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Studies hold

promise for

Fighting

Disease

By Alyssa Yancey

Breast cancer, which strikes about one of every eight American women, has a five-year survival rate of only 15 percent if diagnosed at an advanced stage. Survival rates improve to nearly 90 percent with early diagnosis, but even the most thorough biopsies can miss cancer during the very early stages.

Arup Neogi

Arup Neogi, professor of physics and member of the Bio/Nano-Photonics research cluster, studies the use of zinc oxide nanoparticles in the detection and treatment of cancer.

Photo by: Michael Clements

Arup Neogi, professor of physics at the University of North Texas, is working as a member of the Bio/Nano-Photonics research cluster on an early cancer detection technique that uses nanoparticles.

"Our method using photonics is more sensitive than current methods," he says. "We would be able to distinguish a single malignant cell from healthy cells."

Neogi's work is just one way UNT researchers are developing tools that could soon revolutionize the healthcare industry. Scientists from fields including biology, chemistry, geography and engineering are working on research that could improve the understanding of the human body and human health, and so lead to better medical treatments and technologies.

Cancer Studies

Neogi's nanomedicine research not only has potential for diagnostic applications, but also may be promising for treatment of cancers and infections.

When cultured with cell samples from cancer patients collected at the University of Texas Medical Branch in Galveston and Northwestern University, the small zinc oxide particles Neogi works with will enter the cancer cells but not the healthy cells. The particles naturally emit light in the presence of infrared light, allowing researchers to quickly identify cancerous cells using non-linear microscopes, which use infrared light to probe deep into tissues.

The presence of malignant cells can be determined just minutes after the culture is created. However, Neogi and his team discovered that if the samples are left for 15 to 20 minutes, the cancer cells can be totally destroyed by the zinc oxide particles.

"We hypothesize that the nanoparticles are antimicrobial in nature and when they break up, they create free radicals that destroy the malignant cells," Neogi says.

"Only the cancerous cells are affected in the tests we've conducted, so we see great potential in using nanoparticles as a cancer treatment that would be less destructive than current treatments that kill both cancerous and healthy cells."

Neogi, whose grants include funding from the National Science Foundation and the Japan Society for Promotion of Sciences, works closely with Shimane University in Matsue, Japan, on the project. He is seeking collaborations with clinical physicians to further develop nanomedicine-based cancer treatments.

His team also is investigating ways to safely deliver the nanoparticles to sites of infection. He says infections contracted in hospitals are an increasing problem.

"Due to the excessive use of antibiotics, many microbes are resistant to drugs," Neogi says. "My team is investigating whether an individual's own blood platelets could be used to penetrate resistant microbes to deliver nanoparticles loaded with drugs directly to the infected site."

If enough funding is secured, Neogi predicts his diagnostic technology could be implemented in labs across the country within two or three years. The treatment element of his research will take longer to be implemented since the materials will need to undergo stringent testing.

Toxicology and Pharmacology

Guenter Gross

Guenter Gross, Regents Professor of biological sciences, was the first to use thin film electrode arrays to record the activity of nerve cell network cultures. The networks are helping researchers test and develop new drugs.

Photo by: Michael Clements

A few blocks from the physics lab where Neogi is investigating the future of cancer treatment, Guenter Gross, Regents Professor of biological sciences, listens to neuronal networks in his lab.

In 1977, Gross and his team were the first researchers in the world to record electrophysiological data from nervous system cell cultures using thin film electrode arrays. He was able to record cellular activity using the small glass plates embedded with microelectrodes and coated with a microscopic layer of tissue.

"Everyone knew you could put electrodes into the brain and measure function, but if you wanted to look at smaller networks of 500 to 1,000 cells, you would destroy the tissue by inserting electrodes," Gross says.

"A single cell doesn't mean that much. It is the group that forms the basic functional unit of the brain, and it is the group dynamics we know the least about. So the idea was, if you cannot bring electrodes to cells, then why not bring the cells to the electrodes."

Originally, Gross thought his new technique would primarily be used to study network theory -- how cells function in groups -- but soon the team discovered additional applications.

"The network theory work is ongoing, but the more practical applications have been for pharmacology and toxicology," Gross says.

"We never expected these networks to behave so similarly to nervous tissues in the body, but they are very representative of the parent organism."

The networks have been used to test antiserums for the military, determine the effectiveness and toxicity of drugs that could slow Alzheimer's disease, and study ways to minimize damage caused by alcohol -- the networks show signs of intoxication at about the same concentrations that humans do.

"The networks on microelectrode arrays are very effective screening platforms that can save time and money during drug development and reduce the number of animals used for this purpose," Gross says.

Kamakshi Gopal and Ernest Moore, professors in the Department of Speech and Hearing Sciences, are collaborating with Gross to assess the potential benefits of various drugs for treating tinnitus, a disorder characterized by ringing in the ears. They also are testing the neurotoxic effects of cisplatin, a commonly used cancer treatment drug known to induce hearing loss and tinnitus, and studying protection against neurotoxicity with antioxidants.

Gross also has been tapped to work on a number of projects for the U.S. Department of Defense.

Most recently, he worked with colleagues at Southern Methodist University, Case Western Reserve University, Vanderbilt University and the University of Texas at Dallas on a multi-million dollar grant aimed at developing next-generation prosthetic limbs.

The researchers investigated optical recording and stimulation techniques to replace less reliable metal electrodes.

Gross conducted toxicity tests on the biosensors that had been developed and studied their effect on neuronal function. The project has concluded, but Gross hopes the team will secure additional funding to further develop more efficient prosthetic interfaces with the nervous system.

Sparking an Interest

Pamela Padilla

Pamela Padilla, associate professor of biological sciences and member of the Developmental Integrative Biology research cluster, is an NSF CAREER award winner investigating human health and disease through the roundworm C. elegans.

Photo by: Michael Clements

Pamela Padilla, an associate professor of biological sciences and a member of UNT's Developmental Integrative Biology research cluster, is investigating human health and disease through the lens of C. elegans, millimeter-long roundworms with insulin-signaling pathways similar to those in humans.

Using an NSF CAREER award, Padilla studies how the worms are able to survive in extremely low oxygen environments. The award, the most prestigious offered by the NSF for young investigators, supports early career development activities of teacher-scholars.

Typically, C. elegans can survive in environments of less than 1 percent oxygen, but recently Padilla and her students discovered the worms can no longer survive in anoxic conditions when fed a diet high in carbohydrates.

She hopes studying mutant C. elegans that are able to survive low-oxygen conditions even when given a high-carbohydrate diet could lead to new treatments for diabetes or oxygen-deprivation related diseases.

Padilla also is using her award to get students interested in research.

"It is difficult to do discovery-based learning in the classroom, especially in large science classes, so many courses end up with recipe-like labs," Padilla says. "My CAREER award included an education component, so I developed a lab module for our genetics course that allows students to do a more open-ended genetic screen."

Undergraduate student Iran Roman took the course last spring and says it opened his eyes to the possibilities of research. Now Roman, who is triple majoring in biology, music theory and German, is working with a graduate student in Padilla's lab to better understand the role of specific genes in glucose processing in C. elegans.

He also is searching for genes that are important in responding to oxygen deprivation with four other undergraduates who became interested in joining the lab after taking the genetics course.

Each year, 300 students take the course, which implements discovery-based learning. The project was profiled in Science magazine in October 2012.

The Tools to Succeed

Successful medical research typically requires a substantial infrastructure. UNT has invested in facilities to advance the capabilities of all of its researchers, including those interested in health.

UNT's Center for Computational Epidemiology and Response Analysis was founded in 2008. The faculty overseeing the center are computer scientist Armin Mikler, medical geographer Joseph Oppong and biologist Sam Atkinson.

Together, they use technologies such as geographic information systems to aid in the prediction and analysis of disease spread in a given population. The center uses computer modeling, simulation and visualization to improve the allocation of public health resources. Researchers affiliated with the center also collaborate with researchers at the UNT Health Science Center.

UNT's Metabolomics and Metabolic Signaling Pathway Research Laboratory, overseen by Vladimir Shulaev, professor of biological sciences, opened last fall.

The lab is one of the top facilities of its kind in the world and will allow researchers to use mass spectrometry and liquid chromatography to analyze the chemical makeup of living organisms.

The university also has recruited faculty experts who can help make sense of the massive amounts of data being produced by the scientific community. Qunfeng Dong, a member of UNT's Computational Chemical Biology and Developmental Integrative Biology research clusters, has a joint appointment in biology and computer science.

Dong works as a bioinformatician, developing algorithms and software to analyze complex data sets such as DNA sequencing information. Through several National Institutes of Health projects, he is collaborating with medical doctors studying bacteria in the human body.

"DNA sequencing and other technologies have revolutionized scientific research, but there have to be tools to comprehend the multitudes of data being produced," Dong says.

"Tools like bioinformatics are helping make groundbreaking medical research possible."

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