A Bridge to Exploration
PURA grants in hand, 45 undergrads move into
the world of research
Whether it's conducting epidemiological studies in a
remote Indian village, constructing artificial cockroach
antennae or playing alongside legendary Scottish folk
musicians, the axiom of learning through doing is what lies
at the heart of the Provost's Undergraduate Research
Awards.
On Thursday, March 10, Steven Knapp, university
provost and senior vice president for academic affairs,
will host the 12th annual PURA Awards ceremony, which will
honor the 45 winners who conducted their projects in the
summer and fall of 2004. Since 1993, about 40 students each
year have received PURA grants of up to $3,000 to conduct
original research, some results of which have been
published in professional journals. The awards, funded
through a donation from the Hodson Trust, are an important
part of the university's mission and its commitment to
research opportunities for undergraduates.
The Provost's Undergraduate Research Awards are open
to students in each of the university's four schools with
full-time undergraduates: the School of Arts and Sciences,
the School of Engineering, the Peabody Conservatory and the
School of Nursing.
The 2005 ceremony will be held in the Glass Pavilion
at Homewood. The entire Hopkins community is invited to the
event, which begins at 3 p.m. with an informal poster
session allowing students to display and talk about their
projects. An awards ceremony hosted by Knapp will begin at
4:30 p.m. and will be followed by a reception. PURA
recipient Robert Whelan will help kick off the ceremony
with a musical presentation on his look into the Shetland
Islands folk tradition.
Whether their awards took them near or far, students
often find the true rewards lie in the journey to
discovery. This year was no different. A sampling of the
winners follows.

BRIDGING ENGINEERING AND ART

CAN A BRIDGE BE STRUCTURAL ART?
Civil engineering major Christina Terpeluk on a Bollman
truss bridge in Savage, Md.
PHOTO BY HIPS/WILL KIRK
|
To most people, a bridge is simply an assembly that
allows travelers to move safely across a river or some
other expanse. But to senior Christina Terpeluk, a
bridge can be a piece of structural art. To qualify, it
must be a work of elegance and efficiency that showcases
its designer's engineering goals in a way that appeals to
the eye.
Supported by a PURA, Terpeluk has spent months
studying 19th-century American iron truss bridges, trying
to determine whether they fit the definition of structural
art, a concept championed by David P. Billington, a civil
engineering scholar at Princeton. For her project, Terpeluk
has conducted detailed studies of three types of truss
bridges built more than a century ago.
The work has required the civil engineering major to
run 21st-century computer programs and pore through fragile
19th-century manuscripts. Beyond the bridges' obvious role
as transportation infrastructure, Terpeluk has explored
their social, economic and symbolic values, trying to
determine what the bridges meant to the communities they
served.
She believes her research is opening new scholarly
terrain. "There has been a lot of 'history of technology'
material written about these bridges," she says. "But there
is almost nothing about the connection between aesthetics
and engineering in them. It surprised me how much I didn't
know."
Structural art, as opposed to fine architecture, has
become an intriguing new field of study, says Sanjay R.
Arwade, assistant professor of civil engineering and
Terpeluk's faculty research sponsor. An architect often
designs pleasing shapes independent of the structural
skeleton of a building, Arwade says. But in a work of
structural art — the Eiffel Tower is a prime example
— the engineering is fully visible, efficiently
designed and aesthetically pleasing in its own right. "A
main idea," he says, "is that you should be able to look at
the structure and 'read' it from an engineering
standpoint."
Terpeluk's affection for bridges dates back to her
freshman year at Johns Hopkins, when an introductory class
required her to build a sturdy model bridge out of
spaghetti strands and glue. She enjoyed the experience so
much that she promptly switched her major from general
engineering to civil engineering.
Later, after taking a course called Perspectives on
the Evolution of Structures, co-taught by Arwade, Terpeluk
decided to apply this standard to 19th-century American
iron truss bridges. Truss bridges use a latticework of
triangles to handle the forces of tension and compression
when a vehicle passes over them. After a long period in
which wooden bridges dominated the American landscape,
19th-century engineers began competing to design more
efficient, less expensive iron truss bridges, primarily for
railroads.
Terpeluk focused on three types of bridge designs
— the Whipple truss, Fink truss and Bollman truss
— and studied examples built in Frederick, Md.;
Hamden, N.J.; and Savage, Md. She used a computer program
to conduct structural analyses of the bridges and employed
traditional research tools to delve into the social,
economic and symbolic background of the structures. "At the
[university's] Peabody Library, I found documents from that
time period focusing on bridge design," she says. "It was
an awesome experience."
In addition, while completing an internship at a
London engineering firm last summer, she was able to visit
a number of truss bridges in the British Isles. That
enabled her to draw comparisons between British and
American bridges from the same period.
Terpeluk hopes to publish her findings in a
peer-reviewed journal or present them at an engineering
conference. "I've learned a lot about doing research," she
says. "It's not an easy task."
After graduating in May, she plans to attend graduate
school and prepare for a career involving the restoration
or rehabilitation of historic structures.
— Phil Sneiderman

PREDICTING HEART FAILURE

PREDICTING HEART FAILURE: Samuel
Hahn with Gordon Tomaselli, professor of medicine, and Fadi
Akar, a research assistant professor in Tomaselli's
lab.
PHOTO BY HIPS/WILL KIRK
|
Samuel Hahn, a senior majoring in biomedical
engineering, has contributed to new research showing that
electrical changes in the heart leading to heart failure
can occur long before a patient exhibits any clinical
symptoms. The initial changes can then spur a second, later
phase of changes that cause lethal heart rhythm
disturbances known as arrhythmias.
The study by Hahn and Fadi G. Akar, a research
assistant professor at the School of Medicine, was the
first to describe the time-course and nature of electrical
abnormalities occurring during the development of heart
failure. A manuscript of their work has been submitted to a
peer-reviewed scientific journal. The two conducted their
research in the laboratory of Gordon F. Tomaselli,
professor of medicine and vice chair for research in the
Department of Medicine.
"By the time most patients are diagnosed with heart
failure, it's too late to really improve their condition,"
Akar says. "By defining the early electrical changes, we
hope to identify new targets for therapy that can either
reverse or, at the very least, hinder the progression of
the vicious cycle of events that ultimately leads to
death."
During heart failure, the pumping action of the heart
becomes inadequate, resulting in a back pressure of blood
along with congestion of the lungs and liver. Nearly 5
million Americans suffer from heart failure, and more than
250,000 die annually from the condition, Hahn says. The
incidence and prevalence of the disease continue to
increase with the aging of the U.S. population.
"Despite remarkable improvements in medical therapy,
the prognosis of patients with heart failure remains very
poor, with almost 20 percent of patients dying within one
year of initial diagnosis and over 80 percent within eight
years," Hahn says. "Of the deaths in patients with heart
failure, up to 50 percent are sudden and unexpected, and
the result of lethal arrhythmias."
For their study, Hahn and Akar isolated samples of
heart tissue about the size of a large postage stamp from
dogs in various stages of heart failure. Next, using a
technique called optical mapping, they stained the tissue
samples with voltage- or calcium-sensitive dyes and shone a
green light on the samples to excite the photosensitive
dyes. The excited photosensitive dyes emitted light in
different amounts depending upon the cellular voltage or
calcium levels in the individual tissue samples. The
emitted light was then collected by a sensitive optical
detection system, converted to current and stored on a
computer for analysis.
Hahn and Akar were able to demonstrate that electrical
disturbances occurred in two distinct phases relative to
mechanical abnormalities. The early changes involved a
delay in the timing of electrical recovery of the heart
muscle following each beat, whereas the later changes
involved the loss of electrical synchrony among various
regions of the heart. The early electrical changes likely
contributed to mechanical abnormalities of the heart, and
the later changes were a consequence of the compromised
mechanical function. The scientists found that both the
early and late changes in the electrical properties were
required to cause a lethal arrhythmia.
"Sam was instrumental in analyzing the data and
helping perform the experiments," says Akar, noting that
their procedure was a two-person job: one to ensure the
health of the heart tissue being studied, and a second to
ensure the performance of all experimental protocols and
the proper acquisition of data by the computer.
"He's been a huge mentor for me," Hahn says of Akar.
"Being an undergraduate, you still have to have direction.
He's given me guidance, freedom and credit."
Tomaselli also praised Hahn for his persistence and
devotion to the project.
"I am often hesitant to take on undergraduate
students, particularly during the most rigorous parts of
their programs, but I made an exception for Sam, and I am
glad that I did," Tomaselli says. "Sam is the type of
student who has the attributes to become a leader in
biomedical research."
After graduating in May, Hahn plans to attend medical
school. "I hope to primarily be a clinical physician," he
says, "but I definitely would love to have the freedom to
pursue questions in medicine that I may have through
research."
— Karen Blum

FIDDLING AROUND IN THE SCOTTISH ISLES

FIDDLING AROUND IN THE SCOTTISH
ISLES: Robbie Whelan spent five weeks last summer in the
Shetland Islands researching their musical folk
tradition.
PHOTO BY HIPS/WILL KIRK
|
History major Robbie Whelan describes the
Shetland Islands as a melting pot of folk tradition. In its
fiddle tunes and dance reels, he says, you can hear the
influences of Irish, American, Scottish, Scandinavian and
seemingly every Anglo culture in the world. But when the
tunes reach these shores, located off the northern coast of
Scotland, they become "Shetlandized."
"The folk songs composed here are defined by a spooky,
northern feel," Whelan says. "They're lively, but hard to
dance to — although somehow people manage it. You
know a Shetland tune when you hear it."
Whelan, a junior, spent five weeks in the Shetland
Islands and two weeks in eastern Scotland researching his
PURA project, titled "Han' Me Doon Da Fiddle: Making Links
Between the Ethnomusicology and Historical Memory of the
Shetland Isles." The project's title was taken from one of
folk legend Tom Anderson's collected musical works, known
as the bible of the Shetland fiddler.
An avid fan of folk music and an accomplished player,
Whelan was in a traditional Irish band in high school that
landed a place in a national competition in Ireland. He
says his parents instilled in him a love of folk, in
particular the traditional music of Ireland and
Scotland.
The Shetlands, known for their ponies and
archaeological sites, consist of about 100 islands, 29 of
which are inhabited. They were occupied by Norse invaders
and colonists after the late ninth century and were annexed
by Scotland in 1472. Whelan spent his days there primarily
in town archives looking for publications penned by folk
culture groups. He also read scores of letters and
newspaper articles, trying to make the case that Shetland
folk music is part of the native peoples' greater identity
in historical terms.
A Writing Seminars minor and the co-arts editor of The
Johns Hopkins News-Letter, Whelan interviewed several of
the islands' elder statesmen of folk: men like Peerie
Willie Johnson and Eric Isbister, who has lived on the
Shetlands' Foula Island all his life. Whelan was also
fortunate enough to play alongside some of the islands'
young musicians at various seaside pubs. At the March 10
PURA ceremony, Whelan will bring photos of some of these
performers, along with a CD featuring excerpts of the 70
hours of music he recorded while on the Shetlands.
For those five weeks, Whelan says he felt a bit like
Sir Walter Scott, referring to the Scottish novelist and
poet. In fact, he says as much in an essay he wrote upon
his return to Baltimore.
"Where he [Walter Scott] was searching for material to
titillate the 19th-century upper classes, I was searching
for fiddle music, its history and its meaning in the modern
world," he wrote. "Our adventures took us to the same
windswept cliffs and beaches, teeming with sea birds, the
same ancient forts, or brochs, and something like the same
firesides in tiny island croft-houses, with tea kettles
hanging from the ceilings and fiddle tunes ringing off of
the walls."
Susan Weiss, who was Whelan's sponsor and his
professor in a medieval and Renaissance course at Peabody,
says that what struck her about Whelan's work was how he
took his interest in Irish pub music and Shetland fiddling
and transformed it into an experience that drew together
many other interests and abilities.
"And by preparing himself in the techniques of
ethnography before he left for the Shetland Isles, he
arrived better able to take advantage of the many
opportunities to interview, record and play together with
local musicians of all ages," says Weiss, a musicologist at
Peabody. "His colorful account reveals someone whose
attitude toward research and investigation has developed in
ways that might not have been possible had he not been
afforded the opportunity provided by the PURA."
— Greg Rienzi

TRIBAL HEALTH IN INDIA

TRIBAL HEALTH: Hari Prabhakar,
seen here in Tamil Nadu, India, studied the success of the
Tribal Health Initiative that brings low-cost care to
remote communities.
PHOTO COURTESY OF HARI
PRABHAKAR
|
Hari Prabhakar's PURA grant helped him learn
more about the health care gap facing tribal people in his
parents' homeland, India. Last summer, he traveled to Tamil
Nadu — the state in which his parents grew up —
to study the success of the Tribal Health Initiative,
started in 1993 to provide low-cost medical care to remote
tribal communities.
The social, political and economic constraints of the
caste system make it difficult for tribal citizens to gain
access to allopathic health services in the rural areas of
their inhabitance, Prabhakar says.
"People in tribes are below the bottom ranks of the
caste system," he says, adding that the disparity between
tribal treatments and those offered by modern medicine are
a cultural hurdle.
Ten percent of India's population is affected, but
it's a problem that isn't widely recognized, he says. An
annual traveler to India, Prabhakar wasn't aware of the
situation until he came across a profile in the Indian
version of Reader's Digest of the two doctors who created
THI. Inspired by their work, Prabhakar wrote to the doctors
to ask if he could visit them to study their program. He
planned a three-month clinical study of THI from an
epidemiological perspective, tracking infant mortality,
genetic disorders, gastrointestinal disorders and
tuberculosis. He found that those numbers have improved
thanks to THI's presence.
The results of the THI infectious diseases study will
be published by the National Medical Journal of India.
While Prabhakar was concentrating on the relative
appearance and magnitude of those four health issues, he
also noticed that the rate of sickle-cell anemia among
tribal people was unexpectedly high. This turn led
Prabhakar to co-author a paper about managing the disease
that has been accepted for publication by the Medical
Anthropology Quarterly and which was presented on Feb. 6 at
the Sickle-Cell Anemia Conference in Wayanad, India, hosted
by the Indian Council of Medical Research and the Swami
Vivekananda Medical Institute.
That Prabhakar discovered something outside his
intended path isn't surprising to his PURA adviser, Veena
Das, chair of the Anthropology Department.
"What has impressed me most about Hari is his
intellectual curiosity along with the ability to work in
very difficult circumstances and to organize interventions
in an effective manner," Das says. "He is able to learn in
new environments, and though he sees complexity, he is not
paralyzed by it."
To supplement his epidemiological study, the
physicians invited Prabhakar to travel with them to remote
villages and observe their treatment of tribal people.
Prabhakar's fluency in Tamil, the predominant language of
the region, was a welcome surprise to the patients.
"The tribal populations of the area are people very
grateful and accepting of the health care interventions
that are offered to them by external sources," says
Prabhakar, a sophomore majoring in public health and the
Writing Seminars.
Writing in an e-mail from India, Regi and Lalitha
George, the couple who started the Tribal Health
Initiative, said, "Hari is a young and very enthusiastic
budding doc — very concerned about the tribals. It is
difficult to find young people like him who are sensitive
to the underprivileged."
— Amy Cowles

LINKING DEPRESSION AND HIGH-RISK
BEHAVIORS

DEPRESSION AND HIGH-RISK
BEHAVIORS: Janet Kuramoto, a public health studies major,
conducted research in the field of HIV/AIDS and injection
drug use.
PHOTO BY HIPS/WILL KIRK
|
Janet Kuramoto said that she often found
herself "starting from scratch" when it came to her
research project.
A junior public health studies major, Kuramoto
conducted research in the field of HIV/AIDS and injection
drug use. Specifically, Kuramoto studied the association
between depressive symptoms and HIV-related risk behavior.
She worked from HIV-prevention studies and surveys
conducted by the lab of Carl Latkin, as associate professor
in the Department of Health Policy and Management at the
Bloomberg School of Public Health.
Kuramoto says that from Latkin's data she was able to
find a significant relationship between the display of
depressive symptoms and high-risk behavior, such as
injection drug use, among urban poor.
The journey to her conclusions, however, was far from
straightforward.
"I wasn't really familiar at all with the area of
injection drug use, and this was the first time I was doing
serious research," she says. "I had to learn a lot about
research methods. These were things I went over in class,
but when I actually had to implement them, I realized I
still had a lot to learn."
Kuramoto says that her mentors were able to help her
turn corners and lead her away from blind alleys with
constructive feedback, whether through face-to-face
meetings or e-mail queries.
"Dr. Latkin and my other mentors were really helpful,
guiding me through my statistical analysis," she says.
"Often I thought I had something, but when it came down to
it, I had to start from scratch. There are so many
variables and limitations to consider when doing this kind
of analysis, you cannot simply make an assertion."
Hope Gilbert, one of Kuramoto's mentors and a research
scientist in the School of Public Health, says that the
young student has produced "stellar" statistical work.
"The most exciting thing that Janet has achieved with
this study was to show statistical differences between the
gender-specific models that she developed to assess the
relationships of HIV [and] drug risk behaviors," Gilbert
says. "She has done great work to address gaps in the
literature that surround gender differences and injection
drug use behaviors."
Gilbert says that Kuramoto gave 100 percent to the
project and challenged herself to step outside the box and
address new issues in the field of HIV/AIDS research among
injection drug users.
"Janet is already an amazing researcher," she says. "I
knew when she proposed her project that she was going to be
an exceptional student, and she has far surpassed my goals
for her this year. She has explored many different models
and biostatistical methods that are used in advanced public
health research, and I am extremely proud of her and of the
work that she has done on this project. I have no doubts
that one day, Janet will make great contributions to the
public health field in her professional career."
— Greg Rienzi

MIMICKING A COCKROACH

LEARNING FROM COCKROACHES: Owen
Loh, working with Brett Kutscher and Noah Cowan, created an
antenna that lets a robot move easily in dangerous
locations.
PHOTO BY HIPS/WILL KIRK
|
Can a robot learn to navigate like a cockroach? To
help researchers find out if a mechanical device can mimic
the pesky insect's behavior, mechanical engineering major
Owen Loh has built a flexible, sensor-laden antenna.
Like a cockroach's own wriggly appendage, the artificial
antenna sends signals to a wheeled robot's electronic
brain, enabling the machine to scurry along walls, turn
corners and avoid obstacles.
The work is important because most robotic vehicles
that are sent into dangerous locations rely on artificial
vision or sonar systems to find a safe path. But robotic
eyes don't operate well in low light, and sonar systems can
be confused by polished surfaces. As an alternative, Noah
J. Cowan, an assistant professor of mechanical engineering,
is turning to the sense of touch, drawing inspiration from
bugs that move quite skillfully through dark rooms with
varied surfaces.
The key, Cowan says, is the cockroach's antennae,
which touch adjacent walls and alert the insect to
obstacles. As a postdoctoral fellow at the University of
California, Berkeley, Cowan collaborated with researchers
at Stanford University to build a crude antenna to show
that a moving machine could use the same technique. After
joining the faculty at Johns Hopkins, he assigned Loh to
build a more complex antenna to permit more advanced
experiments with a cockroach-inspired robot.
In fall 2003, Loh began studying cockroach biology and
working up designs for a robot antenna based on the insect
model. "I liked the idea of combining biology and
robotics," he says.
As a junior last spring, Loh received a PURA that
would allow him to continue this work in Cowan's lab during
the summer. At summer's end, when the lab team quickly
needed an antenna for critical robotic experiments, Loh
assembled a simple but effective prototype in less than a
week.
These experiments resulted in a peer-reviewed paper
that has been accepted for presentation in April at the
International Conference on Robotics and Automation in
Barcelona, Spain. Loh, who is listed as second author on
the paper, plans to attend with Cowan and other members of
the lab team.
In recent months, Loh has fabricated a more advanced
version of the antenna. This model is made of cast
urethane, a flexible rubberlike substance, encased in a
clear plastic sheath. Embedded in the urethane are six
strain gauges — sensors that change resistance as
they are bent. "We've calibrated the antenna so that
certain voltages correspond to certain bending angles that
occur as the antenna touches the wall or some other
object," Loh says.
This data is fed to the robotic's controller, enabling
it to sense its position in relation to the wall and to
maneuver around obstacles. When the antenna signals that
the robot is veering too close to the wall, the controller
steers it away.
The newer version of the antenna is being tested by
Brett Kutscher, a former PURA recipient, who recently
finished his master's degree thesis in Cowan's lab. Cowan
believes the cockroach-inspired antennae being developed by
his team could eventually provide a new generation of
robots with an enhanced ability to move safely through dark
and hazardous locations, such as smoke-filled rooms strewn
with debris.
He says Loh provided crucial assistance. "Owen brought
a set of skills to that lab that none of us had," Cowan
says. "I'm more of an abstract and theoretical researcher.
Owen is very good at making things with his hands."
— Phil Sneiderman

UNDERSTANDING VISUAL INFORMATION

UNDERSTANDING VISUAL INFORMATION:
Chinyere Ogbonna, holding sign, and Melanie Palomares
conducted experiments under sponsor Barbara Landau,
standing.
PHOTO BY HIPS/WILL KIRK
|
Chinyere Ogbonna, a senior majoring in
behavioral biology, is playing an important role in
discovering how genetic differences may influence how human
beings process and understand visual information.
Her original research, focusing on how the brains of
people with a rare genetic disorder called Williams
syndrome perceive visual illusions, was supported by her
PURA.
Ogbonna recognized that people with Williams syndrome
were so spatially impaired that they could not copy simple
patterns as well as the average 6-year-old. Working with
Melanie Palomares, a graduate student in the Department of
Psychological and Brain Sciences, Ogbonna hypothesized that
this was because those with the disorder simply didn't see
the pattern accurately.
Working under sponsor Barbara Landau, the Dick and
Lydia Todd Professor in the Department of Cognitive
Science, Ogbonna and Palomares decided to test this
hypothesis using something called "visual illusions":
simple pen and ink illustrations that attempt to "trick"
the viewer's brain into, for instance, thinking one line is
longer than the other. According to the researchers, such
illusions are crucial evidence that the normal visual brain
sees the world by automatically putting together parts to
make an understandable "whole."
With Palomares' help, Ogbonna showed her visual
illusion cards to several groups of normal people: 3- to
4-year-olds; 5- to 6-year-olds; 7- to 10-year-olds and
adults. She also showed them to people with Williams
syndrome who were between the ages of 10 and 41, with the
average being 19 years old.
"We found that when normal people saw parallel lines
of equal length that are surrounded by 'railroad tracks'
— tilted perpendicular lines — the visual part
of their brain tricked them into thinking that the parallel
lines were not equal in length," Ogbonna says.
Surprisingly, they found that those with Williams
syndrome reacted the same way.
"We were amazed that people with Williams syndrome
tested just like normal adults, which is not what we
expected, based on previous studies of people with this
genetic disorder," Ogbonna says.
Landau, who has studied Williams syndrome for years,
calls Ogbonna and Palomares' results nothing less than
"brilliant."
"The idea of using visual illusions as the test was
just an amazing idea," Landau says. "And the result was
very striking and clear. People with Williams syndrome are
severely impaired spatially. They cannot drive a car. They
are moderately retarded. The fact that they perform on
these tasks the same way that normal, average people do is
remarkable, and has the potential to tell us a great deal
about how we process and understand visual information.
Both Ogbonna and Palomares are brilliant young scientists,
with all of the creativity and motivation needed to be
successful in life. It's really been a privilege to work
with both of them."
— Lisa De Nike

HEART RESEARCH TIMES TWO

HEART RESEARCH TIMES TWO:
Biomedical engineering majors Guarav Gupta and Chris Gregg
conducted separate studies in the lab of Dan
Berkowitz.
PHOTO BY HIPS/WILL KIRK
|
Gaurav Gupta and Chris Gregg, biomedical
engineering majors working in the lab of a medical
researcher, are conducting separate studies that could lead
to improved treatments for heart disease.
Gupta, a sophomore, has found that mice deficient in
the "anti-aging" gene klotho are a good model for
age-related blood vessel stiffening. Gregg, a senior, has
discovered a signaling pathway through which cells regulate
the heart's ability to contract. Both PURA-funded projects
were conducted in the lab of Dan E. Berkowitz, an associate
professor of anesthesiology and critical care medicine in
the School of Medicine with a secondary appointment in
Biomedical Engineering.
Berkowitz praised both Gupta and Gregg for their
diligence and drive. "They were the ones always coming to
me, asking if I'd seen a recent journal article or
suggesting what their next studies should be," he says. "Of
all the students I've mentored, the ones that are
motivated, resourceful and take the most initiative are the
ones that succeed. My role is to focus their energy, like a
lens."
Gupta, who has worked in Berkowitz's lab since his
freshman year, says he likes its congenial atmosphere. With
several undergraduates working there, he says, the students
learn from each other, becoming experts in specific
laboratory techniques.
Gupta studied the cardiovascular biology of aging. In
the aging cardiovascular system, abnormal dilating signals
sent by the chemical nitric oxide, as released by the
endothelial cells lining blood vessels, contribute to
increased risk of heart disease. Among the effects of
impaired endothelial function is an increase in vascular
stiffness, or arteriosclerosis, a contributor to
cardiac-related death.
To study this phenomenon, Gupta compared normal mice
to a population of mice bred to be deficient in klotho, a
gene with "anti-aging" properties. The latter mice exhibit
a syndrome resembling human aging, including vascular
stiffness.
Gupta took blood vessels from the mice and sectioned
them into rings. He then suspended the rings between two
tiny stirrups attached to a machine that measured how
tightly the vessels constricted and recorded the
information on a computer. He then applied different
chemical agents to the rings. He observed a weak response
to acetylcholine, a natural chemical responsible for muscle
contraction, indicating that the endothelial cells were not
working properly and that the signal pathway for nitric
oxide was altered. The appearance of blood vessels in the
klotho-deficient mice was consistent with human aging.
The research could help identify therapeutic targets
for the treatment of age-related dysfunction of the
endothelial cells lining the walls of blood vessels —
a major determinant of vascular disease, Gupta says.
"By discovering the pathway interactions in
age-related endothelial dysfunction, anti-aging therapies
can be developed for the cardiovascular system," Gupta
says. "Not only does this research open new doors for drug
therapy, but it also will allow for further research into
the interaction of cholesterol and vascular stiffness in
conditions such as atherosclerosis and coronary artery
disease."
Gupta plans to build on this work by evaluating the
ability of other medications, such as statins or
cholesterol-lowering drugs, to improve vascular stiffening.
He is applying for funding from the Howard Hughes Medical
Institute.
Gregg, the lab's other PURA recipient, studied the
heart's beta adrenergic receptors. These chemical
messengers are critical for intervening in responses to
physical activity or stress. The receptors also respond to
drugs used to modulate functions such as heart rate.
Disregulation of these receptors and related signaling
pathways is associated with congestive heart failure.
Initially, Gregg studied the ability of the beta-3
receptor to regulate overstimulation to the heart. He
applied to mouse blood vessels an enzyme solution that
released individual heart cells that still functioned as if
they were part of a whole organ. He then exposed the cells
to fluorescent dyes that would reveal under a high-powered
microscope the amount of calcium being released during each
heart beat — a readout of the cells' response to
stimuli. Next, he applied to the cells agents that either
stimulate or inhibit specific proteins to disrupt signal
pathways involved in contraction.
Along the way, he found a pathway related to the
beta-2 receptor whereby stimuli regulate the heart's
ability to contract. The knowledge could eventually lead to
better treatments for heart failure, Berkowitz says.
Gregg presented his research results March 6 at the
American College of Cardiology's annual meeting in Orlando,
Fla., and is submitting a manuscript of his work to a
peer-reviewed heart journal.
"He has really become an integral member of our lab
effort and has continued to inspire and train other
students," Berkowitz says of Gregg.
"It was a great overall experience," says Gregg. "I
think I was really lucky, and I learned a lot."
After graduating in May, Gregg plans to enter a
doctoral research program.
Gregg and Gupta also pursued other areas of interest
while working in the lab. As a side project, Gregg wrote a
software program that integrated his data in a new way to
look at the relationship of calcium release and contraction
length in heart cells. Ion Optix Corp., manufacturer of one
of the instruments used in his study, is adapting the
software for its own use. And Gupta's laboratory techniques
to prepare blood vessels and examine their function helped
cardiology faculty member Kaiko Irani complete his work
characterizing the vascular appearance of a mouse deficient
in a protein called redox-factor 1. For his efforts, Gupta
was second author on a paper published in Circulation
Research last year.
— Karen Blum

A ROLY-POLY SURPRISE

A ROLY-POLY SURPRISE: Katarina
Juhaszova, working with Katalin Szlavecz, unearthed new
findings about isopods.
PHOTO BY HIPS/WILL KIRK
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Katarina Juhaszova is playing an important part
in ascertaining the role that terrestrial isopods —
bugs commonly known as pillbugs, sowbugs and roly-polys
— play in the recycling of nutrients in forest
ecosystems.
Juhaszova's original research, focusing on the effect
that several species of isopods have on soil nutrients, has
been funded with support from a PURA.
Knowing that isopods are not native to the
mid-Atlantic region (they were brought to America during
European colonization), Juhaszova wondered what effect
— if any — the small creatures were having on
the nutritional composition of forest soil, which, over
time, can lead to changes in the forests' plant and animal
composition.
Working under the guidance of sponsor Katalin
Szlavecz, professor in the Morton K. Blaustein Department
of Earth and Planetary Sciences, Juhaszova ventured into
local forests, where she studied the impact that six
species of isopods had on the rate at which leaf litter,
which provides food for the creatures, disappeared. In
laboratory experiments, she also examined how the isopods'
feeding activity alters the soil's organic content and
nitrogen availability.
What she learned surprised her.
"We found that instead of depleting the nutrients in
the soil, which is what has happened with some invasive
species, the isopods actually are having the opposite
effect," Juhaszova says. "Their droppings produce a good
source of carbon for the microbes there, promoting their
growth."
Szlavecz calls her student's results "certainly
interesting and worth investigating further."
"We know that a sudden influx of non-native
detritivores (creatures that eat leaf litter and other
detritus) is likely to change the nutrient availability of
forests over time, and not always for the better," Szlavecz
says. "That's the case with earthworms; though they promote
the decomposition of organic nitrogen, they do it at a rate
that is so high that eventually nitrogen can be lost from
the forests. What we are getting from Katy's research is
that isopods have the opposite effect. Though it would be
far-fetched and pompous for us to draw some big conclusions
regarding the whole ecosystem level process based on Katy's
data, it certainly is worth further scrutiny."
— Lisa De Nike

TESTING TISSUE ENGINEERING TECHNIQUE

TESTING TISSUE ENGINEERING
TECHNIQUE: Athar Malik supports Jennifer Elisseeff's
efforts to repair cartilage and bone.
PHOTO BY HIPS/WILL KIRK
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In a tissue engineering lab where researchers are
making new materials to repair injured knees, noses and
other body parts, senior Athar Malik is performing
critical experiments to determine whether this promising
technique is damaging cells.
Malik, a biomedical engineering major, is conducting a
study to determine if DNA in cells is being harmed by a
chemical reaction that occurs during the tissue engineering
process. His experiments in the laboratory of Jennifer
Elisseeff, an assistant professor of biomedical
engineering, have been supported by a PURA.
Elisseeff has been guiding efforts to repair injured
cartilage and bone without major surgery by injecting a
liquid filled with cells that should promote the growth of
healthy new tissue. When a special light is shone on it,
this liquid hardens into a gel that holds the therapeutic
cells in place. But before this material, called a
photopolymerizable hydrogel, is used in humans, Elisseeff
wants to be sure the chemical reaction used to harden the
liquid is not damaging the helpful cells being injected
into the body. "Our studies so far lead us to believe that
the process is safe," Elisseeff says. "But we want to be as
certain as possible. If we do find cell damage and can
figure out how it occurs, we can try to correct the
problems before moving forward."
To look for signs of DNA damage to the treatment
cells, Elisseeff turned to Malik, who has worked in her lab
since his freshman year. He has contributed to the ongoing
hydrogel research, receiving credit on three peer-reviewed
journal papers, including one in which he was listed as a
lead author. In a letter of support for Malik's PURA,
Elisseeff cited his rapid progress in learning laboratory
techniques, along with his "outstanding work ethic,
dedication and intelligence."
Malik says he had never taken part in formal lab
research before arriving at Johns Hopkins. "One of the main
reasons I joined this lab was to begin applying some of the
things I'd learned in high school and in my classes here,"
he says.
For his current project, Malik fills the chambers of a
multiwell plate with a nutrient solution, then adds some of
the adult goat stem cells that are being used in
Elisseeff's injury repair project. After the cells have had
time to thrive, Malik adds a photoinitiator, the chemical
used to trigger the chemical reaction that hardens a
hydrogel. He next exposes the wells to ultraviolet light
for varying periods, setting off the chemical reaction.
"Our goal is to see if this reaction has damaged the
cells," Malik says.
To find out, he extracts DNA strands from the cells
and uses a lab test to determine their length. Shorter
strands indicate they have been cut — a sign of
damage. "If we see that the DNA has been damaged, we try to
look at it in further detail to find out specifically what
has caused the damage and what can be done to prevent it,"
he says.
After finishing his analysis of the data, Malik hopes
to publish his findings in yet another peer-reviewed
journal article. "I feel very fortunate to have had the
opportunity to work and have an active role in Professor
Elisseeff's lab," Malik says. "When I first joined, she
paired me with older members of the lab so that I could
learn from their experience. Now, I'm helping some of the
younger students."
Outside the lab, Malik serves as president of Tau Beta
Pi, the engineering honor society, and works as a residence
hall adviser. Last year, he received an honorable mention
in USA Today's All-USA Academic Team program. After
graduation in May, he hopes to enter a rigorous M.D.-Ph.D.
graduate program. "I would like to both practice medicine
and conduct biomedical research," he says.
— Phil Sneiderman

The 12th Annual PURA Ceremony
Check out their results —
To recognize the recipients of the 2004
Provost's
Undergraduate Research Awards, an event will be held from 3
to 6 p.m. on Thursday in Homewood's Glass Pavilion.
A poster session in which students will have an
opportunity to display the results of their research begins
at 3 p.m.
At the 4:30 p.m. recognition ceremony hosted by Steven
Knapp, provost and senior vice president for academic
affairs, Theodore Poehler, vice provost for research and
chair of the selection committee, will introduce the
honorees, and Provost Knapp will present the students'
certificates. Also on the agenda is a presentation by
junior Robert Whelan, whose summer research involved the
music of the Shetland Isles. A reception will follow.
The entire Johns Hopkins community is invited.
GO TO MARCH 7,
2005
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GO TO THE GAZETTE
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