impact fall10

7/29/2019 Impact Fall10

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Research at the University of Virginia School of Engineering & Applied Science

IMPACT

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V o l U m E 1 1 N U m b E R 1

Engineering aHealthier World

eveloping eadersD L nnovationIof



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


http://slidepdf.com/reader/full/impact-fall10 3/8Impact fall 20103

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/




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/



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




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



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/




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.

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