May 23, 2003
Land-grant site suits these health researchers
by Debra Gibson
One of Ann Smiley-Oyen's (standing) research projects looks at how much
Parkinson's patients can improve motor skills through practice. Photo by
Vaclav and Jitka Ourednik quickly established themselves at Harvard
University as noted neuroscientists. Already distinguished in Europe for
their stem cell research, the Ouredniks soon garnered high-profile U.S.
accolades, like the Michael J. Fox/Parkinson's Action Network Young
So, after affiliations with some of the world's most prestigious medical
institutions, the Czech natives decided to establish their own neuroscience
laboratory -- at Iowa State University.
Like dozens of other ISU scientists, the Ouredniks are conducting human
health research on a campus not particularly known for its medical
specialties. Many cite the university's strengths in veterinary medicine,
bioinformatics and plant sciences as their draw to this campus.
"While most stem cell research is being done at universities with medical
schools, we are Ph.D.s, not M.D.s," Vaclav Ourednik said. "We believe stem
cell research needs much more knowledge in how these cells work and
differentiate and react to hosts, and that can be done in any biology
What else can be accomplished at a traditionally non-medical land-grant
university? Take a look.
The brain beat
For more than 10 years, the Ouredniks, both associate professors of
biomedical sciences, have been studying the brain's plasticity and
regeneration, as well as neural transplantation. A diseased or injured brain
has difficulty repairing itself; the use of stem cells from fetal tissue
helps transfer the necessary material into the brain to aid its recovery.
But much is unknown about the stem cells themselves -- how they communicate
with the original brain cells once transplantation occurs, what responses
they may evoke in the host brain, their viability 20 years later.
"[Scientists] promise people we are very close to the miracles that will
heal brain diseases," Jitka Ourednik said. "But I think we are far from
"It's important we slow down a bit from all the media-hyped science and get
back to the basic research into these cells and tissues," her husband added.
Heather Greenlee is a fellow member of the biomedical sciences faculty who
studies stem cells. Trained as a developmental neurobiologist, Greenlee
pursues questions like "How does a neuron decide to become a neuron?" and
"How does it become a specific type of neuron?" She also investigates how
stem-cell related therapies target neurological diseases.
"In patients suffering with Alzheimer's disease," Greenlee explained, "the
amyloid protein is toxic and builds up in the brain. We talk a lot about
stem cell therapy for Alzheimer's patients -- but what happens to those stem
cells when they encounter the toxic proteins? So far, I'm seeing that the
stem cells don't like the amyloids much."
Greenlee also looks at how amyloids affect neurons and photoreceptors (cells
in the eye that sense light). "Most blinding diseases, like macular
degeneration, are a breakdown of the photoreceptors," Greenlee said. "We're
hoping that the eye is another organ that is well-suited for stem cell
One of Greenlee's collaborators is Janice Buss, an associate professor of
biochemistry, biophysics and molecular biology. In addition to their work on
eye-related projects, the scientists have teamed with biomedical sciences
professor Etsuro Uemura to study energy sources in brain cells. In
particular, they are investigating how brain cells that are exposed to the
protein amyloid Β-peptide, or AΒ, lose their ability to take in
glucose, their sole energy source. This breakdown in energy resources may be
an agent in causing Alzheimer's, as the resulting imbalance in the nerve
cells can lead to memory loss and disorientation as the affected neurons
Buss became interested in her specialty when she realized "it was an
opportunity to bring molecular insights into human disease. We have all
kinds of drugs that target molecules, but you first have to understand the
molecules. I want to make the discoveries that enable the people who
ultimately make the drugs."
The Parkinson's pursuit
Parkinson's disease, among the most prevalent of adult neurological
disorders, is another affliction studied by many ISU neuroscientists. The
disease occurs when the portion of the brain that produces dopamine begins
to degenerate. Dopamine is a chemical substance that allows humans to move
smoothly. Parkinson's patients tend to move in a slower, more rigid manner,
and often experience tremors or shakiness.
To better understand the disease, ISU has created the Parkinson's Disorder
Research Program directed by Anumantha Kanthasamy, associate professor of
biomedical sciences. In particular, Kanthasamy, a biochemist and
toxicologist, studies how pesticides may attack and damage brain cells in
the region that is specific to Parkinson's disease.
Though he previously conducted his research at a California medical school,
Kanthasamy looks at ISU as a perfect fit for his studies.
"Because I'm working in an agricultural state, what I do has direct
implications for the people of Iowa," he explained. "Once we know how these
chemicals are killing cells, we can go back and devise strategies to prevent
these diseases and aid in their treatments."
Until the day diseases like Parkinson's are eradicated, scientists like Ann
Smiley-Oyen seeks ways to help patients cope with the symptoms. The
assistant professor of health and human performance studies how two
particular areas of the brain, the basal ganglia and the cerebellum, control
the body's movements.
Specifically, her research looks at how these two brain regions contribute
to motor learning and how intensive practice of repetitive motor skills can
salvage those abilities in Parkinson's patients. Smiley-Oyen conducts a
laboratory project on campus that tests Parkinson's patients on their
abilities to perform such tasks as fastening buttons, intercepting a rolling
ball, aiming toward targets and shifting their weight during controlled
movements (similar to those practiced in tae kwan do). The project aims to
see how much patients can improve skills through practice, and for how long
those skills are retained.
"Medications can help people with Parkinson's," Smiley-Oyen said, "but there
are negative side effects. I'm interested in how we can help improve their
quality of life in ways other than pharmaceutical interventions."
It's all in the delivery
Nonetheless, how drugs are transported to cells is of significant interest
to numerous ISU researchers. For instance, Victor Lin, an assistant
professor of chemistry, works on materials that may deliver chemotherapy
drugs more effectively. Currently, many such medications are delivered
within biodegradable polymers that begin dissolving once they encounter
water in a patient's body. If highly toxic anti-tumor drugs begin leaking
before they reach cancerous cells, they also kill otherwise healthy ones,
leading to such side effects as hair loss.
In Lin's research, the drugs are transported within a material he likens to
"a tiny little sponge ball" that is itself surrounded by a chemical "cap,"
"like a rock that blocks these guys from leaking out," Lin said.
Specific chemicals released only by tumor cells would "unhinge" this cap and
release the drug only into the diseased cells. Long-term, Lin, who received
the National Science Foundation's Early Career Award last year, sees use of
these materials for insulin implants that trigger the drug's release only
when a diabetic's blood sugars reach a certain level.
Surya Mallapragada also is investigating new polymers for insulin delivery,
but was sidetracked by the notion that the same polymers could be used in
gene therapy for cancer patients. An associate professor of chemical
engineering, Mallapragada has redirected some of her efforts to focus on
delivering healthy genes to replace malfunctioning ones.
"Most gene therapy has used modified viruses to deliver the good genes," she
explained. "But viruses could mutate and cause unexpected results. If these
polymers are used, because they are fairly inert, they can hopefully
successfully deliver these genes."
The polymers, which are both pH and temperature sensitive, may also function
someday as "suicide genes" for cancer cells, forcing the damaged cells to
self-destruct, Mallapragada said.
Her husband, Balaji Narasimhan, an assistant professor of chemical
engineering, also investigates more efficient drug delivery systems via
these biodegradable plastics. His research looks at single-dose vaccines
that would administer, in a time-released system, all the drug needed to
prevent diseases like tetanus or diptheria. Such deliveries would eliminate
the need for booster shots and might significantly lower infant mortality
rates in developing countries.
The antigens would be injected into the body encased in tiny spheres,
one-millionth of a meter in diameter. The size and chemistry of these
spheres would control when and how much antigen is released into the
The biomaterials Narasimhan uses have been approved by the U.S. Food and
Drug Administration, but "we are a ways away from using these in human
clinical trials," he said.
Back to basics
The health implications for sound nutrition and effective exercise have
become standard newspaper fare. But long before the topics were trendy,
numerous scientists on campus were studying these basics of longevity.
Diane Birt, for instance, has invested more than a quarter of a century in
the study of dietary prevention of cancer. In particular, she investigates
how plant components can offer protection, and how these components
influence cell division in both normal and cancer cells. Birt, a professor
and chairperson of food science and human nutrition, also heads ISU's Center
for Research on Botanical Dietary Supplements, where studies are under way
on two common herbs, echinacea and St. John's wort.
"I hope we can better define the herbs given to patients in clinical trials
in the future," Birt said, "especially the factors that contribute to the
greatest potential biological activity."
Elsewhere in Birt's department, associate professor D. Lee Alekel is
launching a multi-center clinical trial that will test the effect of soy
isoflavones on bone density in postmenopausal women. Isoflavones are
compounds found in soybeans that behave like estrogen. More than 200 women
in Iowa and California will participate in the three-year trial. Results
from the study may aid in the prevention of osteoporosis, which is a
prevalent consequence of menopause.
Across campus, Paddy Ekkekakis, assistant professor of health and human
performance, is determining how people's emotions affect their ability to
stick with an exercise program. In particular, he studies middle-aged women
who are returning to the gym.
"When previously sedentary individuals first join exercise programs, they
have to deal with negative feelings associated with exertion and fatigue,"
Ekkekakis said. "Professionals have traditionally recommended that they try
not to think about it, think of these feelings as positive, convince
themselves they can accomplish this or slow down when the negative feelings
occur. It remains unknown whether these techniques are effective. We intend
to answer these questions."
In the meantime, ISU researchers are examining how viruses evolve, persist
and change. They are investigating the neurobiology of pain. Scientists are
scrutinizing proteins that may help bodies fight infections, and how the
brain stores memories, and whether exercise strengthens the immune system.
All at a historically non-medical, land-grant institution, with many of
these studies funded by the government's primary agency for medical
research, the National Institutes of Health.
Here's to new traditions.
Ames, Iowa 50011, (515) 294-4111
Published by: University Relations,
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