# Neutrophil heterogeneity and plasticity in wound healing

> **NIH NIH R35** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $63,665

## Abstract

PROJECT SUMMARY/ABSTRACT
The long-term goal of my research program is to understand neutrophil heterogeneity and functions in diverse
tissues and biomedical contexts. We have combined high-dimensional and single-cell profiling with integrated
bioinformatics approaches to defining context-specific neutrophil landscape. Neutrophils, the most abundant
human immune cell type, play crucial, first-line roles in regulating swift responses against infections and
pathological responses. Emerging evidence has shown that neutrophil response is systematic and context-
specific with distinct phenotypes and functions. Burn injuries are among the most common traumatic injuries
worldwide. In severe cases, patients can die of infection, shock, and/or organ failure, requiring expeditious
clinical responses. Proper wound healing requires a coordinated time-dependent balance of pro- and anti-
inflammatory immune pathways to prevent irreversible systemic damage. Despite being the first to mobilize to
sites of injury, there remains little known about neutrophil heterogeneity, their fates, and which factors control
the plasticity of neutrophils in wound healing. We hypothesize that neutrophils' cellular and molecular landscape
change over time during the wound healing process, and that blood neutrophils could be a marker to predict
complications and outcomes in severe burn injury. To this end, we will focus on two important discoveries in
neutrophil biology over the past decade: (i) neutrophil heterogeneity and adaption to specific tissue environments
revealed by high-dimensional flow cytometry and single-cell transcriptome data and (ii) neutrophil reverse
migration phenotypes, shown in model organisms demonstrating that neutrophils migrate back to the vasculature
in response to inflammation. In this MIRA application, I plan to 1) identify transcriptional and spatial landscapes
of neutrophils and their interactions with other immune cells in human burns using multimodal single-cell profiling
approaches, 2) define reverse migration neutrophil phenotypes in human burns by performing cross-species
single-cell transcriptome analyses of neutrophil heterogeneity in wound healing using clinical samples and pre-
clinical zebrafish burn models, and 3) develop analysis pipelines and methods to predict neutrophil behaviors
defined by imaging using single-cell genomic data in humans and publicly available data from zebrafish and
mouse models. In the next five years, I will establish a research program to study neutrophil heterogeneity and
plasticity in wound healing using multidisciplinary approaches. Our approaches are innovative because we will
employ: (i) state-of-the-art single-cell technologies, (ii) novel integrated bioinformatics method development and
analysis, and (iii) profiling data cross-tissues in humans with in vivo validation models using model organisms.
These studies will generate comprehensive data and provide cellular and molecular landscapes of neutrophil
heter...

## Key facts

- **NIH application ID:** 11034829
- **Project number:** 3R35GM150893-01S1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Huy Quang Dinh
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $63,665
- **Award type:** 3
- **Project period:** 2023-08-05 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11034829

## Citation

> US National Institutes of Health, RePORTER application 11034829, Neutrophil heterogeneity and plasticity in wound healing (3R35GM150893-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11034829. Licensed CC0.

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