammatory insults causing parenchymal
damage display a common, pro-invasive gene expression program.
Methods: In Aim 1, we will use existing whole-transcriptome RNA-seq human neutrophil data from our
laboratory to define the gene expression signature common to septic shock with intraparenchymal source;
multiple organ failure after major surgery; and traumatic injury. Upstream regulators of key gene modules will
be investigated as well as relevant biological pathways. In Aim 2, we will validate the gene expression
signature in secondary analysis of 11 published human neutrophil and leukocyte transcriptome datasets.
These datasets include microarray, bulk RNAseq, and single cell RNAseq data from septic patients with
intraparenchymal versus non-intraparenchymal source, surgical patients, and patients with traumatic injury. In
both Aim 1 and Aim 2, we will compare differences in dynamic expression between patients who developed
multiple organ failure, versus those who recovered without complications.
Expected Results: We expect to identify and validate a targeted neutrophil gene expression program specific
to parenchymal damage; to define the dynamic expression of this program in the development of multiple
organ failure versus good recovery; and to identify candidate upstream regulators for future investigation.
Impact and Long-Term Goals: This study will address current gaps in understanding of the specificity of the
systemic inflammatory response and its relationship to multiple organ failure.

## Key facts

- **NIH application ID:** 10974714
- **Project number:** 1R21HL175493-01
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Anaar Eastoak Siletz
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $124,500
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10974714

## Citation

> US National Institutes of Health, RePORTER application 10974714, Secondary Analysis of Existing Datasets to Define the Neutrophil Transcriptomic Response to Parenchymal Damage (1R21HL175493-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10974714. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*