UChicago researcher sees skin grafts as noninvasive, cost-effective way to treat disease

Scientists at universities can often be found hunkered down in their lab, leaning over a microscope and taking copious notes for their next academic paper. This dedicated research and recording is, of course, incredibly important and admirable work.

However, many scientists are becoming less satisfied with keeping their findings confined to campus communities and scientific journals. Instead, they are working with organizations like Xiaoyang Wu, PhD, associate professor in the Ben May Department for Cancer Research at the University of Chicago, is one such scientist.

“I want to see my research in the lab benefit society and patients,” he said. “That’s really exciting. A lot of scientists want to make an impact from bench to bedside.”

To that end, Wu has been working with the Polsky Center for the past three years to protect his intellectual property and convert his research in epidermal stem cells into widespread applications and treatments of diseases and other ailments. And he is not satisfied with focusing exclusively on skin disorders. Wu sees skin grafts treating everything from diabetes and phenylketonuria (PKU) to hemophilia. He has developed skin grafts that can deliver specific proteins, detect compounds such as insulin in diabetics, and detoxify the blood to rid the body of harmful toxins.

“I think the possibilities are very wide,” Wu said. “There are many things we can do to set up this system, and right now it’s headed in a very interesting direction.”

Non-invasive, long-term and affordable

Wu is researching ways to use genetically modified skin as an engineering platform to provide a solution that naturally releases the proteins needed for treatments into the body on a constant basis. These grafts would be permanent, and regular injections for PKU, hemophilia, and other ailments would no longer be necessary. Wu is currently performing animal trials with mice to test the effectiveness of this treatment, and the success rate has been around 80 percent.

I want to see my research in the lab benefit society and patients. That’s really exciting.

This type of treatment, Wu explains, is noninvasive and offers a long-term, accurate, and continuous solution that is expected to be much more cost-effective than current treatment methods. Viral vectors, for example, is a current mainstream gene therapy to treat rare genetic diseases, but it costs upwards of $2 million. While Wu says he can’t predict specific pricing for skin graft treatments that address some of the same diseases viral vectors focus on, he notes that skin grafts for burn wounds – the most common use of the technique for the past several decades – cost between $3,000 and $5,000.

Wu said that many foundations focused on specific disorders have shown a strong interest in new technologies like his to treat rare diseases like PKU – a genetic disorder that results in the decreased metabolism of a specific amino acid, phenylalanine. If untreated, it often leads to intellectual disability and seizures, among other problems.

“It’s a very long and painful process for the patient and the whole family,” he said. “That was a strong motivation for me to work on something that provides a better alternative. I think we are moving pretty efficiently. We expect clinical trials starting in the next year, and the first indication will be a skin disease because that is the most natural target.”

Treating a multitude of problems with the body's largest organ

Wu sees the treatments he is developing as simple, noninvasive, affordable ways to attack a multitude of problems.

When it comes to diabetes, for example, the skin grafts genetically modified in Wu’s lab can monitor the glucose level in the body and signal changes with a wearable device (such as a smart watch) indicating those levels to the patient. That means diabetics would no longer have to prick their skin with a needle to test the glucose levels in their blood after every meal throughout the day. Working with the Polsky Center, Wu filed a patent application on this technology in 2016 and is working with a partner to bring it to market.

Other interesting potential applications include treatment of obesity and the use of skin grafts to reverse the effects of aging. Modified skin grafts can function as a gene therapy vehicle that Wu has proven can normalize body weight and blood glucose levels in diet-induced obese and diabetic mice.

Wu and his collaborators have already published widely on their efforts. A paper authored and published by Wu in 2017 explains that, “The human skin is a promising conduit for genetic engineering, as it is the largest and most accessible organ.”

“I really think there are many, many possibilities,” he said. “Right now, anything treated with protein replacement therapy, we can create a skin graft to develop a more patient friendly approach to treatment.”

And Wu’s research is not just limited to the use of genetically engineered skin grafts, he is also working with his colleagues at the University of Chicago to use genetic engineering to develop treatment methods for cancer and fibrosis. He sees a bright future for his research, with the potential for various treatments that are simple and much more cost-effective than what is currently available.