Pannier earns NIH award to enhance gene therapy

University of Nebraska-Lincoln biomedical engineer Angela Pannier has received a 2017 National Institutes of Health Director’s New Innovator Award to develop novel methods that improve use of adult stem cells in gene therapy, a promising tool for treating a variety of diseases.

The honor supports exceptionally creative, early-career researchers pursuing innovative projects with the potential to transform their field of study. Pannier, an associate professor of biological systems engineering, is the first researcher at Nebraska to earn the honor.

“I’m excited to use some new strategies that have never been used in the field before,” Pannier said. “We’ll be able to understand the system on a much bigger scale and move forward into applications.”

Gene therapy is the technique that introduces genetic material into patients’ cells to treat diseases. It has long held promise for tackling a wide variety of medical conditions, including combating cardiac and neurologic diseases, treating genetic disorders and cancer, repairing wounds and improving organ transplant outcomes. But finding effective, safe methods of delivering genes to cells remains a significant hurdle.

Modifying a patient’s own stem cells to incorporate the therapeutic genes is a primary focus. Stem cells have the ability to self-renew and differentiate into many different cell types.

While many efforts look to viruses to introduce therapeutic genes into stem cells, nonviral methods using polymers or other carriers are safer and less likely to provoke an immune response, Pannier said.

But so far, nonviral delivery methods are also less efficient than viruses. Pannier is investigating ways to promote gene uptake by “priming” stem cells – that is, altering them in ways that overcome barriers to incorporating the nonviral gene package.

She’s already had success, discovering that a common steroid drug, a glucocorticoid, markedly improved nonviral gene uptake. The new NIH award will allow her to significantly ramp up her search for other “priming” drugs.

Pannier and her team also will conduct research into better understanding the biological mechanisms of gene delivery, such as why priming drugs affect gene delivery, as well as using mathematical modeling with her collaborator Tadeusz Wysocki, professor of electrical and computer engineering at Nebraska. Understanding the underlying biology will further research into improving priming strategies and delivery methods for nonviral gene therapy.

“Our hope is that we can find a clinically approved drug or combination of drugs that can dramatically improve gene delivery to adult stem cells, and we can then start applying this idea to therapeutic applications,” Pannier said.

Pannier has established an interdisciplinary collaborative network in Nebraska and elsewhere to help expedite promising applications. Collaborators include faculty at Nebraska, including members of the Institute of Agriculture and Natural Resources, University of Nebraska Medical Center and U.S. Meat Animal Research Center.

The five-year award provides nearly $2.2 million in funding and is designed to give early-stage researchers the flexibility to try bold new approaches that could have a major impact on biomedical or behavioral research.

“We are very proud of Dr. Pannier’s pioneering research,” said Archie Clutter, dean of the Agricultural Research Division. “Results of these novel studies will be extremely valuable for use in future tissue engineering and regenerative medicine studies, as well as the delivery of therapeutic proteins, organ transplantation and cancer therapy.”