Endless Pursuits

/ Discovery / / Kaylyn Christopher / 11.22.16

For UVA Researchers, No Ambition is Too Bold

In popular imagination, world-changing breakthroughs happen in a moment. Isaac Newton watches an apple fall and – thud – humanity understands gravity.

In reality, innovations that change society are preceded by deep questions, big ideas and decades of work. At the University of Virginia, researchers are right now embarking upon explorations that could shape the future.

They are imagining wind turbines that dwarf any in existence and produce 10 times more power. They foresee labs where veterans regrow limbs lost to blast injuries. UVA researchers are creating networks that catalog all the nation’s historical archives in one place. They are looking at how exercise might factor into effective treatments for diseases such as Parkinson’s. And they are bound and determined to end childhood diabetes.

Here is a sampling of just some of the University’s long-range research projects that have the potential to yield very high rewards in the years to come.

What if modern medicine could make it possible for people to regrow limbs? That’s just what Dr. George Christ’s tissue engineering lab at the University of Virginia is seeking to do.

From people who are hurt in car accidents to wounded warriors who have sustained disfiguring and disabling injuries on the battlefield, Christ said the research that his team of undergraduate and graduate students, post-doctoral fellows and research staff is conducting could benefit people who have suffered various levels of trauma.

“We don’t want to give false hope or pretend like we have a solution right now,” Christ said. “But if we can solve military-related injuries caused by things like battlefield explosions, then we can apply those same principles to the civilian population.”

One promising regenerative medicine technology involves creating tissue by prompting stem cells to grow a layer of muscle progenitor cells on a scaffold. The scaffold is then stretched in a bioreactor to mimic muscle movement and is implanted in the subject’s body at a site where a significant amount of muscle has been lost.

“It’s a muscle-repair construct that creates a beneficial regenerative environment that hopefully results in new muscle formation and improved function,” Christ said.

This specific technology is currently being tested on rats, but Christ said a human clinical trial treating patients with cleft lip (a birth defect that results from a lack of tissue in the mouth) is also being planned.

“Can we make enough muscle to reconstitute an arm? Not right now,” Christ said. “But we should move forward with the things we can treat and then scale up. It’s an incremental process.”

According to Christ, interdisciplinary collaboration is essential to the possible success and longevity of his research.

“This is not a problem we can solve on our own. It requires a depth of understanding and a breadth of expertise that goes beyond anybody’s lifetime or resources,” Christ said. “We’re trying to leverage all the talent here at UVA and work with like-minded people around the country and the world to see what we can do to move things forward.”

Christ admits that this endeavor, if successful, could take years, even decades, before patients actually benefit from it. But that possibility of success is enough motivation for him and his team to keep working.

“There’s no metric or recipe for growing a limb, but you shouldn’t give up on the hard stuff because of tight timelines. You have to think long-term and about the big picture,” he said. “Take these soldiers who are 25 years old and have been injured in the line of duty. If there’s a possibility that this research could enable them to walk again when they’re 60, that’s still a pretty big deal.”

UVA has been paving the way toward several breakthroughs in battling Type I diabetes. From identifying common genetic variants that predispose individuals to the disease to creating an artificial pancreas that helps patients control and manage it, a team of doctors and faculty members is striving to make life simpler for individuals who have the condition.

Now, researchers are focusing their collective gaze on curing the disease altogether through the study of beta cells, which are found in the pancreas and are responsible for producing insulin. “In Type 1 diabetes, those cells get destroyed,” said Dr. Richard Shannon, executive vice president for health affairs at the UVA Health System.

According to Shannon, this next step in diabetes research has two aims: to determine how beta cells can be protected from destruction, and to design a way for the beta cells to regenerate once it’s too late.

Shannon said the field of building new beta cells is still very much uncharted territory. Given the University’s track record, however, he believes it is perfectly poised to take on this task.

“UVA has played a fundamental role in identifying risk factors and creating a novel treatment for Type 1 diabetes,” Shannon said. “Now, it embarks on the third phase of the journey, which is to find a cure – something that actually restores the body’s own ability to make insulin.”

Developing a cure for Type 1 diabetes would transform the lives of the nearly 1.5 million people in America who live with the disease, many of whom are children and adolescents.

The artificial pancreas work places UVA at the forefront of streamlining and improving Type 1 diabetes care, said Health System CEO Pamela Sutton-Wallace.

“So it makes sense for us as an institution to take the next step,” she said. “A cure would mean an end to multiple blood sugar checks each day, an end to insulin injections and an end to prescribed treatments, enabling everyone with Type 1 diabetes to live their lives to the fullest.”

The United States lags behind a host of other nations in the amount of energy it derives from renewable sources. Researchers at the University of Virginia want to change that.

Eric Loth, a professor in the School of Engineering and Applied Science, believes the key lies in harvesting wind energy. He’s leading a research project that aims to develop extreme-scale, offshore wind turbines.

“This is a very futuristic concept, not an incremental change,” Loth said. “We’re talking about a completely different way to do wind turbines. We wanted to look to see if it would be possible to have a radical breakthrough that could really reduce the cost of energy, and therefore make wind energy more accessible and more resourceful for the United States.”

Loth said the United States currently has thousands of onshore wind turbines, and the first offshore wind farm was installed off the coast of Rhode Island this year. On average, though, those wind turbines only amount to about one-10th the size of the turbines that Loth wants to design.

“In the U.S., the biggest wind turbines are 6 megawatts,” he said. “Our design would be 50 megawatts, so that’s a lot more powerful than the wind turbines we have today.”

Before that concept can come to fruition, though, Loth said a subscale version of the ultimate 50-megawatt design must be designed and tested.

“The National Renewable Energy Lab is going to allow us to test them on their site,” he said. “This new turbine concept has 20-meter blades and is 12 stories tall,” he said. “And that’s the little one.”

Loth noted that, if everything goes according to plan, it could be nearly a decade before the extreme-scale wind turbines are ready for production and installation, but he added that they would be worth the wait.

“This could be a complete game-changer,” Loth said. “All of a sudden, we could look toward offshore wind as being a real, major renewable energy resource with no carbon emission. That’s a big benefit to the health of our Earth and also our people.”

According to researchers in the UVA Curry School of Education’s Department of Kinesiology, medicine doesn’t always have to come from a pill bottle or be purchased at the drug store.

“We actually think of exercise as medicine,” Kinesiology Professor Steven Malin said. “We are interested in trying to figure out the best dose of exercise to prescribe people.”

The department is focusing its efforts on studying how the prescription of exercise can affect individuals with a variety of disease. In particular, a collaborative project between two UVA kinesiology labs – the Applied Metabolism and Physiology Lab and the Exercise and Sport Injury Lab – as well as UVA’s Department of Neurology and colleagues at the University of Alabama at Birmingham, is trying to determine the effects of physical activity on Parkinson’s disease.

“We’re trying to understand whether patients with Parkinson’s disease could better improve their mobility, metabolic health and cognitive health by doing aerobic exercise or weight lifting,” said Malin, who is also the co-director of the Applied Metabolism and Physiology Lab.

Art Weltman, who chairs the kinesiology department, said the notion of using exercise as a drug is applicable to other ailments, including obesity, cardiovascular disease and diabetes.

For instance, a current study being conducted by researchers in the Applied Metabolism and Physiology Lab is comparing the influence of high-intensity interval exercise versus low, continuous-intensity exercise on blood sugars in patients with pre-diabetes, while a similar study is testing exercise in individuals who are about to undergo bariatric surgery and have metabolic syndrome, a condition that places people at high risk for cardiovascular disease.

According to Weltman, taking a long-term approach to using exercise as medicine has the potential to be life-changing for pre-diabetes patients who make physical activity a part of their normal routine.

“For many patients who exercise on a daily basis and turn their exercise prescription into a lifestyle, metabolic syndrome can go away,” Weltman said. “And that’s better than we can do with any conventional drug that we know about.”

Sorting through archival materials in the name of historical research can be a painstaking process.

“All of it is scattered around in a variety of places,” said Daniel Pitti, associate director for UVA’s Institute for Advanced Technology in the Humanities. “You have to go hunt for something here and something else there, so it all kind of depends on serendipity and following clues and hints to patch together some sense of where everything you want is.”

But Pitti is working to streamline that process. In 2010, Pitti began work on the Social Networks and Archival Context project, which uses computer algorithms to unearth biographical data and records related to various organizations, people and families. The end result is a database that makes millions of archival descriptions available in one place.

Today, the database houses records for 3.7 million different entities – 2.5 million of which are people – that are linked to archival resources. Pitti said the majority of those resources come in the form of correspondences that show whom individuals interacted with, both socially and professionally. Benjamin Franklin’s Social Networks and Archival Context project record, for example, shows traceable connections to approximately 8,000 people.

“It’s basically a historical social network,” Pitti said.

In 2015, the Mellon Foundation awarded Pitti a $1 million grant for the purpose of overhauling the project’s infrastructure.

“We’re going to completely redo the technical infrastructure so that it’ll support the ability to ingest data from external sources and will also let people edit it,” Pitti said.

The grant also allowed for the establishment of a cooperative program, which currently has 17 participating member organizations that turn to the Social Networks and Archival Context project as their primary source for archival descriptions.

Pitti’s hope for the future is that the program will become a sustainable, international resource for anyone who is doing historical research.

“Rather than harvesting this data that is embedded in existing descriptions, we’re trying to get people to create those descriptions separately, and create them here,” he said. “We want to turn it into an ongoing program that will support archival description as it takes place and develop international cooperation.”

According to Pitti, the realization of the Social Networks and Archival Context project could serve generations to come.

“From my perspective this is a public good; it supports international research and education as well as public, life-long learning,” Pitti said. “A lot of archivists have said it’s the future of archival description.”