Research at the Southern Illinois University School of
Medicine brings in $25 million a year in funding but, scientists
say, their efforts are more about hope than about dollars and cents.
Working in laboratories in Springfield and
Carbondale, they seek breakthroughs to ensure lifelong sharp hearing, a
dependable night’s sleep, a life without cancer, and the prevention
of such age-associated disorders as Alzheimer’s disease, heart
disease, and diabetes.
That’s a lot of hope — and a lot to hope
for.
SIU School of Medicine has more than 100 researchers;
seven of them recently told Illinois Times how external funding supports the pursuit of science
and fuels research in the laboratories. They shared hopes and dreams for
their work and visions of a better life for all of us.
Every single day, as part of their mission, SIU
School of Medicine researchers and colleagues in associated hospitals are
among 123 schools of allopathic medicine seeking medical breakthroughs and
innovative approaches to prevention, diagnosis, treatment, and cure.
Of the $25 million annual investment in research at
the SIU School of Medicine, 45 percent comes from competitive awards by
federal sources such as the National Institutes of Health, the Department
of Defense, and the National Science Foundation — federal tax dollars
returning to the community.
Another 20 percent represents competitive grants
awarded by such national foundations as the American Diabetes Association,
the Tinnitus Research Consortium, the Ellison Medical Foundation, and the
American Cancer Society. These dollars come from fundraising campaigns,
walk-a-thons, and private donations. The money, channeled through local,
state, and federal organizations, supports research at the medical school.
Only about 15 of every 100 grant applications
submitted to the NIH result in money for the research studies their authors
propose — so the fact that money ends up in Springfield and
Carbondale attests to the skill and merit of the scientist, as well as to
the quality of the research.
Scientists must first develop and write grant
proposals that describe their ideas and methods of investigation.
Committees of other scientists review and judge the quality of each idea.
This committee of peers decides whether the scientist has the expertise and
requisite resources to complete the research as it’s been proposed.
Only the best scientists and projects actually receive money. The process
is time-consuming, grueling, and highly competitive.
Clinical trials — the ultimate translation of
basic-science research into prevention, treatment, and cure — account
for another 30 percent of SIU School of Medicine research funding. For
patients, these trials, funded mainly by pharmaceutical companies and the
NIH, represent local access to cutting-edge treatments and disease
prevention.
Six of the researchers interviewed by IT have earned national and
international recognition for their work in their specific areas of
biomedical research. The seventh is starting what promises to be an
exciting and successful career worth following.
MARY PAUZA, Ph.D.
Assistant professor, Department of Medical
Microbiology, Immunology, and Cell Biology Research question: What causes type 1 diabetes, and
how can it be treated and prevented? Funding: $628,500 (Juvenile Diabetes Foundation, ADA,
NIH)
The media have given us an appetite for headlines
trumpeting the discovery by some superstar scientist of a novel insight
about a complex disease such as diabetes, but breakthrough discoveries and
real scientific understanding rely on the self-disciplined day-to-day work
of thousands of individual scientists in laboratories around the world.
Pauza focuses her research on type 1, or
insulin-dependent, diabetes. She spends much of her time studying the
T-cell, a kind of lymphocyte (one of several types of white blood cells
found pulsing through our bloodstream along with red blood cells and
platelets). Red cells carry oxygen throughout our bodies, platelets prevent
bleeding, and white cells command our immune systems, fighting foreign
invaders such as infection and triggering autoimmune diseases, among them
type 1 diabetes.
Pauza can describe T-cells in detail, right down to
explaining what each molecule on the surface of the cell does.
In her laboratory, Pauza modifies the function of
T-cells, manipulating the molecules they contain by turning them on and
off. She makes the cells do tricks, first expressing one function and then
another, in a quest to understand why T-cells go awry and help trigger
autoimmune diabetes. She has discovered that when she makes a T-cell
perform one particular kind of trick — turning on molecules that
inhibit their aggressive tendencies — she delays and perhaps even
stops the development of autoimmune diabetes. This is one promising road to
prevention of the disease. Every day in their Springfield laboratory, Pauza
and her team seek to learn how this molecular strategy works to prevent
diabetes.
What drives Pauza? She says she’s
“motivated mainly by a strong desire to uncover new information and
to teach others” and adds, “Work that uncovers new knowledge
that goes against current dogma or existing paradigms is the most exciting
and rewarding.”
ANDRZEJ BARTKE, Ph.D.
Professor of physiology, director of geriatrics
research Research question: How do genetics and caloric
restriction contribute to longer and healthier life? Funding: $9.7 million (NIH, Ellison Medical
Foundation)
Andrzej Bartke has dedicated his research career to
learning just how life goes on . . . and on . . . and on.
Early in his career, Bartke wondered how hormones
triggered reproductive competence — or simply put, fertility and the
drive and desire for sex. Specifically, he discovered that the production
of prolactin, which is turned on by light — in nature, by the length
of the day — leads to heightened levels of male sex hormones,
interest in mating, and therefore reproduction in male hamsters. Bartke
describes the finding as exhilarating, “a feeling of figuring out how
things work, of improving understanding.” He and his team built on
information that was already out there and, he says, were able to
“connect the dots.”
“
This was the first time we could manipulate
the male reproductive activity with the hormone prolactin [and] turn the
whole thing on with just one hormone,” he says.
Ten years or so ago, Bartke made another observation
that has brought him international recognition. “Genetically dwarf
mice live about 50 percent longer than their normal-sized siblings, which
was opposite of what you would expect,” he explains. He found that
the dwarf mice had lower concentrations of three substances — growth
hormone, insulin-like growth factor-1, and insulin — than did normal
mice. Why?
Bartke noted that normal-sized mice fed a nutritious
diet containing fewer calories than their usual diet appeared to live
longer, healthier lives, just like their dwarf counterparts. In 2003, he
was named the recipient of the inaugural Methuselah Mouse Prize for having,
at the time, the longest-lived mouse in the world.
But Bartke’s work is not about just prolonging
life; it’s about understanding and preventing such age-related
conditions as heart disease, type 2 diabetes, and Alzheimer’s
disease. Bartke is adamant that caloric restriction is not malnutrition. In fact, he
says, the experimental diets are carefully prepared to ensure adequate
nutrition, although the total amount of food — and therefore the
calories — is restricted. The animal’s system consequently
becomes insulin-sensitive, and obesity and various age-related diseases are
avoided. Can these findings be applied to human beings? Bartke says,
“If insulin resistance is as bad for people as it is for mice —
and we know that insulin-sensitive mice live longer — it is not too
far an extrapolation to assume that improving insulin sensitivity would
make people younger, live longer, and be more healthy.”
CAROL BAUER, M.D.
Associate professor, Department of Surgery, Division
of Otolaryngology–Head and Neck Surgery
Research question: What causes tinnitus, and how can
it be treated and prevented? Funding: $1.9 million (NIH, Tinnitus Research
Consortium)
If you have tinnitus — ringing in your ears
— you are in famous company. Barbra Streisand ascribes her volatile
temper to the ringing she has been hearing since she was 7, and William
Shatner and Leonard Nimoy each suffer as a result of prop explosions on the
set of the original Star Trek TV series.
Carol Bauer’s research is focused on why
tinnitus occurs and how it ultimately leads to deafness. Bauer explains
that within the cochlea, that spiral portion of the inner ear, are about
10,000 hair cells, “little microphones.” These cells are
constantly searching for sound; when they are damaged in some way, the
brain misses the sound and literally turns up the frequency, or the
“gain,” so high that the affected individual begins to
experience tinnitus.
Bauer and her team have demonstrated that when hair
cells in the cochlea are subjected to overstimulating and damaging sound
— noisy farm equipment, rock concerts, explosions — the hair
cells lie down “like a field of wheat after a tornado,” she
says. Sometimes that damage is temporary, and the hair cells regain their
stance and function. But repeated assaults over time or when the damage is
severe, the condition may intensify and become permanent.
This research has led Bauer and her team to examine
the nerve fibers leading from the hair cells in the cochlea to the brain.
She has found that a drug called gabapentin relieves tinnitus in some but
not all patients. Why? That is one of the many questions Bauer and her team
are asking.
KOUNOSUKE WATABE, Ph.D.
Professor, Department of Medical Microbiology,
Immunology and Cell Biology and Cancer Institute Research question: What is the genetic basis of
preventing cancer cells from metastasizing? Funding: $2.5 million (NIH, National Science
Foundation)
Kounosuke Watabe plays go, an ancient Asian board game that requires discipline and
concentration. Two players — one controlling black stones, one
controlling white — battle to increase the territory they hold and
try to capture the opponent’s stones.
Watabe conveys the same
intensity and clarity of purpose when he talks about his effort to defeat
cancer.
Watabe and his colleagues have identified genes
— specifically, KAI1 and DRG1 — known as metastatic suppressor
genes, that, when present and “turned on,” play a significant
role in containing cancer cells and keeping them from metastasizing.
Metastasis — the spread of cancer from one part of the body to others
— is, Watabe says, the main event leading to death in 95 percent of
the patients with cancer. Watabe and his research team want to figure out
how the genes and the proteins they produce work. They know that when
greater amounts KAI1 protein are present in the body, cancer cells do not
wander from their primary site. This knowledge allows a surgeon to identify
and remove a primary tumor with confidence that the cancer will not recur.
But when the KAI1-regulated protein is present in low amounts, the risk of
metastasis and danger of death are amplified.
Because the KAI1 protein is a factor in all cancers,
it serves as a marker of the risk of metastasis, as well as a target for
therapy and prevention efforts. Watabe and his collaborators have
identified a protein that KAI1 recognizes and binds to. This protein is
expressed on the inner layer of blood vessels. When a cancer cell enters
the bloodstream and sticks to this molecule, the cell dies. Now Watabe,
backed by his team, is “teasing out the players, one by one,”
just as he would construct a strategy on the go board.
The goal, then, is to surround and eliminate the
enemy, the cancer cell, by designing a drug that mimics the protective
protein. Watabe holds out the optimistic guess that this work will take
another three years before a drug similar to the protective protein is
ready for human trials. He has been working on the project since 1996.
SOPHIA RAN, Ph.D.
Assistant professor, Department of Medical
Microbiology, Immunology, and Cell Biology and Cancer Institute Research question: How does a cancer metastasize? Funding: $320,000 (Department of Defense, American
Cancer Society, Penny Severns Breast and Cervical Cancer Research Fund)
In her hours outside the laboratory, Sophia Ran reads
detective stories, admiring flawless logic and loving the surprise of
whodunit. On the job, Ran works to solve a murder mystery of her own,
trying to understand how a tumor grows the blood and lymph vessels that
allow cancer cells to spread throughout the body and form secondary tumors.
“Those guys are the killers,” Ran declares, as emphatically as
if she were Hercule Poirot, solving a crime in an Agatha Christie novel.
On only few occasions do blood and lymphatic vessels
form naturally — within the embryo, within the healing wound, during
the menstrual cycle. The adult organism does not need new blood or lymph
vessels, Ran says, so when new vessels begin to grow in an adult —
for instance, when a cancer invades the body and moves to take over the
system for its own nourishment and survival at the expense of the healthy
body — it is always “a sign of disorder.”
Ran and her colleagues seek to unravel the mystery by
which lymph vessels, in particular, begin to grow in cancerous tumors. They
understand that a complex molecular mechanism induces the pathological
growth. But how? Recent evidence suggests that tumor cells recruit
neighboring lymphatic vessels and stimulate their growth in the malignant
tissue. The lymphatic vessels contain fluid that is naturally designed to
protect normal cells during transport throughout the body. Tumor cells take
advantage of the comfortable transportation offered by the ingrown or
nearby lymphatic vessels: The flow of the lymphatic fluid takes them first
to the local lymph nodes and, from there, to other organs. The best way to
deal with this problem is to keep lymphatic vessels from growing inside a
tumor in the first place. To do that, Ran and her team must figure out
which molecules attract the vessels to the tumor mass and force them to
grow new branches. Better understanding of the process will enable the
development of drugs to prevent it. “
If we can inhibit that, we will lock the tumor
cells into their primary site; we will not let them escape,” Ran
says.Once this
happens, doctors will have a better chance of identifying, isolating, and
removing primary tumors, in effect curing cancer.
JEREMY TURNER, Ph.D.
Assistant professor, Departments of Pharmacology and
Surgery, Division of Otolaryngology–Head and Neck Surgery
Research question: How does the brain change with
age-related hearing loss, and how does hearing loss change the brain? Funding: $150,000 (NIH)
Although new to the game of grant funding, Jeremy
Turner has already received recognition and money for his research focused
on age-related hearing loss. Turner studies the relationship between
hearing loss and changes in the brain: “I look at age-related hearing
loss not so much as an ear problem but as a brain problem.”
Without chemical changes and neurological signals in
the brain, sound would not exist for any of us. As we age and lose hearing
naturally, the hearing part of the brain gets less information from the ear
and itself ages; as a result, we experience less and less of the sound
around us. When, as a result of hearing loss and aging, the hearing part of
our brain doesn’t get its normal input, it begins to atrophy, just
like any muscle that goes unused for too long.
For some of us, this deterioration results in the
need for a hearing aid, but Turner says that fewer than 20 percent of
people who need hearing aids actually use them. By the time an older
individual actually gets a hearing aid, the brain has atrophied to the
point that it has trouble discerning meaningful sound, such as a
spouse’s voice, from background noise. The hearing aid picks up every
sound, makes it louder, and transmits it to the ear. However, at this point
the brain has lost its ability to monitor and winnow important sounds from
meaningless noise. As a result, a person who is wearing a hearing aid for
the first time after an extended period of diminished hearing hears every sound, and the
brain, rusty from disuse, translates the cavalcade of sounds into noise and
nonsense. Turner says that it can take several months to retrain the brain
of an individual new to hearing aids so that the person actually benefits
from them. Most people give up in frustration long before that happens.
Turner’s findings also suggest that if we were
to begin using hearing aids earlier in the aging process, just as our
hearing is beginning to deteriorate, the brain might stay “fit”
and some age-related hearing loss might be avoided. Turner notes that
although people wear glasses without social stigma, the same is not true of
hearing aids. Many people refuse for cosmetic reasons to appear in public
wearing hearing aids, believing that they will be perceived as old or
somehow defective.
A person who loses his or her hearing to age may lose
something more: quality of life. The brain of a person who cannot hear
actually changes, and in some cases the resulting silence is linked to
social withdrawal, isolation, and depression.
LINDA TOTH, Ph.D., D.V.M.
Associate Dean of Research and Faculty Affairs Professor and director, Division of Laboratory Animal
Medicine
Research question: What are the long-term causes of
fatigue and altered sleep pattern in infection?
Funding: $5 million (NIH)
Linda Toth likes to dance the night away — the
cha-cha, the waltz, the tango — but she’s just as passionate
about learning what keeps us awake, or lulls us to sleep, after the party
is over. Chronic fatigue and sleeplessness can impair health and enjoyment
of living.
Toth studies the chemical changes during sleep
deprivation, changes that can be life-threatening. Prolonged sleeplessness
triggers a negative energy balance, impairs the immune system and results
in a gradual deterioration of health leading to infection and even death.
Toth cites two motivations for her work. “One
is the tremendous excitement,” she says, “that comes with
discovering something new about the world of biology and medicine.”
The second “is the hope that I can contribute to finding relief for
the millions of people who suffer from problems with sleeplessness or from
unwanted sleepiness.”
In the near future, Toth believes, scientists will
“unravel much of the basic circuitry in the brain that leads us into
sleeping and waking and will identify genes that influence sleep patterns
or contribute to sleep disorders.” She and her colleagues have
isolated the gene that controls wakefulness and sleeplessness. Now they
want to know how this gene works in the brain and how to control it.
Learning how this gene functions will lay the
groundwork for the development of therapies to permit a good night’s
sleep.
Jane Adrian is a Scottsdale, Ariz.-based freelance
writer in science, health, and education. She is the former clinical
laboratory director at Lincoln Developmental Center and director of the
Clinical Laboratory Science Program at St. John’s Hospital in
Springfield.
This article appears in Sep 29 – Oct 5, 2005.
