WHAT A YEAR!
Reidy Center Taking Leading Role Worldwide in Bioelectrics Research

Important discoveries and exciting news streamed like a power surge from Old Dominion University’s Frank Reidy Research Center for Bioelectrics during the 2008-09 academic year. But leaders of the facility predict that their best work is still to come.

Major research grants were received, prominent new researchers came on board, new areas of investigation were opened and international media published articles pointing to the leadership role that ODU and its center are playing in developing electric-pulse technology and biological applications of the pulses.

“You can definitely say that we had a good year,” says Richard Heller, the Reidy Center director. “We believe we are hastening the day when bioelectrics realizes its potential in cancer therapies, immunotherapies, vaccine delivery, wound healing and any number of other applications that improve human health and welfare.”

Heller, a pioneer in electrogenetherapy, produced headlines himself during the year, the first coming when he moved from the University of South Florida to ODU and was named director of the Reidy Center. Heller’s wife, Loree, also made the move from USF and is now a researcher affiliated with the center. Florida media labeled their leaving as part of a “brain drain” of researchers seeking better opportunities elsewhere.

Here are some other recent Reidy Center highlights:

• A few months after he came to ODU, Heller and a team of colleagues who did their original investigations in Florida, reported safe and effective treatment of skin cancer in the first-ever human trial of a gene-transfer process assisted by short pulses of electricity. The findings, published by the Journal of Clinical Oncology, show not only regression of treated melanoma skin lesions, but also a secondary effect of in vivo DNA electroporation that in some patients brought about regression of so-called “distant lesions” that had not been treated. This implies a systemic immunological response in the human body to the localized gene transfer. Ultrashort pulses pepper the membranes of target cells, creating entry ways for genetic material. The DNA material that was used is a cytokine that stimulates both adaptive and innate immunity, helping the body to fight cancer.

• The Reidy Center will be the principal provider of services under a $1.6 million contract between ODU and the U.S. Department of Defense during fiscal 2009. ODU is studying new ways for the military to treat wounds. The three approaches that will be part of this study include 1) use of a pulse power device that emits cold plasma to disinfect wounds, 2) use of nanosecond pulsed electric fields that can activate the platelets in blood to promote antibacterial and analgesic results, and 3) delivery of plasmid DNA encoding angiogenic factors by means of in vivo electroporation, which can significantly enhance wound healing as well as enhance the viability of a large flap or skin graft. This electrogenetherapy uses the short pulses to create entry ways for genetic material into cells.

Schoenbach Serves as Spokesman for the New Field of Research

• Karl Schoenbach, the founding director of the six-year-old center who stepped down to focus on research after Heller arrived, was the leading source for an investigative report on bioelectrics during March 2009 in a “Wired” magazine blog on new technology. The researcher took the opportunity to explain the latest research at the Reidy Center, such as the use of special antennae to deliver ultrashort pulses of electricity inside the body to bring about the orderly death of cancer cells. He also touted other methods that he and his colleagues are testing to kill or tweak ­targeted cells—such as tumor cells—with ultrashort pulses without adversely affecting surrounding cells.

• A Reidy Center team led by Associate Professor Andrei Pakhomov began work in 2008 on a $1.1 million project funded by the National Institutes of Health (NIH) and titled “Cell Death Induction by High-Voltage, Nanosecond-Duration Electric Pulses (nsEP).” Pakhomov’s collaborators are Schoenbach and Juergen Kolb, assistant professor of electrical and computer engineering. With the grant, Pakhomov is exploring the biological reasons behind the center’s remarkable success over the last several years at zapping skin tumors on mice. Researchers at the center have a good understanding of the net result of directing ultrashort pulses against cells. Now they want to know precisely why the pulses are so effective.

• Researchers at the Reidy Center are working on a $1.5 million project initiated in 2008 and funded by the NIH titled “Therapeutic Potential of IL-15 Plasmid Delivery to Tumors Using Electroporation.” Heller is the principal investigator and together with other center workers: Shawna Shirley, postdoctoral researcher; Bernadette Marrero, doctoral student; and Cathryn Lundberg, technician, are evaluating a potential therapy for melanoma. This five-year project will develop an appropriate treatment protocol that can eventually be tested in clinical trials for the treatment of melanoma.

• Delivery of genes directly to the heart is also being studied at the Reidy Center. This work was initiated in 2008 following the awarding of a $2.1 million NIH grant titled “Electro Gene Transfer for Coronary Artery Disease.” The Heller-led team includes: Barbara Hargrave, ODU associate professor of biological sciences; Shirley; Dr. John Herre from Eastern Virginia Medical School; and two collaborators from the University of South Florida, Dr. William Marshall Jr. and Dr. Mark Jaroszeski. The study will evaluate the use of pulsed electric fields to deliver plasmid DNA to the heart muscle. The plasmid will encode proteins that can stimulate the formation of new blood vessels.

Gene Delivery Opens New Vistas

• Gene delivery to the skin is the topic of a $1.3 million NIH project titled “Electroporation System for Cutaneous Gene Transfer.” Work on this project started in 2006 while Heller was still at the USF. The grant was transferred to ODU and the Reidy Center early in 2009. It is focused on developing a safe, reliable and effective means of delivering plasmid DNA to the skin. The delivery would be utilized for the delivery of DNA vaccines or plasmids encoding proteins that can be used to treat metabolic disorders. The research team includes the Reidy Center’s Siqi Guo, a postdoctoral researcher; Amy Donate, a doctoral student; and Lundberg, as well as Dr. Jaroszeski from USF.

• Pakhomov is leading another team of researchers at the Reidy Center evaluating the effect of ultrashort pulses on the nervous system. Team members from ODU include James Swanson, professor of biological sciences; Shu Xiao, assistant professor electrical and computer engineering; Stephen Beebe, research professor; Franck Andrei, postdoctoral researcher; Angela Bowman, technician; and Phillip Tan, undergraduate assistant. The study received a $1.85 million grant from the Joint Non-Lethal Weapons Directorate of the Department of Defense and is titled “Comprehensive Study of Neuromuscular Effects of Nanosecond Electrical Pulses.” The major goals of the project are to design, test and assemble appropriate nanosecond pulse generators, to identify neuromuscular effects of nanosecond electric pulses in experimental systems, to explore underlying mechanisms, and to make predictions about neuromuscular disruption and potential health hazards of nanosecond pulse exposure in humans.

• Researchers at the Reidy Center are exploring using ever shorter pulses to direct the electric fields to internal targets without needing to contact the tissue. Xiao is leading this research effort. The team includes Schoenbach, Beebe, Loree Heller, technician Betsy Gregory, doctoral student Thomas Camp and master’s student Mark Migliaccio. The research team is evaluating the use of picoseconds pulses that could be used to detect abnormal cells as well as possibly treat them. The concept is to use antennas to image the dielectric property distribution of a tissue. The transmitting antenna focuses a wideband microwave radiation to scan the targeted tissue. The returned signal carries the information of the dielectric property of the target and is collected by an identical focusing antenna sharing the same focal point as the transmitter and other auxiliary antennas. This modality permits researchers to detect and monitor the pathological changes of tissue (e.g., an early stage cancer) due to the strong contrast of dielectric property existing between normal and diseased tissues.

• Research on biological and chemical effects of pulsed plasma (ionized gas) has been a major component of the bioelectric research activities at the Reidy Center. The plasma team at the center is led by Kolb, with Schoenbach, Xiao, and Ravindra Joshi, University Professor of electrical and computer engineering, as team members. Recent plasma studies have focused on nanosecond plasmas in atmospheric pressure air and in water, and have led to several patents and patent applications. Applications for this research are in chemical decontamination of air, such as decontamination of exhaust gases (“plasma muffler”), and bacterial decontamination of drinking water. Particularly, the research on plasmas in water has found international attention.

Bioelectrics Article Makes Top 10 List

• Schoenbach is the lead author of a research article that made the Top 10 list of the international journal Plasma Sources Science and Technology for 2008. Other ODU authors of the article, “Electrical Breakdown of Water in Microgaps,” are from the Department of Electrical and Computer Engineering: Kolb, Xiao and Joshi. The article reports research results applicable to the construction of a new generation of compact pulse power generators for bioelectric applications.

• Kolb, a young researcher who is taking an ever greater role in Reidy Center investigations, also won praise in December 2008 for an article he authored in the Journal of Physics D: Applied Physics titled “Streamers in Water and Other Dielectric Liquids.” He and co-authors Joshi, Xiao and Schoenbach, presented a fresh look at research promoting improved designs for fast-closing switches for pulsed power systems. Physics D reported that the article had been downloaded more than 250 times within a month after its publication.

• Researchers at the Reidy Center are currently evaluating the antimicrobial activity of cold air plasma jets. Kolb and Loree Heller are combining their expertise to evaluate this approach. The focus of this current study is to examine if the cold plasma jet could be used as a non-chemical method for disinfecting wounds.

• Camp, the doctoral student in electrical engineering at ODU and a researcher at the Reidy Center, received the High Voltage Association Student Excellence Award at the 2008 Institute of Electrical and Electronics Engineers (IEEE) International Power Modulator Conference in Las Vegas. Schoenbach, who is Camp’s adviser, wrote in his nomination letter that Camp “is not only an outstanding student, one of the best I have ever had, but has the potential to become a scientific leader in any field of research that he pursues. Thomas is working on one of our most exciting research programs: the study of high-power, subnanosecond pulsed electric field effects on cells and tissues.”

“It comes down to this,” Heller explains, “the field of bioelectrics is generating more and more interest worldwide, and when researchers want to know more about the electrical engineering, physics and biological sciences that go into bioelectrics they often look to the Reidy Center to find the latest developments.”

Schoenbach, who has been at ODU since 1985 and is an Eminent Scholar, professor of electrical and computer engineering and Batten Endowed Chair in Bioelectrics Engineering, is one of the fathers of bioelectrics. He founded the center with the help of Hampton Roads entrepreneur Frank Reidy and has leveraged expertise both at ODU and at Eastern Virginia Medical School to build the Norfolk facility into a leader in pulsed power science and technology.

Heller’s Arrival Helps Put Center ‘On Top of World’

Beebe and Michael Stacey, two former EVMS professors who had worked with Schoenbach while they were at the medical school, recently joined the ODU faculty and are helping to ramp up cell biology and other biological investigations. Their work, like Pakhomov’s, aims at defining cell and tissue responses to nanosecond pulsed electric fields in order to promote wound healing and cancer control.

Much of the new work at the Reidy Center expands upon a 2006 study by Schoenbach and several colleagues showing that millionth-of-a-second pulses of high-power, but low-energy, electricity will destroy tumor cells and bring complete remission of melanomas on the skin of mice. The electrogenetherapy research of the Hellers opens up new vistas for the center.

“We have done well in the past with utilizing nanosecond electrical pulse technology for biomedical applications, and the Reidy Center has grown substantially over the years,” said Schoenbach. “But now, with Richard and Loree Heller having joined the center, the research scope has broadened and research activities have increased to such an extent that we are on top of the world in the field of bioelectrics. It is exciting to see all these new developments under Richard’s leadership and to be part of them.”

The Reidy Center was a founding member in 2005 of an international research consortium for bioelectrics. Other members are Pulsed Power Science team at Kumamato University, Japan, and the Institute for Pulsed Power and Microwave Technology at the Forschungszentrum, Karlsruhe, Germany. In 2006, the University of Missouri and in 2007, the Institute for Low Temperature Plasma Physics in Greifswald, Germany, joined the consortium. In November 2008, three new full members and one affiliate member were added to the consortium. The new full members are: Center for Molecular Delivery at the University of South Florida; Laboratory of Vectorology and Gene Transfer at the CNRS, Institut Gustave-Roussy and University of Paris XI, Villejuif, France; and IPBS Universite P. Sabatier/CNRS, Toulouse, France. The affiliate member is the German Institute for Food Technology (Deutsches Institut fuer Lebensmitteltechnik e.V.) in Quakenbruek.

“Research at the Reidy Center has seen tremendous growth in the last few years and we are well positioned for future growth,” said Heller. “This growth is fueled by the fact that we have engineers, physicists and biologists working together on projects of common interest. A major area of scientific growth will be based on multidisciplinary teams working together.”

This summer, the center will relocate from Brambleton Avenue to a new facility in Innovation Research Park Building Two in University Village on the east campus. Heller believes the space will enhance research efforts at the center. “The new laboratories are designed to facilitate continued growth of our research programs and provide us with expanded research cores. It is envisioned that these laboratories will enable us to eventually expand the number of researchers within the center. Moving our location to campus will increase our interactions with researchers and students from multiple colleges,” Heller said.