• Breaking the Code
• Nutrition Education vs. Childhood Obesity
• Many States Still Have No Emergency Plan
• Early Screening Is Key in Lymphedema Treatment
• Technology Developed for Cancer Research Finds a New Purpose

Breaking the Code

Mason researchers have targeted HIV and are ready to move in for the kill. New studies uncover information that could end one of the world’s largest health problems.

By Marjorie Musick

In a small lab on Mason’s Prince William Campus, Yuntao Wu and his team of researchers have spent the past six years decoding the molecular processes of the human immunodeficiency virus (HIV). As a result of one of his recent studies, the medical community is one step closer to understanding how HIV, the AIDS virus, attacks cells in the immune system.

“If you ask anyone working on AIDS why they are doing this, they will probably tell you that they want to cure the disease and help people. That is the ultimate goal,” says Wu, assistant professor in Mason’s Department of Molecular and Microbiology. “Once we really comprehend the basic mechanism of how HIV interacts with the body, then it may be possible to target and treat the infection.”

New Inroads in AIDS Research

In the September 2008 issue of the journal Cell, Wu and his collaborators from the National Institutes of Health (NIH) revealed the covert methods that HIV uses to break a barrier present in human CD4 T-cells, the primary immune cells targeted by the virus. HIV-1 infection causes CD4 T-cell depletion, which leads to immunodeficiency and AIDS.

During the six-year study, a team largely comprising research associates and graduate students analyzed CD4 T-cells taken from blood and infected with HIV. The researchers found that when HIV binds to the cell surface, it uses a molecule called chemokine coreceptor CXCR4 to send a signal that activates a cell protein known as cofilin. The protein is then used to cut through the cortical actin cytoskeleton (the circular layer that lies just beneath the cell’s outer membrane).

“Similar to a human skeleton, every cell has a cytoskeletal structure that supports the cell, gives it its shape, and provides a force that allows the cell to migrate. For the virus, this layer also presents a barrier,” says Wu. “We never understood how the virus overcomes this barrier to gain access to the center of the cell. Now we know that HIV triggers the mimicking of a cell process that activates cofilin, which cuts and modifies the cortical actin cytoskeleton and permits the virus to cross it.”

Wu notes that the goal of his research is to attain a fundamental understanding of how the virus interacts with cells and the immune system to identify new ways to treat the disease. Much basic research still needs to be conducted before the findings from this study produce a clinical benefit; however, Wu believes this discovery may later be used to develop a new treatment that could block viral interaction with or viral alteration of the cortical actin cytoskeleton.

“Now we have a basic understanding of the parts that cortical actin and cofilin play in all this. This study really opened avenues for us, and we hope to use this information as a foundation for more detailed studies that could lead to the development of new therapeutic tools,” says Wu.

This research was largely funded by Mason. Additional support was received from the National Institute of Mental Health and the National Institute of Allergy and Infectious Diseases.

From Discovery to Development

Wu estimates that developing a new therapy typically takes 10 years from initial lab work to animal tests and clinical trials—and costs millions of dollars. Wu’s team is pursuing a new treatment based on a Trojan horse concept in which a particle that looks and behaves like the virus is used to target HIV-infected cells. The imposter particles then seek out and infiltrate cells containing a known HIV protein called “Rev.”

“The theory is that once these fake particles identify and invade infected cells, the Rev protein will trigger the release of a toxin that will eliminate the virus’ reservoir,” explains Wu. “So in this sense, it is just like a Trojan horse—it sneaks into the enemy’s territory and then jumps out and attacks.”

What makes Wu’s research unique is his strategy of inducing the decay of HIV-infected T-cells so that patients may stop drug treatment without the virus rebounding.

“Right now, once the patient is put on therapy, it’s a lifetime treatment, arguably, because the current cocktail of drugs only inhibits the virus. Those blocks prevent HIV from spreading, but they are unable to destroy the virus’ resources,” says Wu. “We are trying to develop a new therapy that will reduce the virus’ reservoir so that it will no longer be a living threat to the body.”

The Path to Human Virology

Human disease was not always the subject of Wu’s investigations. He earned a doctorate in virology in 1998 from Queens University in Kingston, Ontario, Canada, after spending four years studying the DNA replication of the baculovirus family— a group of viruses fatal to insects that are often used for nonchemical pest control.

It was not until Wu joined NIH in 1999 that he began examining HIV infection in humans. “After four years of focusing on insect viruses, I really wanted to study human viruses so that I could see my work translated as a benefit to patients,” says Wu. “When I started at NIH, HIV was one of the biggest health threats facing the world, and I thought that maybe I could do something to help fight it.

A widely published researcher whose work has also appeared in prestigious scientific journals such as Science, Journal of Virology, Virology, Retrovirology, and Current HIV Research, Wu believes that a solution to the AIDS epidemic is possible.

“The more we understand the virus, the better we will be able to fight it,” he says. “Every time we discover something new in our lab, we really get excited because it brings us that much closer to finding a cure.”

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Nutrition Education vs. Childhood Obesity

Mason researchers have designed a nutrition education program called “Color My Pyramid” to teach students how to evaluate their dietary intake and activity level. The program incorporates the U.S. Department of Agriculture’s MyPyramid.gov for the Kids Blast-Off Game, a computer game that allows kids to win by fueling their rocket with nutritious foods and a healthy level of physical activity.

More than half of the study participants, ages 9 to 11, were overweight or obese. Analysis showed that the program significantly improved children’s eating habits, increased physical activity levels, lowered blood pressure, and decreased weight and body mass index percentiles.

Lisa Pawloski, co-designer of the program and chair of the Department of Global and Community Health in the College of Health and Human Services, feels confident that childhood obesity can be overcome through education and parental involvement.

“One of the major issues underlying obesity is selecting the right foods,” Pawloski says. “By educating children about making healthy eating choices and educating parents and teachers on how to encourage those behaviors, children may have better success in sustaining a healthy weight.”

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Many States Still Have No Emergency Plan

Seven years after the September 11, 2001 terrorist attacks and in the wake of many major natural disasters, nearly half of U.S. states either have no state-level emergency plan or do not provide it readily to the public, a study by Mason communication professor Carl Botan reveals.

Twenty-two states were unable to provide an emergency operation plan (EOP), withheld the plan on security grounds, or made it difficult for even trained researchers to gain access.

Botan and study co-author Paul Penchalapadu, MA Communication ’08, analyzed the EOPs for three criteria: whether the plans had a two-way communication component, whether they addressed the communication needs of vulnerable populations, and whether they treated public communication as important enough to specifically address it in the plan.

Botan found that out of the 29 jurisdictions that did supply an EOP, 16 of them make explicit or implicit provisions for two-way public communication, such as community forums. Only two plans—Washington, D.C. (which is treated as a state-level entity for this purpose) and New Mexico—received a perfect score of 8 for communication.

“When minutes may make the difference between life and death in an emergency situation, the population should not have to waste precious time looking for answers or whom to turn to,” says Botan.

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Early Screening Is Key in Lymphedema Treatment

Breast cancer patients in fear of developing lymphedema—a potentially painful and disfiguring condition of swelling in the extremities—may be in for some relief.

Researchers found that when physical therapists identified lymphedema in its earliest stages, the condition could be treated effectively.

Lymphedema results from a disruption or blockage of the lymphatic system, which is responsible for transporting lymph fluid and cellular debris. During the five-year study, the team, which included researchers from Mason, the National Naval Medical Center, the University of Michigan-Flint, and the National Institutes of Health, followed breast cancer patients at the National Naval Medical Center in Bethesda, Maryland, from initial diagnosis through treatment and rehabilitation.

Using infrared technology, early stage lymphedema was identified in 43 of the 196 study participants and a light-grade compression bandage was prescribed to those affected. The treatment reduced swelling and alleviated the condition in all of the affected women.

“While more research is needed to confirm these findings, the take-home idea here is that detection depends on sensitive measures,” says Naomi Lynn Gerber, director of the Center for Study of Chronic Illness and Disability at Mason and a coauthor of the study.

Funded by the National Naval Medical Center and the National Institutes of Health, the study appeared in the April 2008 issue of the journal Cancer.

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Technology Developed for Cancer Research Finds a New Purpose

In 2008, Ceres Nanosciences LLLP licensed from Mason a Nanotrap™ technology that was created by world-renowned cancer researchers Emanuel F. Petricoin III and Lance Liotta, codirectors of Mason’s Center for Applied Proteomics and Molecular Medicine.

The technology was used to create the Ceres Nanotrap, a unique nano-size particle capable of trapping, isolating, and preserving the smallest and scarcest of substances in fluid, including blood, urine, and water. Combined with existing diagnostic platforms, it provides a more efficient, reliable, and accurate method for critical diagnostic processes.

Ceres Nanosciences recently announced the use of this technology in a groundbreaking urine test that detects human growth hormone, a compound sometimes used illegally by athletes to boost performance.

Petricoin notes that Mason’s enthusiasm for the commercialization of life science innovations has made it easier to bring his research team’s innovations to the marketplace.

“We’ve received tremendous support at all levels. When we were originally hired, President [Alan] Merten shared his vision of faculty spinning out companies from their inventions. He wanted success stories, he had an appreciation for our background in translational research, and he wanted our discoveries to help the general population,” says Petricoin.