# Elucidating the Role of Microbial Community Dynamics in Wound Repair and Regeneration

> **NIH NIH R35** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $374,300

## Abstract

Project Summary
The goal of my research program is to understand the mechanisms underlying how microbial communities
assemble in wound tissue and how these communities influence tissue repair pathways in the skin. During
normal wound healing, the process that leads to tissue regeneration results from a series of tightly regulated
sequential events. In the case of chronic, non-healing wounds, this process is disrupted, leading to a prolonged
inflammatory response and stalled healing. Key recent advances in the understanding of impaired wound healing
is the knowledge that complex microbial communities (a microbiome), exist within the wound tissue. Microbiomes
in the wound tissue do not always cause clinical infection, but it is thought that they might sustain inflammation,
further impairing healing pathways and skin repair. The majority of all published wound microbiome studies
profile the taxonomic composition, but it is unclear how these diverse microbial communities actually interact
with and influence host repair pathways. Thus, the extent of microbial influences on tissue regeneration remains
to be resolved. The skin itself is a diverse ecosystem harboring beneficial microbial symbionts that function to
regulate host immune responses and protect against pathogen colonization. We and others have shown that
chronic wound microbiomes are comprised largely of skin commensals co-existing with skin pathogens and
environmental organisms. This finding suggests that the benefits normally conferred by the skin microbiota may
be lost in a wound environment, and it also highlights our incomplete understanding of how microbial interactions
shape host health.
The proposed research program will define the processes by which structured microbial communities form in
wound tissue and will identify the molecular mechanisms governing inter-species interactions within these
communities. We will accomplish this using a live ex vivo human skin wound model that we have developed to
directly monitor growth dynamics of multi-species consortium and immune responses of resident skin cells. We
can then determine how wound healing pathways shift in response to the makeup of the community and
phenotypic traits, such as formation of microbial biofilm, in a porcine model of wound healing. We will also build
upon our recent discovery that members of the healthy skin microbiota are exceptionally good at inhibiting the
growth of diverse fungi. When placed in an ecological context, this finding is not surprising, as the skin has very
low fungal diversity. However, we have also shown that fungal colonization and interactions with bacteria are
significantly associated with necrosis of wound tissue and delayed healing. We will characterize the metabolites
produced by the healthy skin microbiota mediating competitive interactions with fungi and determine their role in
modulating microbial community dynamics both on healthy skin and within wound microbiomes containing fungi
and bacter...

## Key facts

- **NIH application ID:** 10026417
- **Project number:** 1R35GM137828-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Lindsay Robyn Kalan
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $374,300
- **Award type:** 1
- **Project period:** 2020-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10026417

## Citation

> US National Institutes of Health, RePORTER application 10026417, Elucidating the Role of Microbial Community Dynamics in Wound Repair and Regeneration (1R35GM137828-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10026417. Licensed CC0.

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