Rebecca Whelan stumbled across an article on ovarian cancer, she
was shocked to discover that the survival rate for 70 percent of
the women diagnosed with the disease was only 15 to 20 percent.
The article motivated Whelan to begin searching for new, noninvasive
ways to detect the disease in its earliest stages, thereby improving
the outcome of women diagnosed with the deadly cancer.
"Because the initial symptoms are
very subtle, the majority of women with ovarian cancer aren't
diagnosed until the disease has reached stage III and spread from
their ovaries to their upper abdomen," says Whelan, an assistant
professor of chemistry. "If we can find a way to detect this
cancer before it spreads, more women will be able to call themselves
Whelan, who refers to herself as a bio-analytical
chemist, has focused her research on CA 125, a protein that is
often found in higher-than-normal amounts in the blood of women
with ovarian cancer and is widely used as a biomarker to diagnose
the disease. She is spending the summer months in her lab with
four student assistants, searching for new ways to identify the
protein molecule in blood samples and making the identification
process quicker, cheaper, and more reliable than the blood tests
or surgical procedures used by scientists today.
Helping Whelan in the lab are Anita Ofori-Addo '06,
Nolan Pearson '07, Emily Magorian '08, and Matthew
Thayer '08. Each student is experimenting with a different
technique--techniques that may one day be used to screen all women
for ovarian cancer, just like doctors use mammograms to test women
for breast cancer today.
"The detection methods we are working
on combine tools from the fields of analytical chemistry and molecular
biology," Whelan says. "They also take advantage of
the fact that certain biomolecules have the ability to recognize
and bind to specific biomolecules while ignoring all others, which
can help us identify the biomarker protein in serum or blood samples."
Whelan is taking a two-pronged approach
to her searching for a way to detect CA 125 in a blood sample:
she is using an antibody that recognizes the biomarker, and she
is experimenting with aptamers, modified nucleic acid molecules,
as a way to detect CA 125. Both methods exploit the ability of
the antibody or aptamer to "see" CA 125 and ignore
other nearby molecules.
Thayer, a biochemistry and biology major,
is using a small device known as a Spreeta to detect CA 125 in
blood samples. The device uses a process called surface plasmon
resonance (SPR) to recognize CA 125 molecules by measuring the
refractive index of very thin layers of material absorbed onto
a metal surface. Although the Spreeta was not originally designed
for this purpose, Whelan and Thayer are confident that it could
become one of the first hand-held and relatively inexpensive
devices used to identify biomarker molecules in blood samples.
"I never expected to learn as much
as I have already learned, and have yet to learn, this summer,"
says Thayer. "The techniques I'm using in the lab are completely
new to me, and I've had to do a lot of reading to acquaint
myself with them."
But Whelan is hedging her bets and experimenting
with a second method, called capillary electrophoresis, to test
for the presence of CA 125 in blood samples. Pearson, a biochemistry
and piano performance major, is helping Whelan with this project,
which involves using an electric field to separate molecules from
each other in a glass capillary tube. As the molecules drift to
different sides of the tube, Pearson will introduce an antibody
that is attracted to CA 125. This antibody, which is labeled with
a fluorescent dye, will help Whelan and Pearson detect the cancer
biomarker in individual blood samples.
"I'm interested in research
with potential medical applications, so I knew that this project
would be a good match for me," Pearson says. "Plus,
I was attracted to the exciting, maybe even optimistic, big-picture
application of the group's work as a whole."
While antibodies are one way to detect
CA 125, aptamers present a more flexible and less expensive option.
Unlike a naturally occurring antibody or antigen, aptamers are
sytnthetic DNA or RNA molecules that can bind to a particular target
molecule, such as CA 125. But unlike antibodies, aptamers are easier
to obtain and can be used over and over again, under extreme conditions.
Ofori-Addo and Magorian, both biochemistry majors, are making aptamers
using a process known as SELEX -- or Systematic Evolution of Ligands
by Exponential Enrichment -- which involves testing a random pool
of DNA to see which aptamer will grab onto CA 125 and then duplicating
it for future experiments.
"I hope that with a little tweaking,
the work we do this summer will allow doctors to diagnose and treat
a variety of disorders," says Magorian. "I think I
could easily become addicted to developing better methods of helping
people overcome disease."
After agreeing with her lab-mate, Ofori
Addo adds: "As a pre-med student, I'm glad that the
work I'm doing in Professor Whelan's lab will help
make the early detection of ovarian cancer possible. I have no
doubt that this research experience will prepare me to become a
good doctor in the future."
Whelan acknowledges that much of her
research is still experimental, but the goal is worth the effort.
"Anything that can help us avoid major
surgery as a way to diagnose ovarian cancer is going to be easier,
and healthier, for women in the long run," Whelan says. "If
we can improve these techniques, biomarker screening will become
a simple routine test that doctors can perform to diagnose this
disease before it becomes a death sentence for a woman."
Whelan's research is supported by grants from the Camille and Henry
Foundation and the Society for Analytical Chemists (Pittsburgh).