# High dimensional atlas of circulating neutrophils as reporters of solid organ functional status

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $400,882

## Abstract

High dimensional atlas of circulating neutrophils as reporters of solid organ functional status
 Chronic solid organ diseases (CSODs) collectively account for the majority of deaths in the United
States. A central goal in modern medicine is to improve our ability to predict and detect CSODs in order to
initiate successful therapeutic interventions early or to install appropriate early preventive measures. Several
approaches have been devised to facilitate early detection of disease, including genetic testing and screening
modalities such as imaging and laboratory tests. However, considerable number of CSODs lay silent and
escape even the most watchful clinical eyes, only appearing when it is too late to reverse the pathophysiology
of the disease. The identification of a non-invasive, accessible, sensitive, and comprehensive reporter system
that simultaneously appraises the status of many solid organs would widen the window of opportunity for
therapeutic intervention before overt disease occurs.
 Cellular injury and damage, which precede all organ-based disease, trigger an immune response that
may be transcriptionally encoded into surveilling immune cells. The blood circulation accesses all solid organs
and therefore provides an excellent portal into organ status. Specifically, neutrophils, the most abundant
immune cells in humans, infiltrates nearly all organs under homeostasis. Contrary to their reputation as mere
non-specific anti-microbial combatants, neutrophils have evolved as heterogeneous, functionally versatile cells
that participate in organ homeostasis and mediate CSODs. The advent of high-dimensional approaches such
as single-cell cytometry by time of flight (CyTOF) and single-cell RNA sequencing (scRNA-seq) have revealed
numerous previously unknown neutrophil subpopulations with distinct transcriptional features. Moreover,
tissue-infiltrating neutrophils assume specific organ-defined signatures. Unique from other immune cells,
neutrophils do not establish permanent residence in the tissues they sojourn. This feature coupled with the
neutrophils' short half-life yet significant transcriptional malleability renders them excellent candidates to serve
as sentinels and reporters of organ status. In short, neutrophils that have infiltrated organs potentially return
into the systemic circulation with vital organ-specific codes that may predict homeostatic state compared to
perturbed, diseased states. This proposal will capitalize on these features of neutrophils to create a
comprehensive atlas of their transcriptomics signatures, such that any tissue-specific dysregulation would be
detected as an alteration in these transcriptional signatures. If successful, we envision a clinical world where
blood analysis of neutrophil transcriptomic features would unveil lurking disease far before symptoms develop,
prompting early intervention.

## Key facts

- **NIH application ID:** 10893504
- **Project number:** 5R01ES034235-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Derick Okwan-Duodu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $400,882
- **Award type:** 5
- **Project period:** 2022-04-21 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10893504

## Citation

> US National Institutes of Health, RePORTER application 10893504, High dimensional atlas of circulating neutrophils as reporters of solid organ functional status (5R01ES034235-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10893504. Licensed CC0.

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