# Mechanisms of Human Dermal Fibroblast Migration

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $387,750

## Abstract

Summary
This continuation research proposal (in its 12th year) is a total departure from its original title (on
“Mechanism of Human Dermal Fibroblast Motility”), since our discovery of the keratinocyte-secreted form
of heat shock protein-90alpha (Hsp90α) as a potent pro-motility factor and a novel wound healing agent
by our laboratory in 2007 (Li et al, EMBO J). The development of human recombinant Hsp90α protein as a
new treatment for (chronic) diabetic foot ulcers entered its industrial (GMP) phase in 2013 and is under
preparations for clinical trials. During the previous funding cycle of Hsp90α, we established a new pig
wound healing model for burns that recapitulates the clinical characteristics of burn wounds in humans.
Using this model, we have made and reported a new discovery for topically applied Hsp90α to become
potentially the first therapeutic treatment of burn wounds (Bhatia et al, Molecular Therapy, 2016). Here is
the reason why. Burn injuries are different from all other (acute or chronic) types of wounds by going
through an unique event of so-called secondary burn wound progression following the injury, in which a
burn expands both horizontally and vertically from its initial boundary to a larger area within the first 1-2
weeks. Therefore, any effective therapeutics must show dual abilities of 1) preventing the secondary burn
wound progression and 2) thereafter promoting burn wound re-epithelialization (i.e. closure). Currently
there is no FDA-approved therapeutics for burns. We reported that topically applied Hsp90α protein is
such a dual functional therapeutics that promotes burn wound healing. First, Hsp90α prevents the
secondary burn wound progression by protecting the surrounding cells from undergoing heat-induced
Caspase-3 activation and apoptosis. Thereafter, Hsp90α accelerates burn wound healing by stimulating
keratinocyte migration-led re-epithelialization, leading to wound closure. This is the first report for a single
polypeptide that shows such dual therapeutic functions as required for effective treatment of burn wounds.
The goal of this continuation proposal is to elucidate 1) how the secondary burn wound progression takes
place, i.e. necrosis versus apoptosis, and 2) how topical Hsp90α prevents secondary burn wound
progression. Finally, we will establish a new therapeutic entity (NTE), called Fragment-8, of Hsp90α for
drug development. Accomplishment of these preclinical studies will lay the foundation for clinical trials.
1

## Key facts

- **NIH application ID:** 9974521
- **Project number:** 5R01GM067100-16
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Wei Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $387,750
- **Award type:** 5
- **Project period:** 2003-01-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974521

## Citation

> US National Institutes of Health, RePORTER application 9974521, Mechanisms of Human Dermal Fibroblast Migration (5R01GM067100-16). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9974521. Licensed CC0.

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