Pakhomov Leads Bioelectrics Research Team Receiving $1.1 million NIH Grant

Cancer-therapy research at Old Dominion University's Frank Reidy Research Center for Bioelectrics has won critical support from the National Institutes of Health (NIH). The funding agency has invested $1.1 million in a project that is led by Andrei Pakhomov, a research associate professor, and is designed to promote human therapeutic applications based upon the center's pioneering work with ultrashort electric pulses.

The project, "Cell Death Induction by High-Voltage, Nanosecond-Duration Electric Pulses (nsEP)," will be funded by NIH for four years beginning July 1. Pakhomov's collaborators on the grant are Juergen Kolb, assistant professor of electrical and computer engineering, and Karl Schoenbach, eminent scholar and Batten Endowed Chair in Bioelectric Engineering.

With the grant, Pakhomov proposes a research agenda that will explore the biological reasons behind the center's remarkable success zapping 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 why the pulses are so effective. Before experimental treatments can evolve into therapeutic applications on humans, this fundamental research on cell function is required.

Preliminary experiments, Pakhomov says, indicate that ultrashort pulses affect cells in ways similar to certain radiation doses and chemical agents-cells die because their DNA, membranes or other components are damaged by free radicals produced by the treatments. (Free radicals are atoms or groups of atoms with an odd number of electrons. Once formed, these highly reactive radicals can start a chain reaction that will damage important cellular parts and perhaps cause cell death.)

One advantage that may come to recommend electrotherapies over conventional cancer therapies is the potential of the pulses to pinpoint tumor cells without causing harm to healthy tissue. Cancer treatments for humans will be advanced significantly if electrotherapy can be shown to work along well-understood pathways, yet without the dreaded side effects that cancer patients experience now from therapies involving chemicals and radiation.

Schoenbach and others researchers at ODU and Eastern Virginia Medical School in the past eight years have garnered worldwide attention for their work with nsEP. Melanoma tumors on the skin of mice have been treated successfully by the researchers, and the base patent for their method is owned jointly by ODU and EVMS.

Electrotherapies against tumor cells have been around for more than three decades, but most involve electric pulses of longer duration that might be described as overkill. Relatively long pulses typically bring on necrosis, a cell death caused by dramatic injury, which can lead to inflammation.

The nsEP employed by the ODU researchers range up to 40,000 volts/cm, but the duration of each pulse is far less than one-millionth of a second. The pulses usually cause no trauma or heat buildup within the targeted cells, and they are able to penetrate the cell membrane before the cell can mount a defense. The effect is subtle, and the orderly death of the cell, called apoptosis, happens over hours, or days, without inflammation.

Pakhomov, who has a doctorate in radiation biology from the Medical Radiology Research Center in Obninsk, Russia, served as a lead scientist at that center. He also was senior scientist with the Army Medical Research Detachment at Brooks Air Force Base in Texas before coming to ODU in 2004. Recently, he has studied changes in cell plasma membranes following exposure to nsEP.

"Andrei's research in electrophysiology is definitely cutting edge, and I am very happy for him and the center that he received such a prestigious grant," said Schoenbach, the founder of ODU's bioelectrics program. "It also shows that our research in bioelectrics is now getting the attention it deserves."

The Bioelectrics Center research team has identified four specific aims of the NIH-funded project: 1) analyze how cell death is dependent upon pulse duration, voltage, number of pulses and other physical parameters; 2) determine how cell cycle phase and growth stage affect sensitivity to nsEP; 3) explore involvement of free radical damage mechanism in cell death caused by nsEP; and 4) analyze mechanisms of long-term disruption of plasma membrane ionic conductance by nsEP and its possible role in nsEP-induced cell death.

Schoenbach, who has been director of the Center for Bioelectrics since it opened in 2004, is turning over the top administrative post in July to Richard Heller, a researcher in electrogenetherapy who is moving to ODU this summer from the University of South Florida College of Medicine.

"It is the first NIH grant obtained by faculty at the Reidy Center," said Schoenbach. "Together with the NIH grants that Richard Heller will bring to ODU, the center will have the highest concentration of NIH funding on campus."