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Research at the University of Virginia School of Engineering & Applied Science
IMPACT
f a l l
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V o l U m E 1 1 N U m b E R 1
Engineering aHealthier World
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MPACTI
MPACT is published by the University Virginia School o Engineering andpplied Science. An online version o
he magazine is available at www.seas.virginia.edu/impact.
Writer and Editor
Charlie Feigeno
Contributing Editors
osie Pipkinak Richards
Graphic Design
ravis SearcyMountain High Media
hotography
om Cogill
ddress corrections should be sent to theniversity o Virginia School o Engineeringnd Applied Science, P.O. Box 400259,
harlottesville, VA 22904-4259, or call34-924-1383.
Contents
Reducing Death and
Injury on Our Highways
Innovations in
Biomedical Engineering
Medical Research
Across the School
Exploring Treatments for
Alzheimer’s Disease
n the cover: The Center for Applied iomechanics uses a variety of test dummies
o measure the effects of side and front mpacts on drivers and passengers.
HealtHy InnovatIons
Impact fall 20102
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he aculty members at the School o Engineering and Applied Science conduct researchnot simply because they are driven to gure out how things work, but also because they are
determined to harness that knowledge or the good o humanity. Tere is no more direct way to
help others than to improve their health — and or aculty researchers that means ocusing on
how the human body works.
In laboratories around the School, aculty members are learning how the body responds to
the trauma o injury so they can devise better saety systems or automobiles. Tey are improving
on the body’s own mechanisms or healing, helping surgeons mend bones and reconnect nerves
more eciently. And they are learning
how cells and tissues unction, so they can
develop ways to halt the progress o diseaseslike cancer, diabetes and Alzheimer’s.
Health-related research is the primary
ocus o the Department o Biomedical
Engineering, but there are groundbreaking
programs in virtually every department in the
School. Te Engineering School aculty almost
doubled its research unding rom the Nationa
Institutes o Health in scal year 2010.
We could not have achieved these gains
on our own. What makes these programssuccessul is our close partnership with the
School o Medicine. Te Department o
Biomedical Engineering is a joint program
o our two schools, but a signicant number
o our aculty have joint appointments in
departments like emergency medicine or
orthopaedic surgery.
We understand that the road to
innovation in the 21st century lies on the
border between disciplines.
t
RESEARch At thE U.VA. ENgINEERINg School
Barry W. Johnson
Senior Associate Dean
Associate Dean or Research
U.Va. School o Engineering and Applied Science
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ReDUcInG HIGHWay fatalItIesn 2009 the National Highway rac Saety Administration
reported 33,000 motor vehicle deaths, the lowest since it
egan counting more than three decades ago. Researchers at
he Engineering School’s Center or Applied Biomechanics are
etermined to reduce that gure even urther — and they have the
xpertise, acilities and record o achievement to play a leading role
n this eort.
Since it was ounded 21 years ago, the center has grown
ramatically, thanks to support rom the Engineering School and the
chool o Medicine. It currently has 30 ull-time researchers and 20
raduate students and is poised to expand urther. It just moved to a
ew building at the University Research Park, giving it 25,000 square
eet o laboratory and oce space. Te center is now the largest
University-based impact biomechanics laboratory in the world.
Te highlight o the new acility is a second state-o-the-art
led system, this one designed to analyze the vehicle rollovers that
ccount or one-third o all highway atalities. Te center’s sleds are
ighly instrumented. During a typical crash test, researchers can
ollect 10,000 data points every second rom each o 250 to 300
hannels o inormation. “We lm at more than 1,000 rames a
second and can track the motion o a person during an impact with
submillimeter resolution,” says Je Crandall, the center’s director
and a proessor in the Departments o Mechanical and Aerospace
Engineering, Biomedical Engineering, and Emergency Medicine.
Te center currently has projects under way in virtually every
area needed to reduce trac atalities and injuries. It is helping
to develop more accurate criteria or preventing lower extremity
and thoracic injury, testing advanced vehicle passenger restraint
systems and studying the biomechanics o aging as part o the
Engineering Crash Injury Research and Engineering Network.
It is a partner in the Global Human Body Modeling Consortium
and is also evaluating next-generation crash dummies.
“Many o the injuries that occur during a crash inevitably
are atal,” notes Richard Kent, a proessor in the Departments o
Mechanical and Aerospace Engineering and Emergency Medicine
and the leader o the Automobile Saety Research Group at the
center. “Te only way to treat them is to prevent them. Tat’s what
this center does.”
Center researchers(L to R) JeCrandall, CostinUntaroiu andRichard Kent are
shown with Buster,a biofdelic side-impact test dummy.
READ MORE: www.centerforappliedbiomechanics.org/
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enGIneeRInG HealInG
Botchwey, an associate proessor o biomedical engineering
nd orthopaedic surgery, specializes in the musculoskeletal tissue,
which includes muscles, tendons, bones and nerves. One area in
which he thinks the body could do better is bone. When someone
hatters a bone, surgeons take bone rom a tissue bank and use ito piece together the ragments. “Although this bone allograt has
many o the biological components needed or bone healing, it
s poorly vascularized,” Botchwey notes. “Tis sometimes causes
he allograt to crack and ail, which inevitably means additional
urgery.”
Working with graduate student Cynthia Juang, he coats
he allograt with a synthetic, degradable polymer. Te polymer
eleases a drug that targets S1P receptors in the bone tissue, which
when activated will promote vascularization, enhance integration
with host bone and remodel the allograt.
Botchwey is also developing new techniques to promote
healing o peripheral nerves, bundles o nerve bers that carry
inormation to and rom the spinal cord. When these nerves are
severed, surgeons can repair them by delicately stitching together
the ends. I they have to stretch them, however, the outcomeis usually poor. With Botchwey’s guidance, graduate student
Rebekah Neal has developed a completely novel method o
connecting them without strain. She turned to a process called
electrospinning to produce nanoscale bers that combine a
biodegradable polymer with collagen and laminin, two substances
necessary or nerve growth. Te bers serve as a scaold
connecting the nerve endings, and the laminin encourages the
nerve cells on each side o the severed nerve to grow toward the
target organ.
dward Botchwey is developing new techniques to ampliy and manageatural processes to mend shattered bones and reconnect severed nerves.
As Edward Botchwey sees it, the human body is like a promising undergraduate. It needs a littleassistance to help reach its potential. “Although the body has the means to heal wounds, I’ve neverbeen truly happy with the time it takes or, in many cases, the results,” he says. “My goal is to ndways to more eectively engineer healing.”
MPACTI INNoVAtIoNS IN bIomEdIcAl ENgINEERINg
READ MORE: www.bme.virginia.edu/lct/
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Over the past 18months, Kevin Janes’research has attractedmore than $2.9 million inunding. Te new kinase assay system
that Karin Holmberg (pictured
above) is developing will be put
to use immediately, thanks to her
collaboration with Michael Weber, a
proessor o microbiology and director
o the U.Va. Cancer Center. Weber isdeveloping treatments or melanoma,
a deadly orm o skin cancer in which
kinase signaling is oten deregulated.
He has ound that certain
combinations o drugs have an eect
on melanoma cells that is greater than
the sum o their individual eects, but
he is not sure why.
“Te assay we’re developing can
track the activity o multiple kinasesat the same time,” Holmberg says.
“It will provide the data we need
to understand cell signaling at the
network level, helping us understand
why certain drug combinations are
synergistic. Tis knowledge will help
us choose drug combinations that
will inhibit the growth o melanoma
cells even more eciently.”
a knock-oUtcombInatIon
foR canceR
ne way to describe a human cell is as a very sophisticated circuit board. It
constantly receives inputs rom the world around it and processes them into
hemical or electrical signals that generate cellular outputs. Depending on what is
appening in a cell’s microenvironment, these signals might cause the cell to migrate,
ivide, or dierentiate into another cell type. Tis inormation processing, called signal
ransduction, is the theme o Kevin Janes’ laboratory.
In recent years scientists have made great progress understanding how each
ndividual circuit works. Te next challenge is to understand what happens when clusters
circuits are activated, as is typically the case. “We don’t really understand how pathways
work together on a systems level,” Janes says. “It’s a problem that engineers are ideally
uited to solve.”
One roadblock is that existing methods o analyzing the activities o groups o
athways are slow and cumbersome and permit only a general qualitative assessment.
Working with graduate student Karin Holmberg, Janes is designing a bioassay that is
more ecient at producing quantitative results. He is ocusing on circuits that use kinase
nd phosphatase enzymes, because these chemical signals oten lose their regulation
nd get stuck on or o in cancer and in infammatory diseases like atherosclerosis and
heumatoid arthritis. “By combining our knowledge o enzyme biochemistry with newly
ntroduced instrumentation, we are developing a much more sensitive, high-throughput
method to quantitatively analyze samples or hal a dozen kinases at a time,” he says.
o
READ MORE: www.bme.virginia.edu/janes/
DecoDInG tHe lanGUaGe of
cell sIGnalInG
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ticking yoursel with a lancet is no un, yet that’s exactly what
people with ype 1 diabetes have to do our or more times a
ay. Because their bodies have lost the ability to produce insulin,
hey have to continually monitor their blood sugar and inject the
ormone when blood sugar levels rise too high. While the technology
or doing this has become much more convenient — there are now
lucose monitors that help people interpret these pinpricks and
nsulin pumps that replace syringes — these blood sugar snapshots
rovide only a rough assessment o a person’s insulin needs.
As Stephen Patek, an associate proessor o systems engineering,
otes, “Tere are thousands o small events during the day — rom
ating a doughnut with your 10 o’clock coee to going or a jog —
hat can cause dramatic swings in blood sugar levels.”
Patek is part o a multidisciplinary international team that is
eveloping an automatic continuous system or blood sugar control.
Teir challenge is to develop algorithms that take all these daily
ariables into account. Te ultimate goal o the team, which includes
Proessors Boris Kovatchev and Marc Breton rom the School o
Medicine, is to link glucose monitors with insulin pumps in a closed-
oop system they call the “articial pancreas.” Tis research is unded
y the Juvenile Diabetes Research Foundation, the National Institutes
Health, the National Science Foundation and industry groups.
Patek’s specialties include the optimization o random events, but
he consequences o eating a meal are hardly random. Food ingestion
will always elevate blood sugar levels, just as exercise lowers them.
ypical models used to describe random disturbances don’t work oreople,” he notes. Another issue is the lag-time o up to 45 minutes
ssociated with using the continuous glucose monitor and the insulin
ump. It takes time or the changes in the blood to reach the fuids that
he monitor samples, and it takes even more time or insulin delivered
y the pump under the skin to reach the bloodstream. Patek is building
mathematical models that enable him to bridge that gap.
“Tis is a ascinating project to be involved with,” Patek says.
Te path to having a positive impact on people’s lives is
ommercialization, but it’s a complicated process.”
aUtomatInG DIabetes tReatment
Stephen Patek iscontributing his systemsengineering expertise toa global eort that oneday will make the artifcialpancreas a reality.
s
READ MORE: http://web.sys.virginia.edu/stephen-d-patek.html
MPACTI mEdIcAl RESEARch AcRoSS thE School
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When you take a really close look at
muscle — and graduate student Bahar
Shara (pictured above) has — you
start noticing a variety o dierent
tissue geometries. Shara’s challenge
has been to create three-dimensional
computational models that link a
muscle’s microscopic morphology and
properties to muscle unction.
For instance, using modeling,she has ound that the shape o its
ascicles, or bundles o muscle bers
or cells, gives a muscle its ability to
adapt to the sheer orces that act on
it. Dierent ascicle shapes are more
appropriate or dierent sheer orces
and are ound in dierent muscles.
She is also studying the mechanics o
the myotendinous junction, the point
o insertion o muscle bers into thetendon, to explore the mechanisms
that contribute to a high rate o injury
in this region.
Shara came to her research
without any knowledge o
biomechanics and muscle anatomy.
“I’ve ound it ascinating to apply the
principles o mechanical engineering
to the human body,” she says.
tHe sHape of
yoUR mUscles
hether you can sprint 100 meters in 9.8 seconds like the Olympic gold medalistUsain Bolt or are content to run a ew laps around the track ater work, you are
kely to experience a hamstring strain sooner or later. Silvia Salinas Blemker, an assistant
roessor in the Departments o Mechanical and Aerospace Engineering and Biomedical
Engineering, is taking a resh look at why certain muscles like hamstrings are particularly
rone to injury.
Te hamstrings run along the back o the thigh and attach on both sides o the
nee joint. Tey are responsible or pulling the oot rom the ground with each stride.
raditionally, researchers treat them like anatomical rubber bands, uniormly elastic along
heir length. Blemker is taking a closer look, relating muscle structure to its mechanical
roperties and ultimately to its unction.
W
tHe GeometRy of
mUscle stRaIn
Recreational athletes and Olympians alike may suer ewer muscle strains inhe uture, thanks to research on muscle geometry by Silvia Blemker.
Blemker’s work combines computation with magnetic resonance imaging and anatomical
measurements. Te goal is to create a computational model o the musculoskeletal systemhat incorporates its complex three-dimensional architecture and geometry.
In the process, she has discovered a signicant marker or injury susceptibility that could
e applied to all muscles. endons are embedded in muscle to provide a rmer attachment.
Tese internal tendons, which vary in width, length and thickness, are called aponeuroses.
Blemker ound that strains occur in muscle tissues adjacent to narrow aponeuroses.
o determine i aponeuroses width is an important actor in injury, Blemker proposes
o take magnetic resonance images o members o a sports team at the beginning o their
eason and then track them to see i people with narrow aponeuroses do indeed become
njured more oten.
READ MORE: www.mae.virginia.edu/muscle/
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Non-Prot OrganizationUS PostagePAID
Charlottesville, VA Permit No. 164
University o Virginia Ofce o the DeanSchool o Engineering and Applied ScienceP.O. Box 400246Charlottesville, VA 22904-4246
www.seas.virginia.edu/impact
nchan Kwon, an assistant proessor o chemical engineering,
takes the old DuPont advertising slogan “Better Living through
Chemistry” quite literally. He is combining his expertise as a
chemical engineer and his knowledge o proteins, honed in industry
and university research labs, to cure neurodegenerative diseases.He is particularly interested in Alzheimer’s disease. One
theory or the cause o the disease places the blame on a peptide
called amyloid-beta. Peptides, like proteins, consist o a chain o
amino acids. Individually, amyloid-beta peptides are harmless,
but when they clump together they disrupt communication
between neurons and cause them to die. “Finding a substance
that could modulate amyloid-beta aggregation is a promising
strategy or preventing or treating Alzheimer’s,” Kwon says.
Kwon is screening small molecules already approved by the
FDA and other peptides to search or compounds that couldmodulate amyloid-beta aggregation saely and eectively. He
has identied a number o promising molecules and is applying
to the National Institutes o Health or unding to ne-tune the
characteristics o these molecules and to conduct animal studies.
His research on peptides has been similarly productive. “We still
need to do more testing,” he says, “but we are hopeul that we
will be able to make a dierence.”
READ MORE: www.faculty.virginia.edu/kwon/
DIsRUptInG tHe bIocHemIstRy of
alzHeImeR’s DIsease
I
IMPACT
nchan Kwon is searching or aubstance that could prevent theormation o amyloid plaques, aharacteristic o Alzheimer’s disease.