# Immune and Genetic Controls of Tissue Regeneration in Mice and Humans

> **NIH VA I01** · PHILADELPHIA VA MEDICAL CENTER · 2021 · —

## Abstract

Abstract/Summary
Cutaneous wounds create significant health problems for Veterans, including wartime trauma, diabetic foot
ulcers, pressure ulcers, and pathological scar formation. We aim to devise novel methods to stimulate self-
repair mechanisms and to promote scar-less wound healing/full tissue regeneration in humans. We use a
combination of loss-of-function mouse genetics, parabiosis (where the circulatory systems of two mice are
surgically connected), mass cytometry, flow cytometry, genomics, lineage tracing, and molecular biology to
study ear tissue regeneration in mice. Our prior work and current preliminary data demonstrate that in two
different physiologic contexts, skin-secreted SDF1 regulates the switch between scar formation and tissue
regeneration. In Aim 1, we will study how SDF1 promotes scarring and fibrosis. The canonical receptor for
SDF1 is CXCR4. After injury, we hypothesize that skin-secreted SDF1 recruits CXCR4+ immune cells, which
produce paracrine factors that induce fibroblasts to form fibrous tissue and scar. Recruited cell types will be
defined and functionally tested. In Aim 2, we translate our findings directly into humans. While pathologic scar
formation (keloids and hypertrophic scars) is more common in certain ethnicities, the genetic basis of keloid
formation remains unknown. We hypothesize that increased SDF1 promotes formation of human pathologic
scars. Indeed, human keloid tissue contains higher amounts of SDF1. We propose to identify single nucleotide
polymorphisms in the SDF1 gene of keloid-prone and control patients. Identified polymorphisms will be
introduced and functionally tested in an ex vivo human skin organoid system. This proposal seeks to
understand how SDF1 regulates wound healing and tissue regeneration and to decipher the genetic basis for
pathologic scar formation in humans.

## Key facts

- **NIH application ID:** 10104385
- **Project number:** 5I01RX002701-04
- **Recipient organization:** PHILADELPHIA VA MEDICAL CENTER
- **Principal Investigator:** Thomas H. Leung
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10104385

## Citation

> US National Institutes of Health, RePORTER application 10104385, Immune and Genetic Controls of Tissue Regeneration in Mice and Humans (5I01RX002701-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10104385. Licensed CC0.

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