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Cover Story

Inner-Space Invaders

‘ Two UK researchers are creating nanoparticles

» loaded with cancer-killing drugs. The tiny spheres
are further engineered to target and infiltrate
specific diseased cells. 2

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Features

Shaping the Future of Software
On the wings of 17 years in industry, Jane Hayes

is designing software to further UK research and
empowering students to tackle real-world problems. 8

Mounting an Attack on a Furtive Form of Plaque

Rob Lodder unites fiber optics and mathematics
in a probe that lets doctors do preemptive, on-site
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44

 

   

 rmed with therapeutic drugs. nanoparticles injected into the body move

along in the bloodstream toward their target—a cancer cell, The mighty
macrophages spot a few of them and gobble them up. But these nearly invisible
legions of stealthy. infinitesimal specks make it past almost all the sentries. invade
the target cell. and release their potent drugs.

This scenario is being perfected by Russ Mumper and Mike lay in the University
of Kentucky College of Pharmacy. Mumper‘s recent work with nanoparticles,
funded by the NIH National institute of Allergy and Infectious Disease, holds great
promise for treating various cancers and fighting viruses like lllV.

“Mike and l are involved in several projects to deliver drugs in new and better

ways.“ says Mumper, an assistant professor of pharmaceutical science who re—
turned to UK four years ago after spending seven years in industry “Using

 

 nanotechnology, we’re able to pack-
age drugsintinyspheresandsendthem
to specific cells.“

Nanoparticles continue to gain at—
tention and earn respect. They're so
small they are measured in nano—
meters—billionths of a meter. To put
this in perspective, the width of this
letter “I“ is about a million nanometers

“The essence of nanotechnology is
the ability to work at the ultra-small
level." says Jay, a professor of pharma—
ceutical science and director of UK’s
CenterforPharmaceuticalScience and

     

 

Technology [see sidebar, p. 4]. “Simply
put. the engineering idea is to design
things from the inside out at the nano
scale to create exactly what we want.
Nanotechnology offers limitless possi—
bilities in the fields of pharmacology
and medicine. It provides new ways for
us to deliver specifically targeted, po—
tentially life—saving drugs.”

Tinkering with the Very Tiny

In the battle against cancer and other
devastating diseases, pharmaceutical

Russell Mumper (left) and Mike Jay have col
laborated on various research projects since
the early ’905, when Mumper was a graduate
student and Jay his adviser. I

 

companies are developing new drugs
every day. Many of these drugs work
fine in cell culture tests but then fail the
crucial water test.

Around 40 percent of all newly dis—
covered compounds have poor water
solubility or none at all. This is a prob—
lem because the human body is a huge
reservoir of water—we're two—thirds
water. “Lots of drugs get killed along
the developmental pipeline because
they can’t be formulated to be used in
the body," Jay says.

wm/nucd on p 5

 

 UK's Center for Pharmaceutical Science
and Technology

On its hopeful way to FDA approval, a
drug is poked and prodded, weighed
and measured. Every move it makes is
analyzed and then reanalyzed. The pro-
cess is tricky, time-consuming and
daunting. But at UK’S Center for Phar-
maceutical Science and Technology
(CPST), this process is streamlined in
the manner of one-stop shopping.

“We’re a full-service facility,” says
Mike Jay, director of the center and a
professor in UK’s College of Pharmacy.
“We can work with someone from the
idea stage all the way through Phase l
and early Phase [1 manufacturing of the
drug for clinical trials, and we can do
all of this right here in the College of
Pharmacy building.” Phase 1 testing in—
volves giving a drug to a small number
of people to see what dose is safe; Phase
ll testing entails giving a larger number
of participants the appropriate dose
over a longer period of time to see if the
drug is working and whether it has any
long-term side effects.

The CPST, which opened its doors in
1986, has formulated drugs into inject—
able liquids, freeze-dried products, tab-
lets and capsules, dermatological
products, and produced up to 5,000
units at a time. UK is one of two univer-
sity-based, FDA-registered pharmaceu-
tical manufacturing centers with the
unique ability to freeze-dry products.
To date, the CPST, which utilizes strict,
current Good Manufacturing Practices,
has completed over 200 contract
projects.

“We target four classes of clients:
university researchers, biotech compa-
nies, pharmaceutical companies that
gross $25 million to $250 million a year,
and the NIH," says Frank Manella, man-
aging director of the center. He adds
that the center has increased client bill-
ings from $200,000 in 1996 to $1.5 mil-
lion last year. “We've been on a pretty
solid growth curve, thanks to the lead-
ership of Dr. Jay and the College of

Pharmacy’s solid support. We plan to
take it even higher—to $10 million plus
by 2007.”

Manella, who was hired in Novem-
ber of last year, is a “wonderful, new
addition" to the center, Jay says.

Manella started out 30 years ago as a
bench research chemist, working on
new semi-synthetic penicillins. He even-
tually ended up heading Pfizer's world-
wide sterile penicillin packaging and
freeze—drying operation in Terre Haute,
Indiana.

“1 got involved in new business de—
velopment along the way and traveled
extensively in the US, Japan and Eu-
rope looking for new pharmaceutical
compounds to license, develop, and
finally—afterFDA approval-—marketto
physicians and pharmacists," Manella
says. “This is much the same thing the
CPST does for its current clients." He
says he wanted to come to UK because
of the ambience of a university set-
ting—the camaraderie, curiosity and
stimulation he saw here when he
worked last year with the College of
Pharmacy as a consultant.

The CPST will be growing soon, and
moving. “We'll be moving to UK’s
Coldstream Research Campus [nearthe
crossroads of 1-75 and 1—64, six miles
from the Lexington campus] next year
and plan to open our doors early in
2005,” Manella says. “We’re hoping that
our presence there will also entice the
building of commercial manufacturing
facilities alongside us. That way entre-
preneurs could easilysegue from Phase
II to Phase III clinical manufacturing
and then scale up forcommercial quan-
tities."

“We’ll retain the current facility here
in the College of Pharmacy building,
too." Jay says. “What will happen is the
manufacturing of sterile products will
be done at Coldstream, and the manu-
facturing of non-sterile products will
continue here on campus.”

Manella mentions an-
other tangible benefit of
the CPST expansion.
“Historically, way too
many of the top College
of Pharmacy graduates
leave Kentucky. I'd love
to see some of this brain
drain stop."

The center will pro-
vide the opportunity for
UK graduates and oth-
ers to put their skills to
work right here at home.
“We hope to add more
than 40 people to the
center in the next 12 to
18 months," he says,
“and if things go accord-
ing to plan we could be
upto around 100 people
at Coldstream doing a
three-shift operation by
2007."

Frank Manella is managing
director of UK’s Center for

Pharmaceutical Science

and Technology (CPST), one of two
university—based, FDA-registered
pharmaceutical manufacturing centers
with the unique ability to freezedry

products.

continued from p. 3

Sohere‘sthe researchchallenge:How
doyou increase the water solubility ofa
drug that doesn‘t want to dissolye in
water"?

“lnorderforadrugtobeinjectableor
to be absorbed from the stomach. it has
to show some water solubility." says
Jay. “One way to do this is to fake it—
put the drug into an environment in
which it is soluble. an oil droplet, for
instance, and send it into the body this
way." This idea is at the heart of the

researchers new patented process.
which they term “nanotemplate engi—
neering."

"The drugs that we would like to for-
mulate are not very water soluble. but
they are soluble in oil." Mumper says.
These miniscule spheres—under an
electron microscope they look like a
cluster of marbles—can be engineered
to seek out a particular tissue or cell in
the body. After the drug reaches its
target. a cancer cell. let‘s say. the drug

is welcomed in and is released from
the particles. It then leaches out into
the cell. killing it.

But eyerybody knows water and oil
don‘t mix. So how do these designer
particles manage to pass through wa—
ter to find their designated target? The
answer. Jay says. has to do not only
withsizebutalsowithchernicalscalled
surfactants.

“To make oil and water mix. we
resorttoa bitofscientific trickery."Jay

5

 

  
  

  
  
  
  
 
 
 
 
  
   
   
 
 
  
  
  
  
  
  
 
 
  
  
  
 
 
  
   
 
 
  
  
  
  
  
  
 
 
 
  
  
 
 
   
   
  
  
 
  
  
 
 
  
  

says with a hint of a smile. “A surfactant
is a surface—active agent—hand soap is
a good example. In our case, it’s some—
thing that will align at the interface
between oil and water.”

The surfactant they add to their mix,
he explains, has an oil—friendly part that
extends into the droplet and a water-
friendly part that lies on the surface of
the droplet,virtuallysurroundingit.The
surfactant serves as a kind of mediator.
It’s what permits, in large part, the un-
likely marriage of water and oil. The
purpose of the surfactant is to stabilize
the oil droplet, to keep it well sus—
pended.

“These microemulsions are stable,"
Mumpersays. “They won‘tseparate over
time, like oil and vinegar will, for ex-
ample, and this stability is exactly what
we want." He adds that he and Jay have
carefully chosen an oil that is a liquid at
slightly elevated temperatures (1200 F
or so), but at room temperature is a
solid. “When we cool the mixture back
to room temperature, the droplets trans—
form into tiny, solid particles. [Sub—
stances that can change form are fairly
common—thinkofwaterand ice.] They
have the drug inside them, and they’re
still coated with the surfactant."

The researchers nanoparticletinker—
ing doesn’t stop here. “By using ‘recog-
nition molecules‘ attached to the
surface of the particles, we can direct
them to specific parts of the body, say.
a receptor on a tumor.” Jay explains.
Nanoparticles can be easily injected or
can be dried and incorporated into a
tablet, he explains. “The particles head
for the cancer cell and bind to a recep-
tor. What we hope will happen then is
that the cancer celE will engulf the par—
ticle and. in doing so. engulf the drug
that wiIE teach out into the cell.”

       

A Magic Bullet

“People might wonder, ‘Why nanotech-
nology? Why nanoparticles?” Mumper
says. “Well, there’s one primary reason.
To be effective, more and more drug
therapeutics have to be delivered to
specific cells, tumor cells in the brain
or in the liver, for example. And of
course these cells have to be able to
recognize and take up the material."

Nanoparticles are so small, Mumper
says, that cells can easily take them
in——the typical cell is around 8,000 na—
nometers. “It‘s kind of like a magic bul-
let. lt‘sa way to targetspecific nefarious
cells without damaging healthy cells in
the same neighborhood.“

And Mumper gives another reason
why these miniscule warriors are so
effective—they can circulate in the
body for a relatively long time without
being removed by macrophages and
other cellular police.

“Basically, the bigger the particle—
the more noticeable a foreign body
is—the more attention it attracts," he
says. “So nanoparticles can move
around undetected for a long time."

Another important thing about their
process, says Jay, is that it‘s inexpen—
sive. Instead of using pricey fluidizers,
homogenizers and other equipment
that can be used to make new pharma-
ceutical products, the researchers sim—
ply let nature take its course.

“We literally throw the materials in—
a mix of oil, water, surfactant, and the
drug—and gently mix them together,"
Jay says. adding that the materials they
use to make nanoparticles are all FDA—
approved for use in humans. He and
Mumper have patented this method of
making nanoparticles, one of six pat—
entstheyhofdjointlyinthe field ofdrug
delivery.

A Special Collaboration

“As a junior chemistry major at UK in
'86, I needed to do independent re-
search as part of my coursework,"
Mumper recalls. “I could have done it
in the chemistry department, like most
chem majors do, but a friend of mine in
the College of Pharmacy convinced me
to go work there. I did. and Mike be—
came my mentor." Mumper adds, with
a smile, that Jay was good enough to
allow him to make mistakes “all on my
own, which accelerated my learning
curve."

Jay was Mumper‘s graduate student
advisor from 1988 to I991. and around
that time they co-authored six papers.
“Russ was a very capable student and a
solid researcher from the beginning,"
Jay says. “One of the first things you
learn as a faculty member working with
graduate students is that the goal is to
make them better than you. I've defi—
nitely met that goal with Russ."

Over the years they stayed in touch,
keeping each other up to date on their
research, while Mumper was working
in industry with Burroughs Wellcome
and, later, GeneMedicine in Texas. Then
in I999 Mumper returned to UK as one
of the first new faculty members hired
through the Research Challenge Trust
Fund (RCTF) initiative. commonly
known as Bucks for Brains.

“In ’99thecompanylwas working for
wassoldso this wasagood timetolook
around,” Mumper explains. With “sub—
stantial help" from Bob Blouin. former
associate dean of research and gradu—
atestudiesin pharmaceuticalsciences,
Mumper was offered the job of assistant
director of the Center for Pharmaceuti-
cal Sciences and also a tenure-track
position in the College of Pharmacy as
RCTF faculty.

 University of Kentucky Research

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“This was an ideal position for me,”
Mumper says. “I knew I’d be able to do
research on drug-delivery systems and
teach, but also, as assistant director of
the center, do a lot of product develop—
ment, which is exactly what I’d been
doing in industry.”

When Mumper came back to UK,
Jay’s lab was working on water and
fluorocarbon microemulsions for drug
delivery to the lung, and Mumper had
recently been working, in industry, on
ways to make small particles.

“So Mike and I started talking about
this, and 1 said, ‘Have you ever tried
making a particle in those
microemulsions?’ Mike said no. ‘What
if we took your fluorocarbon micro-
emulsion and tried to make particles
within the individual droplets?’ We did
some experiments and it worked."
Mumper says this integration of their
research backgrounds and experience
is typical of how they collaborate.

the Business of Research

AmongtheirdiscussionsafterMumper’s
return to UK was the idea that they
should think about formingacompany
together sometime down the line, an
enterprise that would get them into the
drug—delivery business.

“We started submitting invention dis—
closures related to our work with
microemulsions and nanoparticles, and
thought we might form a company in
four or five years to license these intel-
lectual properties,” Mumper says. “But
then after about a year and a half we
decided, why wait.”

“Our work was coming along well,
and we’d been watching new develop-
ments, reading the literature closely. So
we decided that if we waited, we could

getscooped,” Jay says. The result of this
forging ahead was the birth in 2000 of
NanoMed Pharmaceuticals Inc. Co~
founders .lay and Mumper were joined
in 2001 by Stephen Benoit as the
company's CEO.

“Russ and l went to a venture fair in
Kalamazoo, Michigan, and made our
presentation about the nanoparticle
work we were doing,” Jay explains. “Af~
terwards, Stephen came up to us and
said he liked what he‘d heard. He told
us about his background, which is very
impressive, and then he said, ‘How
would you guys like a CEO?’ It was a
very serendipitous meeting." Benoit,
who holds an MBA in finance, brings to
this venture over 20 years” experience
in biotechnology, disease-manage-
ment, pharmaceuticals, and finance
services industries.

Jay explains that NanoMed is focus-
ing on translating their research into
the marketplace, and despite the eco-
nomic downturn in the United States in
the last couple of years, market oppor-

 

The nanoparticles that lay and Mumper
designiunder an electron microscope
they look like a cluster of marbles—are
engineered to contain a cancerakilling
drug and to seek out a particular cell in
the body. After the particle reaches its
target and is welcomed in, the drug is
released into the cell, killing it.

        
   
  
    
 
  
   
 
   
  
   
  
   
  
  
   
 
  
  
  
  
  
  
  
  
   
      
     

tunity is good, he says. “The global
market for advanced drug—delivery sys-
tems was more than $16 billion in 2000
and is estimated to grow to more than
$27 billion in the next five years.”

“Resources are NanoMed's biggest
challenge, no doubt," says Mumper.
“Our labs continue to do well, and we'd
like to commercialize this technology
for biomedical applications, but you
need money to perform the safety-tox-
icity studies in animals and do early
clinical trials."

The general rule for product develop—
ment, Jay adds, is that each product
costs about a million dollars to get into
clinical trials. “Then the weeding pro-
cess starts," he says. “Of every 250 drugs
that enter clinical trials, only one will
get approved by the FDA. So drug com-
panies and investorssink a lot of money
into the process in hopes of the big
score. People should understand that
this is why drugs are so expensive. It’s
not because the companies are over-
paying the scientists," he laughs.

But Mumper is undaunted by these
challenging stats.

“A primary reason i came to UK,"
Mumpersays, “is because i was ready to
make a long-term investment in this
research and translate it to market. its
also an investment in our state. Ken-
tucky-based businesses like NanoMed
can help keep some of our top gradu—
ates from leaving Kentucky."

“My greatest hope,” says Jay, “is that
some of our technology will make it to
commercial products. in 15 years I’d
like to be able to look back and say,
‘Notonlywasitagreatride,butwhat we
discovered and developed is being used
to help people in measurable ways.”

 Shaping
the
Future of

” ‘mworriedaboutyt>urdaughter."thekindergar
tenteachertoldJane'smotheroyerthe phone.
“She‘s drawing hieroglyphics eyerywhere."

The parent-teacher conference the next day re-
yealedtliest>iii'ceoltliemysterittussymhols—Dad.

A captiyated liye year old. Jane would sit at the
dining room table each night with her father’s
computer printouts. copying the Greek symbols——
deltas and sigmas. “To this day my handwriting isall
crazy—l don‘t form any of my letters correctly——
because I taught myself to write from his printouts.

"My mom loyes to tell this story" Jane Hayes
adds. laughing.

This encounter may haye ruined her penman—
ship. hut she didn‘t abandon computers. ln tact.
l‘layes went on to spend 17 years in industry, rising
through the ranks from systems analyst to ct irpt rrate

 

 'D

vice president, and now shares her ex-
perience with University of Kentucky
students in a software engineering pro-
gram she's creating. Her goal: design
software to further UK research and
empower students to tackle real-world
problems. As an assistant professor of
computerscience. Hayes is addressing
these problems through ongoing re-
searchon software maintainability and
reliability. And programs used by NASA
and other industrial partners. as well as
software written by her own students,
are the subjects of her experiments.

Girl Power

ln response to the perennial gender
question about women in her field.
Hayes shares an experience from a re—
cent international conference on soft-
ware engineering: “Of three keynote
addresses. one was given by a very
impressive woman, and it was titled
something like ‘Women in Computer
Science: Must There Be So Few?”

In the hour—and—ahalf talk about her
NSF-funded research, the speaker

Jane Hayes spent 17 years in industry,
rising through the rants from

systems analyst to corporate vice
president, and now shares her
experience with University of
Kentucky students in a software
engineering program

she’s creating.

 

recounted her focus-group findings
and gave international stats, such as
how more women than men work in
computer science in Singapore. “Then
she showed the US. stats in industry
and academia, and, of course, it's very
depressing," Hayes says.

“But as someone who has been the
only female in most of my organiza—
tions, I'd say this to the conference orga-
nizers: it would have been more effective
ifyou had a male give the speech on ‘why
so few women?’ and if you had a female
give a technical keynote.

“l think it leaves the wrong impres—
sion with the young males in the audi-
ence," Hayes says and pauses, “who
are really the ones that you need to
worry about. Most of the professors
around here get it: they value equality
and diversity. But what the young up-
and—comers will remember from this
conference is, ‘Oh yeah, there was only
onegirlwho gaveakeynote,andallshe
did was show a bunch of stats about
whythere aren'tmoregirlsin computer
science?"

One of the things the speaker didn’t
address, but Hayes firmly believes, is
that successful females have to be su-
per self-assured. “You have to say, ‘I‘m
not the token female. Bring it on.‘ You
have to be just cocky enough to believe
you're getting this job because you’re
awesome, not because of your gen-
der.“

Hayes says she owes some of this
empowered attitude to her mother, who
is also in the computing field, and her
father. “I’d be curious to see how many
female engineers were daughters whose
daddiesdidn'thave anyboys,"shesays,
“because that’s the case in my family.
My dad had two girls. And that may
have something to do with my career
choice—if Dad believes I can do it, 1

Long before the adventof “Bring Your
Daughterto Work Day," she’d tag along
with her parents to work. “While I was
there I taught myself to program in
BASIC and FORTRAN on ancient com-
puters most people have never heard
of," says Hayes, an Ohio native whose
family moved around a lot based on
her dad‘s positions, including Wright-
Patterson Air Force Base, General Mo-
tors (“He was one of the inventors of
the V-6 engine," Jane says with obvious
pride), Imperial College in London,
England, the Air Force Academy, and
the University of Southern Mississippi,
where he was vice president for aca-
demic affairs.

Hayes attended Hanover College. The
liberal arts school on the Indiana-Ken-
tucky border didn’t have much in the
way of computers, she says. Hayesstarted
out in what she calls a “fluffy" major—
politicalscience—butdecided in herjun-
ioryearto add geologyasadouble major.
The geology department had something

 

        

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 special to offer—one computer.

When she got out of college, Hayes
took computer science classes in the
summer. Then, based on her geology
degree and experience with maps, as
wellaslimited computer programming
experience, she got hired by the De—
fense lntelligence Agency. “They
wanted government employees to be
able to do all of the computer program—
ming. They told me to learn this guy’s
job so they didn‘t have to contract it
out,“ she says. The task involved crack—
ing the code of a programmer/baseball
fanatic.

“He thought he’d be really cute and
name all his variables after baseball
players. So I had to try to figure out how
this program worked with Joe DiMaggio
and Pete Rose—totally meaningless
variable names. It was a digital imaging
system. so it was very complicated."
This experience instilled a career—in—
spiring passion in Hayes—software
maintainability—“writingsoftwarethat
other people can easily modify." After
deciphering the inner workings of this
Top Secret system, used to maintain a
database of aerial photographs, Hayes
was hired as a senior systems analyst at
Science ApplicationsInternationalCor—
poration (SAIC) in 1984.

“SAIC is the largest employee—owned
technology company in the United
States.“ Hayes says. “It was formed by a
small group of very entrepreneurial
nuclear physicists, who were commit—
ted to sharing the wealth. They set up
an internal stock market—you can only
have stock ifyou’re an employee—and
it’s generated many, many millionaires.”

Hayes's projects at SAIC, including
the Navy's Tomahawk cruise missile
system and nuclear power plant con—
trol systems, involved writing software
with life or death ramifications and the

concept of verification and validation.

“Validation is making sure that you
built the right software. Verification is
making sure that you built the software
right," Hayes says. “Anytime you need
to trust a software system with anything
that could involve potential loss of hu—
man life, damage to the environment,
or loss of huge sums of money, you
should be willing to spend the extra
money on software verification and
validation to make sure thatyou’ve done
everything possible to minimize that
potential risk."

Hayes spent 16 years at SAIC. and by
1999 as corporate vice president she
was managing more than 230 employ—
ees,one$50million contract, anda$35
million—a—year business unit.

“At SAlC l felt that they treated me
like an engineer or like a manager, that
my gender didn’t matter,“ Hayes says,
laughing “I certainly didn’t see them
holding me back.“ When she started at
SAIC, she was one of two female engi-
neers; when she left SAIC, the company
was about 25 percent female.

“l bet 1 got calls every month asking
me to start my own company. Groups of
people within SAIC would say, ‘Start
your own woman-owned business.
We’ll all come and work for you.” But 1
didn’t want my own business. i knew
how hard it was being a manager at
somebody else’s company, and I was
already working too much."

Hayes continued to work at SAIC and
in 1990 started her PhD. while she was
pregnant with her daughter, Chelsea.
“Every time I would get a promotion,
SAIC would give me 10 new people to
oversee. My advisor at George Mason
University, Jeff Offutt, would ask, ‘How
many more people? Ten more obstacles
to finishing that Ph.D.' He'd tease,
“You’re never going to make it.”

But Hayes was determined. She fin-
ished her Ph.D. in 1999, five years after
having her second child, David. She says
getting her degree is a testament to her
husband Greg‘s strong support and was
inspired by her mother's return to—and
completion of—college at age 47.

Flct II: Flcademia

“l was to the point where I had to com—
mit to executive management for the
rest of my career," Hayes says, “but I‘d
been itching to go into the academic
world for quite a while. I figured this
was really my last chance to go and do
something different.”

That itch lead to an interview at UK.
Miroslaw Truszczynski, computer sci-
ence chairman, says, “She definitely
had strong academic credentials, our
primary consideration, but what truly
set Jane Hayes apart from other people
in the pool was her significant indus—
trial experience. That is very important
because we need people who can re—
late their own experiences to our stu-
dents and who can convincingly speak
about what careers await them.

“She had a very clear vision, which I
thought was quite different from the
rest of the people we interviewed. She
knew what she wanted to do." Hayes
would be tackling more than the usual
responsibilities of developing a research
program and teaching students: her
teaching role would involve building a
curriculum from scratch because there
were no software engineering courses
at UK. “She was looking for that type of
opportunity,“ Truszczynski says.

Hereagernesswasimportantbecause
the department knew the absence of
software engineering was a weakness
of the UK program, he says. “Over the
years, in conversations with people in

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computer and software companies in the Lexington area, they had complained
about a lack of understanding—not only in our graduates, but in graduates from
other programs as well—of the process through which software is designed,
assessed and redesigned.”

Since her arrival at UK (under the Research Challenge Trust Fund initiative) in
January of 2001, Hayes has developed three graduate-level courses. “Her classes
have very high enrollment There would probably be 40 to 50 students in each class
if we let them—we try to limit it to 30 to 35 students—but there‘s certainly more
interest than seats in the class,” says Truszczynski. The computer science depart»
ment has 2