# Macrophage Phenotypes and Tissue Repair

> **NIH NIH R35** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $590,382

## Abstract

PROJECT SUMMARY
The long term goals of my laboratory are to generate new insights into the role of the
inflammatory response in tissue repair and to develop novel therapies that shape the
inflammatory response to improve tissue repair. For the past 15 years, the major focus of my
research has been the role of macrophages in tissue damage, repair and regeneration. My
laboratory has published findings that macrophages play important roles in repair of both skin
and skeletal muscle and that these cells display tremendous phenotypic plasticity while helping
to guide a wound through each phase of healing. Our data also demonstrate that macrophage
dysregulation contributes to chronic inflammation and impaired skin wound healing in diabetes
as well as impaired healing of traumatic muscle injuries. Importantly, we have demonstrated and
that targeting macrophages can induce resolution of inflammation and improve healing. For
example, we have found that repurposing the anti-diabetic drug glyburide into a topical
treatment for skin wound healing can be used to inhibit the NLRP3 inflammasome in wounds,
which results in a switch from a destructive pro-inflammatory to a pro-healing macrophage
phenotype and improved healing in diabetic mice. We are now in the process of obtaining an
Investigational New Drug designation for our new formulation that is needed to move forward
into a Phase I human trial on topical glyburide for diabetic leg ulcers. Following this model
pipeline from discovery to clinical trial will be a primary goal of all our future studies.
Despite these advances, much remains to be learned about the plasticity of macrophages
during tissue repair and the factors that regulate macrophage function, including cell-intrinsic
and cell-extrinsic pathways. To this end, my laboratory is studying the contributions of each
developmental stage of the monocyte/macrophage lineage to the regulation of wound
macrophage function during repair of skin and skeletal muscle, in both normal healing and
impaired healing models, in mice and humans. A goal of my laboratory over the next 5 years is
to take advantage of newly developed single cell analysis techniques to determine, using
unbiased methods, the actual phenotypes that macrophages adopt during normal and impaired
wound healing. This approach will help overcome a significant barrier to progress in the field,
which is the widespread use of biased and oversimplistic methods to categorize macrophage
populations in vivo, and has potential to identify novel macrophage populations involved in
healing. We will also use the single cell analysis techniques to guide mechanistic experiments
to elucidate the transcription factors and pathways involved in the regulation of different
macrophage populations. As our research progresses, we plan to address additional significant
gaps in understanding in the wound healing field, including the role of wound pathogens in the
(dys)regulation of macrophage function and tissue repair...

## Key facts

- **NIH application ID:** 9929367
- **Project number:** 1R35GM136228-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** TIMOTHY J KOH
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $590,382
- **Award type:** 1
- **Project period:** 2020-05-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9929367

## Citation

> US National Institutes of Health, RePORTER application 9929367, Macrophage Phenotypes and Tissue Repair (1R35GM136228-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9929367. Licensed CC0.

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