A researcher at the Keck School of Medicine of USC has shown that a previously unsuspected but common protein in the human body can help skin injuries heal, contradicting decades of conventional wisdom about the biology of tissue repair as well as potential treatments.

The pilot study showed that a natural protein isolated from secretions by injured skin cells, called Heat shock protein 90alpha, significantly improves the healing of wounds on diabetic skin, said principal investigator Wei Li, PhD, a professor in the Department of Dermatology.

This preclinical research, funded by the Southern California Clinical and Translational Sciences Institute (SC CTSI), helped Wei obtain a major new grant from the National Institutes of Health (NIH) to continue the research in larger animals and human subjects.

"The SC CTSI pilot grant allowed us to do innovative and risky things in our experiment design," said Wei. "The data we were able to generate set the stage to convince the NIH to support our larger pre-clinical investigations."

The epidemic of open wounds.

In diabetics, the elderly or others with compromised health, wounds can remain open for months or years, requiring constant and expensive care to hold off infection. Some $10 billion a year is spent annually to provide supportive wound treatment, for diabetic patients alone.

"If a large wound or burn doesn't heal fast, bacteria can get in, expand, and ultimately reach the bone marrow," said Wei. "This can lead to amputations of legs or other limbs, or even jeopardize the patient's life." 

Though familiar enough to everyone who has ever scraped a knee, the skin's ability to repair itself is actually one of the most complicated and mysterious processes in human biology, said Wei. Because the process is incompletely understood, efforts to develop medicines to encourage healing have been largely unsuccessful.

During the last three decades, many experts believed that a family of molecules called growth factor (GF), produced in small amounts in the body, was the primary force in healing. Medicine containing growth factor was developed and approved for use, but its efficacy is modest. In addition, the drug is very expensive and can increase the risk of cancer in patients.

Wei didn't believe growth factors were the missing link in the early and crucial phase of wound healing. His research identified several key limitations for growth factor therapy and demonstrated why GF-based medication failed to help most patients.

It took Wei three years to identify and focus on Hsp90a, which is abundant throughout the body. In fact, cells contain several hundred times more Hsp90a than any other protein.

"No one had a good explanation for why there is so much Hsp90a in every cell, from the top to the bottom of the body," said Wei. "If it's everywhere, we figured it had to have some important purpose – Mother Nature doesn't waste her energy."

Wei believes Hsp90a is instead the driving force to “roof” damaged skin in the early stages of healing by shuttling skin-rebuilding epidermal and dermal cells to the site of a wound.

The research also led to several USC patents in 2012 for new drugs to be based on Hsp90a, currently licensed to an outside pharmaceutical firm for clinical development.

“If Hsp90a could decrease the time of diabetic wound closure from six months to three months, all my 20 years of hard training and work will be worth it,” said Wei.