FALL 2008

ExpLoring rEsEArch At thE

University of nebraska Medical center

And bEyond...

discoverUNMC

targeted delivery to ailing

bones

UNMC Discover is published twice a year by the Vice Chancellor for Research and the Department of Public Affairs at the University of Nebraska Medical Center. The magazine is supported by UNeMed Corporation, the technology transfer organization for UNMC.

Issues of the magazine can be found at www.unmc.edu, News link. Permission is granted to reprint any written materials herein, provided proper credit is given. Direct all requests to ekumru@unmc.edu. Subscriptions to UNMC Discover are free. To subscribe, go to unmc.edu/discover.

UNMC’s mission is to improve the health of Nebraska through premier educational programs, innovative research, the highest quality patient care and outreach to underserved populations.

UNMC is accredited by The Higher Learning Commission of the North Central Association of Colleges and Schools (HLC-NCA) and enjoys full accreditation of all its professional academic programs.

UNMC does not discriminate in its academic, employment or admissions programs, and abides by all federal regulations pertaining to same.

Director of Public Affairs: renee Fry, J.d.

Senior Associate Director: tom o’connor

Managing Editor: Karen burbach

Publications Editor: Elizabeth Kumru

Design: daake design

Photography:scott dobry

Elizabeth KumruAndrew nelson

dewayne gimeson, chadron state college

Research Advisory Board:

ExpLoring rEsEArch At thE

University of nebraska Medical center

And bEyond...

the research enterprise at the University of nebraska Medical center continues to grow, against the odds. When the economy struggles, institutions often view their research dollars as discretionary budget items that can be reduced, rather than seeing basic discovery as the engine that ultimately revives the economy. the national institutes of health (nih) is an example of this phenomenon.

the nih is the most successful and most respected biomedical research institution in the world. its support of the basic sciences is unique. For 50 years or more, the nih has provided the basis for most of the major discoveries in human biology. these discoveries have led to improved therapies, which have prolonged and enriched lives. nevertheless, over the past few years, the annual funding increases for the nih have failed to meet inflation and the availability of nih dollars has fallen by about 25 percent.

We are losing a myriad of opportunities to support wonderful, innovative projects. We do not know which discoveries will most directly lead to improved diagnosis, treatment or cure; but we do know no gains are made without discovery. We hope and trust that our leaders in government and in the private sector will see the grave error inherent in this strategy and change directions, soon.

nevertheless, the competitive environment is intense and for many institutions, disheartening. but at UnMc, we have had continuous gains. the first quarter for this fiscal year set a new record for total extramural research funding of more than $32 million.

this remarkable achievement is the result, in part, of the determined efforts of a reliable corps of deans, directors and department chairs who understand well that the principal role of the academic health sciences center is discovery. these men and women have worked hard and used great vision to keep or recruit outstanding scientists and nurture them. of course, the fundamental strength of our research enterprise is in the scientists themselves, whose creativity and performance under duress has been remarkable.

this issue of UnMc discover focuses on a few of these admirable men and women. it is impossible to read about their excellent, innovative work and not see with greater clarity why UnMc is succeeding against the odds, and why it is so important to expand the research enterprise globally.

tom rosenquist, ph.d. UnMc Vice chancellor for research

discoverUNMC

success against the odds

Thomas Rosenquist, Ph.D. • Kenneth Cowan, M.D., Ph.D.

Courtney Fletcher, Pharm.D. • John Gollan, M.D.

Robert Lewis, Ph.D. • James Linder, M.D.

Keith Mueller, Ph.D. • Rubens Pamies, M.D.

Jeffrey Payne, D.D.S. • John Reinhardt, D.D.S.

Warren Sanger, Ph.D. • James Shull, Ph.D.

Joe Sisson, M.D. • Shelley Smith, Ph.D.

Virginia Tilden, D.N.Sc. • Paula Turpen, Ph.D.

Margaret Wheelock, Ph.D. • Irving Zucker, Ph.D.

Nature inspires UNMC scientist

FALL 2008

lotus leaf and fake diamonds lead to better orthopaedic implantsnew coating makes implants more durable 4

apathy – why should you care?drug jolts people to care about their

chronic illness 7

growing our ownUnMc researchers mentor

junior investigators 10

targeted deliverynew system taxis drugs to ailing bones 14

the care connectionnursing study examines new model

of care for chronic disease 20

determined to make earlier diagnosis a realitypancreatic cancer eludes detection –

but not for long 22

under the microscopeclinical researcher co-authors largest

study on hiV drugs 26

contents

i INNOVATION

i

Inspiration often comes from unexpected places.

Just ask UNMC’s Fereydoon Namavar, Sc.D.

In the case of a coating he designed for orthopaedic implants,

the scientist – who worked on NASA’s Mars Rover, Star Wars

and optical communications projects before entering the world

of biomedical research 10 years ago – found inspiration in his

mother-in-law’s jewelry case and the leaves of the lotus flower.

One day a few years back, Dr. Namavar listened as his

mother-in-law shared how much she liked her cubic zirconia

jewelry – except for one thing that bothered her.

“When it would get wet, it would fog up,” said Dr. Namavar,

professor and director of the nano-biotechnology laboratory in the

UNMC Department of Orthopaedic Surgery.

While bad news for his mother-in-law, this was an epiphany

for Dr. Namavar.

A common issue with implants is wear and tear because

joint surfaces rub together. This can lead to repeat surgeries, as

well as send an unhealthy mix of wear particles into a person’s

blood stream.

The wear and tear happens, in part, because surfaces used on

orthopaedic implants are too soft and lack the ability to stay wet.

With orthopaedic implants, ideally, it is important that one

of the two contact surfaces be wettable, while the other is

hydrophobic or rejects water, Dr. Namavar said. He needed

opposites, a Yin and a Yang.

“If both were wet, the surfaces would stick together and

drastically increase friction,” Dr. Namavar said. “But, when

Lotus leaf and fake diamonds lead to better orthopaedic implants by CHUCK BROWN

� fall 2008

you have these opposites together, you have lower friction and

smoother motion on the surface.”

Dr. Namavar’s ears immediately perked up when his mother-

in-law complained about how cubic zirconia fogs up when wet.

“I knew I had my substance,” he said. “I thought, ‘here is a

material that could be hard and also seems to be able to stay wet.’”

In other words, cubic zirconia might work just as well in a hip

joint as it does in a gold tennis bracelet.

As he designed his implant coating, Dr. Namavar wanted to

alter the properties of cubic zirconia to attain maximum wettability.

The cubic zirconia would provide the Yin (wet) to his existing

model, the lotus leaf, the Yang (dry).

The lotus leaf is considered a symbol of purity in many cultures

because of its self-cleaning properties.

“When a drop of water hits a lotus leaf, it rolls off the surface,

washing away dirt and dust,” Dr. Namavar said. “This is because

the lotus leaf is water resistant, or hydrophobic.”

Hydrophilic (wettable) and hydrophobic properties of

substances are actually flip sides of the same coin and thus

identical at a nanostructure level, he said.

As a result, Dr. Namavar decided to alter the physical

properties to mimic the hydrophobic lotus leaf to make his coating

super-hydrophilic or more wettable.

To alter the cubic zirconia, Dr. Namavar uses a technique

called ion-bombardment, during which he exposes a substance

to a large amount of ions – atoms that have gained an electrical

charge by losing an electron.

Dr. Namavar’s team uses a special ion beam assisted

deposition (IBAD) process to enhance the zirconia’s hardness and

ability to stay wet. They are one of the few research teams at an

academic institituion in the country that uses the IBAD process.

“Utilizing billions of energetic ions as an ionic hammer, we

have forged nano pyramidal structure films possessing combined

properties of super-hardness and complete wetting behavior,” Dr.

Namavar said.

With his coating made of altered pure cubic zirconia, Dr.

Namavar knew he had created a harder, wettable substance that

stands to improve the life of orthopaedic implants.

By altering the hydrophilic (wettability) properties of these

novel materials, Dr. Namavar also created a substance that bones

like to grow on.

Tests done in collaboration with John Jackson, Ph.D.,

associate professor, pathology and microbiology, and Graham

Sharp, Ph.D., professor, genetics, cell biology and anatomy, have

shown that bone stem cells actually attach to and grow on Dr.

Namavar’s coating.

“I knew I had my substance. I thought, ‘here is a material that could be hard and also seems to be able to stay wet.’ ”FEREyDoon nAMAvAR, Sc.D.

AtoMic FoRcE MicRoScoPy iMAgE oF cuBic ziRconiA Showing PyRAMiDAl nAnoStRuctuRES with SizES

RAnging FRoM 130 to 210 nAnoMEtERS.

UNMC discover �

“It seems that our pyramidal nano-structures have a charge

distribution, which the cells find hospitable,” he said. “This was an

unexpected development and one we were thrilled to encounter.”

Dr. Namavar and his team plan to do tests on animal models.

“We hope this leads to prolonged life of orthopaedic

implants and fewer revision surgeries due to reduced friction

and wear of the implant, as well as enhanced bone growth,” Dr.

Namavar said.

Dr. Namavar said his work has been aided by strong

support from Kevin Garvin, M.D., chairman of the department

of orthopaedic surgery, and Hani Haider, Ph.D., an associate

professor of orthopaedic surgery.

Collaborations have been important to his work, Dr. Namavar

said. A grant from the Nebraska Research Initiative has allowed

him to work with Barry Li Cheung, Ph.D., of the chemistry

department at the University of Nebraska-Lincoln, and Renat

Sabirianov, Ph.D., and Wai-Ning Mei, Ph.D., of the physics

department of the University of Nebraska at Omaha.

Dr. Garvin said Dr. Namavar’s coating could prove particularly

important as the health care system faces a surge in the elderly

population, which will lead to more implant surgeries.

“By making implants last longer, this coating could make life

better for patients and physicians alike,” Dr. Garvin said.

“Patients, of course, may be able to avoid the discomfort and

inconvenience of multiple surgeries, which also would take stress

off a system that already is overburdened.”

“We hope this leads to prolonged life of orthopaedic implants and fewer revision surgeries due to reduced friction and wear of the implant, as well as enhanced bone growth.”FEREyDoon nAMAvAR, Sc.D.

thoMAS guStAFSon, intERn, PREPARES thE ion BEAMS ASSiStED DEPoSition (iBAD) SyStEM thAt PRoDucES thE nAnocRyStAllinE coAting.

� fall 2008

it’s easy to be apathetic. it’s something we all experience. some days we just wake up and have no motivation. nothing seems to matter.

however, in some chronic diseases apathy turns into a clinical syndrome characterized by poor initiation, loss of motivation, indifference and lack of persistence.

Apathy syndrome impairs self-management behaviors, leads to functional decline, poor compliance with treatment and generally poor outcomes in chronic diseases.

that’s why two UnMc physicians – prasad padala, M.d., and cyrus desouza, M.d. – zeroed in on apathy as one of the key culprits in patients with Alzheimer’s disease and chronic conditions such as diabetes and obesity.

dr. padala, assistant professor, psychiatry, and dr. desouza, associate professor, endocrinology, also hold appointments at the omaha division - VA nebraska-Western iowa health care system. dr. padala has two grants to study the connection between apathy and Alzheimer’s

ap-a-thy, n., 1. lack of emotion. 2. lack of interest; listless condition; indifference.

apathyWhy should you care?

by TOM O’CONNOR

UNMC discover �

disease. dr. desouza’s grants focus on the impact of apathy treatment in people who are obese. they also have two federal grants that are under review.

the two researchers are studying a well-known drug – ritalin – as a treatment for apathy. yes, the same ritalin that is used to slow hyperactive children.

“ritalin works differently in adults and children,” dr. padala said. “With adults, it gives them more energy. simply put, it increases the dopamine in the brain.”

dopamine is like the gas in your car. Low dopamine levels in the front of the brain can lead to apathy.

“Apathy is one of the most profound and disabling aspects of Alzheimer’s disease,” said William burke, M.d., professor and vice chairman of the UnMc department of psychiatry.

one study determined that apathetic persons are nearly three times more likely than those without apathy to be impaired in day-to-day activities such as dressing, bathing, walking, eating and using the toilet.

in addition, apathy is linked to cognitive dysfunction in dementia patients. With no interest or motivation, it becomes difficult for these patients to use their remaining cognitive function. their memory, learning and communication skills deteriorate.

“people are getting excited about apathy now because it may be a behavioral marker for a more rapidly progressing

dementia,” dr. padala said. “Apathy is considered an untapped behavioral problem. if treated well, it can have significant impact on management of dementia and diabetes.”

dr. padala is conducting a VA-funded placebo-controlled study for apathy treatment in 60 veterans with Alzheimer’s dementia. he said that early study results have been promising, as illustrated by the comments from the wife of an Alzheimer’s patient who is taking ritalin.

“After one month in the study, she came to me and said, ‘thank you for giving my husband back to me. he’s doing things that he hasn’t done in the last five years,” dr. padala said.

diabetes is a major public health problem in the United states. it is much more common among veterans than in the general population. self-management is a critical component to treating diabetes.

“the key to living with diabetes is disease management,” dr. desouza said. “you have to exercise, watch your diet closely, keep your weight down and continually monitor your blood sugars. it’s not easy. you have to be driven.

“Apathy can be devastating for patients with diabetes. once they lose interest and stop managing the disease, the health ramifications can be dramatic,” he said.

dr. desouza knows how difficult it is to motivate patients with diabetes. despite all the innovations in treatment and guidelines, only about 10 percent of patients meet the benchmarks for diabetes control (blood sugar, blood pressure and cholesterol).

the use of ritalin is encouraging in the group of study participants, he said.

“however, the brain is very complicated. We don’t know if improvement is due to the neuro chemical reaction resulting from taking ritalin. More research needs to be done.”

ritalin is not the optimal drug, dr. desouza said. Although it does increase dopamine, it also has several side effects, such as sleep disturbances, decreased appetite and increased blood pressure.

“Apathy is considered

an untapped behavioral

problem. if treated well, it can

have significant impact on

management of dementia

and diabetes.” PRASAD PADAlA, M.D.

PRASAD PADAlA, M.D.

� fall 2008

children who are hyperactive receive 80 mg of ritalin as their daily dose. Adults in the studies are given much lower doses of ritalin with Alzheimer’s patients receiving 10 mg and obesity patients receiving 20 mg. the lower dose helps lessen the side effects.

“We need to find a pharmaceutical agent that can impact apathy,” dr. desouza said. “ritalin is the best drug we have right now, but we are hopeful that we can find a better agent.”

dr. desouza has funding to study the impact of treating apathy on weight loss initiatives. through the omaha VA, 125 veterans were enrolled in the pharmacological and non-pharmacological treatments for apathy.

As part of the study, drs. padala and desouza also are investigating a group therapy, “Medical crisis counseling,” for treatment of apathy.

“there seems to be a common thread linking Alzheimer’s disease and diabetes, since people with diabetes are three times more likely to develop Alzheimer’s disease than non-diabetic individuals,” dr. padala said.

Apathy may be that thread. dr. padala recently received funding from the Alzheimer’s Association to improve functional status, quality of life and glycemic control in patients with co-morbid dementia and diabetes.

“this is ground breaking work,” dr. burke said. “they are trying to determine if treating apathy will not only benefit the day-to-day life of people with Alzheimer’s but if it might also have additional medical benefits in improving glucose control and increasing activity levels. this is a completely novel and exciting approach to a number of well known, often intractable, problems.”

SigniFicAnt iMPRovEMEnt in APAthy ScoRES wAS SEEn in thE SuBjEctS with A MEAn DEcREASE oF 20 PointS on thE APAthy ScAlE (P<.0001). MoSt iMPRovEMEnt in APAthy wAS notED At thE FouRth wEEk viSit, Although thE iMPRovEMEnt continuED thRoughout thE StuDy PERioD.

cyRuS DESouzA, M.D.

59

54

49

44

39

34

29

24

BASELINE

CHANGE IN APATHY OVER 12 WEEKS

APA

THY

EVA

LUAT

ION

SC

ALE

4 WEEKS 8 WEEKS 12 WEEKS

Are you apathetic?

If you answer ‘yes’ to any of these questions, you might

suffer from apathy syndrome and should seek more

detailed testing:

Have you lost interest in the world around you?

Are you more difficult to engage in conversation or in doing chores?

Have you lost interest in doing things or in starting new activities?

Are you apathetic or indifferent?

❚

❚

❚

❚

UNMC discover �

Mentor: a trusted friend, counselor, teacher, a more experienced person.

Much like spreading fertilizer on young seedlings, federal grants awarded to two experienced UnMc researchers – peggy Wheelock and Alexander Kabanov – are helping young investigators advance their careers, enhance their education and build their networks through mentoring. here are their stories.

Junior investigator Jenny Wang,

Ph.D., was about to submit her first R01

grant application to the National Institutes

of Health (NIH), and she wanted it to

be perfect.

Fortunately, so did Peggy Wheelock,

Ph.D., who suggested Dr. Wang wait to

submit the grant. Having sat on review

boards, Dr. Wheelock knows what it takes

to write a grant that will pass muster.

That was in June and for the next four

months Dr. Wheelock patiently helped

Dr. Wang re-write and refine her grant

proposal until it was nearly perfect.

“It was the nicest thing anyone could

have done for me,” Dr. Wang said. “Her

support was just the confidence boost I

needed.”

Right up until the last minute Dr.

Wheelock was still asking Dr. Wang if she

wanted her to read it, just one more time.

“I said no, she had already helped

me make it more understandable for the

reviewers,” Dr. Wang said. “Once we had a

draft that she felt was solid, I was completely

comfortable submitting it in October.”

It’s not unheard of for Dr. Wheelock,

professor of oral biology in the UNMC

College of Dentistry, to take time away

from her research to pour over the grant

proposal of a junior investigator. In fact, Dr.

Wheelock spent countless hours reading

and re-reading Dr. Wang’s grant proposal.

Dr. Wang, who came to UNMC last

year from the Roswell Park Cancer

Institute in Buffalo, N.Y., is one of five

junior investigators finding guidance under

Dr. Wheelock’s wing.

The mentoring program is part of

a $10.9 million Centers of Biomedical

Research Excellence (COBRE) grant that

was originally awarded to Dr. Wheelock

in 2003.

Dr. Wheelock also is the director of the

Nebraska Center for Cellular Signaling,

which was established in 2003 with the

UnMc rEsEArchErs MEntor JUnior inVEstigAtors

GrowinG our ownby LISA SPELLMAN

10 fall 2008

initial COBRE funding. The center focuses

on the study of cell signaling and involves

multidisciplinary collaboration between

researchers. Under the grant, Dr. Wheelock

mentors several junior investigators and

oversees the progress of others whom she

has paired with senior researchers.

Researchers from UNMC, the

University of Nebraska-Lincoln and

Creighton University Medical Center lead

five projects within the grant. Each project

involves the study of cellular signaling with

a focus on its role in producing tumors.

The five-year grant was recently

renewed by the National Center for

Research Resources (NCRR), a division of

the NIH, partly due to the success of seven

junior investigators at UNMC who, with the

help of this program, obtained their own

R01 grants from the NIH.

“The grant allows us to bring together

outstanding junior and senior faculty with

similar interests, which greatly enhances

the science knowledge and opportunities

for collaboration,” Dr. Wheelock said.

When they first met, Dr. Wang was

struck by Dr. Wheelock’s warmth and

friendly personality.

“Right away, she asked me how I

was doing and offered to help in any way

she could,” said Dr. Wang, an assistant

professor in the UNMC Eppley Institute.

Colleagues say Dr. Wheelock’s

willingness to help is what has made her

successful as a mentor.

“Dr. Wheelock is approachable. The

junior investigators working with her

know this and are comfortable going to

her,” said Rob Lewis, Ph.D., a professor

in the Eppley Institute. “She will do

everything she can to help her junior

investigators succeed.”

That includes pairing every junior

investigator with two mentors who can

help them navigate the complex world of

grant writing. It also may mean extending

a junior investigator’s funding from the

usual three years to four – to give them

more time to work on their research.

“Dr. Wheelock could buy a lot of fancy

equipment and fund core facilities, but

instead she invests in human capital and

the potential of young investigators,” Dr.

Lewis said.

The nurturing and feeding of seed

money has worked so well, Dr. Wheelock

has another five years to show more results.

“The COBRE grant we received in

2003 helped us strengthen the biomedical

research infrastructure in Nebraska. We’ve

established a multi-disciplinary thematic

center that enhances the research of

young investigators and now we have

seven success stories,” Dr. Wheelock said.

Dr. Wheelock said one objective of the

renewed funding will be to initiate pilot

projects that further encourage and support

collaborative, multi-disciplinary projects.

“Teaching one how to be a successful,

productive scientist is not a trivial task,”

said Paula Turpen, Ph.D., director of

research resources at UNMC.

“The fact that three of the COBRE

mentors (Drs. Wheelock and Lewis

and Keith Johnson, Ph.D.) have been

recognized as UNMC Distinguished

Scientists in the past two years only

confirms the quality of mentors in the

Center for Cell Signaling. There is no doubt

that the seven new NIH-funded junior

faculty will continue to benefit from the

guidance they received while participating

in the COBRE program.”

Steve Caplan, Ph.D., assistant professor,

biochemistry and molecular biology, is one

of the seven researchers who received a

boost from the COBRE grant.

Dr. Caplan joined the grant in 2004 when

Dr. Wheelock selected him for a pilot project.

He was later asked to become a project

leader and was paired with two mentors:

Richard MacDonald, Ph.D., biochemistry

and molecular biology, and Dr. Lewis.

“They taught me how to write better

grants and advised me on where to

submit my application,” Dr. Caplan said.

“Peggy also helped, reading through parts

of my grant proposals and manuscripts.

She sets the tone for the mentorship part

of the grant.”

Dr. Caplan’s area of study is in protein

trafficking – how proteins get from place

to place in the cell. While it is basic

research, he collaborates with other

researchers who study specific protein

receptors and want to better understand

how proteins move around.

Even though he no longer qualifies

as a COBRE project leader, Dr. Caplan

maintains a connection to Dr. Wheelock

and her work. He finds himself in the

nurturing role.

“I try to help out as much as I can with

the new investigators coming in, because

I believe in what Dr. Wheelock is doing,”

Dr. Caplan said.

“She is an incredible role model,

who dedicates a huge amount of time

to mentoring while maintaining her own

lab. She never stops worrying about what

everyone else who is involved with the

grant is doing. She is amazing.”

PEggy whEElock, Ph.D.

Grow • nurture • Support

The Research Project Grant (R01) is the original

and historically oldest grant mechanism used

by the Natiional Institutes of Health. The R01

provides support for health-related research and

development based on the mission of the NIH.

UNMC discover 11

Alexander Kabanov, ph.d., just received $10.6 million and he knows exactly what he’s going to do with it.

the UnMc researcher hopes to save as many lives as he can by finding better ways to treat and cure hypertension, parkinson’s disease and cancer.

he plans to do this through nanomedicine, an emerging area of science that uses small polymeric particles to deliver drugs safely to disease sites.

he has formed a team of highly talented junior investigators whose own complimentary projects will help dr. Kabanov grow a world-class program in nanomedicine. Each of the junior investigators will be paired with mentors, including dr. Kabanov.

“the research projects funded by this grant will one day provide drug therapies to physicians that

target disease without harming the surrounding healthy tissue, which will result in better clinical outcomes for patients,” dr. Kabanov said.

he received a five-year cobrE (centers of biomedical research Excellence) grant award in october from the national center for research resources (ncrr), a part of the national institutes of health (nih).

As the director of the nebraska center for nanomedicine, a part of the regent approved center for drug delivery and nanomedicine, and the parke-davis chair in pharmaceutics in the college of pharmacy at UnMc, dr. Kabanov tried for five years to get the grant.

it was worth the wait.“While working on the grant

proposal, i got to know UnMc and its scientists and administrators much

better, giving me a deeper sense of pride for the institution,” he said. “those years also gave me time to develop myself into a leader and for that i am very grateful.”

GrowinG our own

there are other benefits to having the cobrE grant.

“it allows us to attract the best and brightest scientists to nebraska and develop novel technologies that could contribute to the economy of the state with the help of spin-off companies that would bring the results of the scientific research to public use,” dr. Kabanov said.

not a bad combination, saving lives – and helping the economy.

the cobrE is part of the institutional development Awards

new CoBre Grant to Grow nanomediCine proGram

AlExAnDER kABAnov, Ph.D.

12 fall 2008

(ideA) network created by the nih/ncrr to more equally distribute funding to states that have not traditionally received as much funding. the awards support multidisciplinary centers – each concentrating on one general area of research – that strengthen institutional biomedical research capability and enhance research infrastructure.

“by bridging the research funding gap in ideA states, we are building innovative research teams, leveraging the power of shared resources, and enhancing the science and technology knowledge of the state’s workforce,” said ncrr director barbara M. Alving, M.d.

the cobrE grant will support the research projects of four junior faculty members, all of whom have been paired with an established faculty member, dr. Kabanov said. the grant promotes collaboration among researchers with complementary backgrounds, skills and expertise.

“All four projects focus on how polymer nano systems may be used to enhance the delivery of drugs, inhibit tumor growth, and improve treatment of cancer, neurodegenerative and central nervous system-associated cardiovascular disorders,” dr. Kabanov said.

the grant also will help establish core facilities needed to carry out the objectives of the multidisciplinary collaborative program. the first is a bioimaging core lab that will allow noninvasive diagnostics of neurodegenerative disease. the second will focus on preparation of new nanomaterials and ensure that these materials are safe for human use.

dr. Kabanov has prepared the ground and planted the seeds of research success. this grant provides the fertilizer that he needs to help grow the program.

Ultimately, it is up to dr. Kabanov and his team of researchers to make it thrive.

“it allowS uS to attraCt the BeSt and BriGhteSt SCientiStS to neBraSka and develop novel teChnoloGieS that Could ContriBute to the eConomy of the State.”AlExAnDER kABAnov, Ph.D.

research seedlings

The four young investigators whose projects will be supported through Dr. Kabanov’s COBRE grant are:

projeCt 1:

Principal investigator: Elena V. Batrakova, Ph.D., assistant professor of

pharmaceutical sciences.

Mentor: Howard Gendelman, M.D., chairman, department of pharmacology

and experimental neuroscience; director, Center for Neurovirology and

Neurodegenerative Disorders.

Dr. Batrakova’s project focuses on creating a drug delivery system to treat

Parkinson’s disease using nanozymes and immune cells in the brain as the

delivery agent. Nanozymes are tiny particles consisting of an enzyme in a

protective polymer coat.

projeCt 2:

Principal investigator: Matthew Zimmerman, Ph.D., assistant professor,

cellular and integrative physiology.

Mentor: Irving Zucker, Ph.D., professor and chairman of the cellular and

integrative physiology department.

Dr. Zimmerman’s research project focuses on using antioxidant therapy

and nanozymes to treat hypertension.

projeCt 3:

Principal investigator: Huanyu Dou, Ph.D., assistant professor, pharmacology and

experimental neuroscience.

Mentor: Surinder Batra, Ph.D., professor, biochemistry and molecular biology.

Dr. Dou’s research project focuses on developing a cell-based

nanoformulated anti-tumor therapy that would improve biodistribution of

the drug to the tumor and reduce chemotherapy-induced neurotoxicity.

projeCt 4:

Principal investigator: Joseph Vetro, Ph.D., assistant professor, pharmaceutical

sciences, and Center for Drug Delivery and Nanomedicine.

Mentor: Alexander Kabanov, Ph.D., director, Center for Drug Delivery and Nanomedicine.

Dr. Vetro’s research focuses on inhibiting the growth of cancer tumors by

using specially developed nanocarrierse that disrupt the tumor’s ability to

recruit surrounding blood vessels.

Grow • nurture • Support

UNMC discover 13

TARGETED DElIVERy

by ELIZABETH KUMRU

NEw sysTEM TAxIs DRuGs TO AIlING BONEs

i INNOVATION

i

1� fall 2008

What you are about to read may cause you to brush

your teeth after every meal. You may also want to rinse

your mouth each night with a special mouthwash

created by a UNMC researcher.

The mouthwash, formulated by Dong Wang, Ph.D.,

associate professor of pharmaceutical science in the

UNMC College of Pharmacy, will not only protect

your teeth from harmful plaque, but it also may help

prevent bone loss in the jaw.

UNMC discover 1�

Run your tongue over the back of your teeth. If it feels as if they

are coated with something, that’s biofilm.

Biofilm, or plaque, is a sticky film of bacteria that constantly

forms on the teeth. Food and drink that contain sugar or starch

are converted by the bacteria in plaque to produce acids that

attack tooth enamel. Over time, the enamel breaks down and

cavities form.

It’s difficult for mouthwash to break through plaque. While

brushing takes it away, plaque resumes its cycle of buildup after

brushing is completed.

A polymer chemist by training, Dr. Wang has taken a

commercially available polymer, or macromolecule, and

formulated it into a novel drug delivery system to carry

antimicrobial agents directly to teeth. The U.S. Food and Drug

Administration has approved the polymer as a pharmaceutical

excipient, or drug carrier.

For commercialization, Dr. Wang envisions a mouth rinse

formula that protects teeth from plaque. “The beauty of this

design is the simplicity. All you have to do every night before

bed is to brush your teeth and then rinse your mouth with our

special formula.

“We certainly will look at different flavors. I want something

that’s tasty,” he said.

The mouth is home to some of the most common diseases

known to humans. Besides tooth decay, known to at least one-half

of American children, unchecked plaque can lead to loss of bone

around the teeth (periodontitis). Other diseases that affect the

gums and lining of the mouth, include canker sores, oral herpes or

cold sores and gingivitis.

Although, collectively, it has declined among young children,

tooth decay still can be a problem for individual children, and even

teens and adults. If untreated, this type of decay can infect the

internal structure and ultimately cause loss of the tooth. Nearly 12

percent of the adult population – more than 35 million people in

the United States – lose bone support around their teeth.

At present, Dr. Wang is collaborating with Kenneth Bayles,

Ph.D., professor of pathology and microbiology, and his team to

evaluate the formula against bacteria found in the oral cavity. “This

synergistic effort with Ken’s group is our first test in the real world,”

Dr. Wang said.

Dr. Wang came to UNMC in January 2005 from the University

of Utah where he started his research in targeted drug delivery for

bones and joints.

After his arrival in Omaha, the Beijing native began a

collaboration with Richard Reinhardt, Ph.D., D.D.S., the B.J.

and Ann Moran Professor of Periodontology and co-director of

DR. Dong wAng in hiS lABoRAtoRy in unMc’S collEgE oF PhARMAcy.

1� fall 2008

“THE DElIVERy sysTEM Is sMAll, AGIlE AND DElIVERs DRuGs TO AN ExACT ADDREss IN THE BODy.”

undergraduate periodontics at the UNMC College of Dentistry.

Together, they have designed several systems for oral applications.

One system developed by Drs. Wang and Reinhardt is a bone-

targeting cyclodextrin conjugate that targets and selectively binds to

teeth and bones. The agent delivered can be released slowly over

time, which increases the therapeutic index, or effectiveness, and

overall performance of the agent.

“The major advantage of the invention over the traditional

formulation is that it offers a very simple mechanism of drug

retention in the target area,” Dr. Wang said. To their surprise, a

control study revealed that the carrier itself has some bone-building

effect. Now the team is exploring the possibility of using this

compound to treat osteoporosis.

“This will be a great addition to the tools dentists have to fight

bone loss and tooth decay,” Dr. Reinhardt said.

Dr. Wang’s other research interests include the development of

improved diagnostic and therapeutic systems for diseases such as

rheumatoid arthritis, cancer bone metastasis and osteomyelitis.

For the treatment of rheumatoid arthritis, Dr. Wang says his

polymeric drug delivery system acts like a Mini Cooper in the way it

delivers medications precisely to the destination.

“The delivery system is small, agile and delivers drugs to an

exact address in the body,” he said.

Traditionally, a drug enters the body through a pill or injection

and travels around to fulfill its purpose. But it also goes places it

shouldn’t, which can cause harmful side effects to bones, organs

and tissues.

For people with rheumatoid arthritis (RA), the prescribed

medications can cause such side effects as osteoporosis, nausea,

easy bruising, mouth sores and possible kidney and liver damage.

Dr. Wang’s drug delivery method uses a more efficient approach

with a polymeric structure that could differentiate the healthy and

arthritic joint. By preferentially delivering drugs to the arthritic joint,

the “Mini Cooper” drug carrier would enhance therapeutic efficacy

and potentially reduce side effects.

Dr. Wang’s joint-targeting delivery system for arthritis

treatment is supported by a three-year, $660,000 R01 grant

from the National Institutes of Arthritis and Musculoskeletal and

Diseases. He is collaborating with one of the world’s foremost

RA experts, James O’Dell, M.D., the Larson Professor and vice

chairman of internal medicine, and chief of UNMC’s section of

rheumatology/immunology.

Dong wAng, Ph.D.

UNMC discover 1�

Dr. O’Dell’s seminal contributions to improvements in RA

therapy include his research on combination disease-modifying

anti-rheumatic drugs (DMARD) and the use of tetracyclines as

therapy for RA. Perhaps his best known work is his study of triple

combination DMARD therapy in the treatment of refractory RA

published in the New England Journal of Medicine in 1995.

“Dr. Wang is doing exciting and cutting-edge research that will

help us deliver medicine to sites of inflammation in the body,” Dr.

O’Dell said. “With his system, we also have the ability to image those

sites more clearly. This will allow us to better diagnose and treat

patients with inflammatory arthritis such as RA.”

With RA, people initially are offered glucocorticoid therapy for

their disease. “But, one side effect of those drugs is osteoporosis,”

Dr. Wang said. “With our polymer carrier, the drugs will be delivered

directly to the arthritic joint and provide long-lasting relief – up to

three weeks in animal studies. Potentially, we may use this as a safer

bridging therapy to allow the effects of DMARD therapy to kick in.”

UNeMed Corporation, the marketing and licensing arm for

UNMC, has negotiated with the University of Utah to combine

technology Dr. Wang developed there with his new RA inventions

developed at UNMC. Human trials may begin in two years.

As a creative thinker, Dr. Wang also wants to know how his

drug delivery systems can be used in the treatment of breast and

prostate cancer that has escaped chemotherapy and taken refuge

in the bone.

“With our bone-targeting polymeric delivery system, it is

possible that we can stop bone damage from cancer metastasis

and kill cancer cells in the bone. The bone often provides a safe

hiding place and a launching pad for the spread of cancer to other

organs,” he said.

If it seems that Dr. Wang is everywhere, it’s because he is

eager to explore how his delivery systems can be applied to

other diseases.

James Linder, M.D., president and CEO of UNeMed, said that’s

characteristic of successful researchers.

“The strength of Dr. Wang’s approach is that he pursues

scientific understanding, while keeping an eye on the clinical

problems that require a solution. This is a key attribute of anyone

who does translational research,” Dr. Linder said.

thE MRi PictuRES DEMonStRAtE thE tARgEting oF thE MAcRoMolEculAR DExAMEthASonE PRoDRug to thE AnklE jointS oF thE ARthRitic RAtS (uPPER PAnEl). thE PRoDRug DoES not StAy in thE hEAlthy AniMAl AnD iS quickly clEARED viA uRinAtion (lowER PAnEl).

“THE sTRENGTH Of DR. wANG’s APPROACH Is THAT HE PuRsuEs sCIENTIfIC uNDERsTANDING, wHIlE KEEPING AN EyE ON THE ClINICAl PROBlEMs THAT REquIRE

A sOluTION.” JAMES LINDER, M.D.

on thE lEFt iS A MicRo-coMPutED toMogRAPhy iMAgE oF An ARthRitic RAt tREAtED with thE MAcRoMolEculAR DExAMEthASonE PRoDRug thAt DR. wAng invEntED. thE iMAgE ShowS PRESERvAtion oF thE BonES in thE AnklE joint. thE iMAgE on thE Right ShowS SEvERE DEtERioRAtion oF thE BonE in An ARthRitic RAt thAt wAS not tREAtED.

1� fall 2008

DR. wANG RECOGNIZED On Oct. 23, Dr. Wang was honored as the recipient of UNeMed’s first

Emerging Inventor Award and received a $25,000 innovation grant for unrestricted research from UNeMed during the 2008 Innovation Awards. The Emerging Inventor demonstrates exceptional skill and appreciation for scientific achievements.

Dr. Wang was among dozens of UNMC inventors who were recognized for their new inventions, patents and licensed technologies. UNeMed Corporation, the marketing and licensing arm for UNMC, sponsored the awards.

“Dr. Wang’s research is a promising step in the search for treatment for the joint damage and pain experienced by people who have rheumatoid arthritis. In addition, his other research efforts focus on osteoporosis and are equally as promising as therapeutics,” said Sara Conrad, licensing associate for UNeMed.

Dr. Wang filed eight New Invention Notifications that have resulted in the filing of seven provisional patents and one international patent application covering several variations of the conjugates and their synthesis, Conrad said.

Michael Dixon, Ph.D., vice president and chief operating officer of UNeMed, said Dr. Wang is one of UNMC’s most prolific inventors.

“His inventions have drawn significant interest from both the clinicians and the pharmaceutical industry. His osteoporosis and arthritis technology have great potential to reach the clinic and improve health care,” he said.

Dennis Robinson, Ph.D. chairman of pharmaceutical sciences, UNMC College of Pharmacy, said Dr. Wang is a worthy recipient of UNeMed’s first Emerging Inventor Award.

“Since joining us in 2005, Dr. Wang’s enthusiasm and commitment has enabled him to rapidly establish a research program of outstanding quality and creativity,” he said.

“He continues to build a growing national and international reputation for his research in drug delivery strategies that target bone and joints. Dr. Wang is an excellent scientist with a truly exciting future.”

Dr. Wang also credits his success to the strong support he has

received from his college and department.

Dr. Wang’s drug delivery research is a perfect example of

translational research that bridges the gap between basic science

and the patient, said Courtney Fletcher, Pharm.D., dean of UNMC’s

College of Pharmacy.

“His projects illustrate to the public how their investment in

research at UNMC and the College of Pharmacy can directly

improve human health,” Dr. Fletcher said.

Research that translates into practical use requires a

curious clinician.

“Clinicians know the science and ask questions and asking the

right question is part of the success,” Dr. Wang said. “Physicians

sometimes use different language, so we as researchers need

patience to learn their language. It’s a very humbling experience.

The same also applies to our collaborations with biologists.

“Pharmaceutical research goes nowhere if we don’t have a

clinical problem. The participation of physicians is essential.”

AnklE jointS oF RAtS DEMonStRAtE thE EFFEctivEnESS oF DR. wAng’S DRug DElivERy SyStEM. iMAgE (A) ShowS thE joint tREAtED with An ARthRitiS DRug uSing DR. wAng’S SyStEM iS wEll-PRESERvED, which iS SiMilAR to thE BonE in A hEAlthy RAt (B). whEn An ARthRitic RAt wAS tREAtED without thE SyStEM, thE RAt’S AnklE joint ExPERiEncED SigniFicAnt BonE loSS (c), which iS SiMilAR to An ARthRitic RAt thAt DiD not REcEivE Any tREAtMEnt (D).

xin-Ming liu, Ph.D., RESEARch ASSociAtE, woRkS with DR. wAng on chEMicAl SynthESiS FoR thE DRug DElivERy SyStEM.

WebExtra

More on Dr. wang’s research www.unmc.edu/discover

UNMC discover 1�

diabetes is a difficult disease to manage. it affects the entire body. Management of blood sugar levels through healthy diet and physical activity is critical. Effective management helps patients lower the risks of developing such health problems as kidney disease, heart and blood vessel disease, blindness and neuropathy.

but for millions of uninsured adults, help with management skills and preventive care seem like a luxury.

A team of UnMc college of nursing researchers want to change that paradigm for patients with type 2 diabetes mellitus (t2dM) and health care providers across nebraska. they are studying how the chronic care model can help patients take small incremental steps toward effectively managing their diabetes and other diseases.

“this project will help us determine the effectiveness of our interventions. We know in theory that prevention is good, self-management works and nursing clinics are valuable. now we’re putting all these elements together into one comprehensive care plan,” said susan beidler, ph.d., associate professor, community based health, and director of the Morehead center for nursing practice.

the UnMc team is led by project director teresa barry, ph.d., assistant professor, families and health systems, and dr. beidler, assistant project director. they are in the second year of a five-year, $1.6 million health resources and services Administration (hrsA) grant.

“We want to help empower people with diabetes to manage their disease better through small, achievable steps in lifestyle changes,” dr. barry said. “We find a higher degree

of success if goals are set by the patient rather than the health care provider.”

t2dM is the most common form of diabetes, affecting 95 percent of the 21 million people with diabetes. t2dM also is more prevalent in minorities and the uninsured. Lack of insurance leads to significant disparities in access and quality of care received, dr. barry said.

in the United states, there are 47 million uninsured people. the diabetes rate among uninsured blacks is twice as high as caucasians and three times as high among hispanics, according to the census bureau report: income, poverty, and health insurance coverage in the United states, 2007.

“For individuals who have limited access to health care and other resources, trying to manage a chronic condition such as t2dM creates stress and can lead to depression and feeling powerless to improve their health,” dr. barry said.

Untreated, the disease can lead to severe complications and increased cost to the health care system and patient. “We’re trying to change these outcomes,” dr. beidler said.

the research project tests the effectiveness of a “three pronged” approach to care. it involves enhancing undergraduate and graduate student learning opportunities in caring for patients with chronic conditions, incorporating the latest evidence-based practice guidelines in provider practice, and promoting patients’ ability to manage their diabetes better.

“if we prove this strategy of care is successful, it can be used in every clinic and applied to other chronic diseases,” dr. beidler said.

patients who are eligible to be in the study have limited financial resources and find it difficult to get medication and follow through with their appointments, dr. barry said. often, preventive efforts are not valued because patients don’t feel sick and the long-term implications of the disease are not understood.

the research project uses the UnMc Mobile nursing center as one way that patients with limited access to a

The care connection

by ELIZABETH KUMRU

nursing study examines new model of care for

chronic disease

20 fall 2008

regular health care provider can get referrals for care and free health screening for diabetes and other conditions. this site also gives students an opportunity to work with underserved patients.

study participants in omaha who need follow-up care can get health care services from the UnMc community health center or other local health clinics. participants outside of omaha are referred to a local health care provider for care.

to date, the study has enrolled 42 low-income patients through the UnMc Family health care center, which is part of the community health center at 5155 s. 36th st.

people enrolled in the study are mostly hispanic who have little or no insurance. they are offered education support in English or spanish, group sessions at the clinic, and home visits.

the key component of the study involves the patient using a diabetes action plan. this action plan helps the patient pick a goal they feel they can meet, such as walking two blocks three days a week. the patient and health care provider can talk about the patient’s progress toward their self-management goals, as well as possible barriers or changes to the goals. goal setting, using the action plan, is an ongoing process and successes are acknowledged and celebrated.

so far, 13 people have participated in the home visit program that is conducted through the Ambulatory care community health nursing project.

this project pairs undergraduate public/community health nursing students with a patient or family for education and self-management support in their home environment where day-to-day management issues can be dealt with realistically. When needed, Lucy Zavala, a bilingual medical assistant at the health center, provides interpretative services for the home visits.

the research has shown that home visits have helped gain the trust of patients.

Jan herzog, the project nurse coordinator at the health center, said that behavior changes can be difficult, but home visits reinforce two messages for the patient.

“it says ‘we care about you and your challenges’ and ‘we take your disease seriously,’ ” she said.

research shows that home visits also motivate patients to stick to their self-management plan, Zavala said.

“they know we are coming to visit and they want to show improvement. the patients feel comfortable being taken care of in their own home and it has made a difference in their plan of care. they feel a sense of trust and comfort having someone in their home who can speak their language and understand their culture,” she said.

resources available to assist patients with developing a self-management plan include food models to show correct portion sizes, illustrated booklets on nutrition and cooking and handouts on exercise. plastic foot models are used to demonstrate proper foot care and identify possible complications that may occur.

the team plans to expand the study with other community partners in other college of nursing sites in Lincoln, scottsbluff and Kearney. in addition, drs. barry and beidler are exploring opportunities for interprofessional education and practice with other health care team members.

Ultimately, they hope this model of care will be implemented in health care practices across the state to help patients deal with chronic diseases beyond diabetes.

“then we will truly have established a care connection,” herzog said.

DRS. SuSAn BEiDlER AnD tERESA BARRy ARE StuDying how A chRonic cARE MoDEl cAn hElP PAtiEntS with DiABEtES MAnAgE thEiR DiSEASE.

jAn hERzog, PRojEct nuRSE cooRDinAtoR, AnD lucy zAvAlA, A BilinguAl MEDicAl ASSiStAnt, inSPEct thE DiABEtES Foot MoDElS

thEy uSE FoR PAtiEnt EDucAtion.

UNMC discover 21

determined to make earlier diagnosis a reality by KAREN BURBACH

Pancreatic cancer eludes detection – but not for long

George Watson knows the grim statistics for pancreatic cancer.

One in 76 people will develop pancreatic cancer, according to

the American Cancer Society. Once diagnosed, a person has less

than a 5 percent chance of living more than five years.

Even so, the Chadron (Neb.) State College professor and

private practice attorney is determined to beat the odds.

“When you first get the diagnosis, you think it’s terminal,”

Watson said. “But there is a percentage who overcome it.”

Watson increased his odds for survival by being eligible for the

Whipple procedure (see sidebar).

But, researchers at UNMC’s Eppley Cancer Center, led by Tony

Hollingsworth, Ph.D., want to increase every patient’s odds by

identifying diagnostic markers that detect pancreatic cancer before

symptoms appear and when surgical removal is still possible.

“I’ve dedicated my career to making earlier diagnosis of

pancreatic cancer a reality,” Dr. Hollingsworth said.

Tissue donated by Watson helps Dr. Hollingsworth and the

UNMC team, one of the largest pancreatic cancer research

groups in the country. “Anything I can do that helps in the

diagnosis and treatment is important for the future,” Watson said.

The National Cancer Institute (NCI) funds three pancreatic

cancer programs of excellence – one is at UNMC.

The $5.3 million, five-year Specialized Program of Research

Excellence (SPORE) grant in pancreatic cancer – sought after

by the country’s most prestigious research and medical facilities

– funds translational research.

“The SPORE grant earned by Dr. Hollingsworth and his

colleagues is an outstanding achievement and important milestone

for scientific research at UNMC and the UNMC Eppley Cancer

Center,” said Ken Cowan, M.D., Ph.D., director of the cancer

center. “The National Cancer Institute continues to recognize the

important work being done at the Eppley Cancer Center.”

For Dr. Hollingsworth and his team, there is an unrelenting

drive to learn more about the basic biology of pancreatic cancer

and study new biomarkers that enable them to diagnose

the disease earlier. They also want to better understand the

progression of the disease and develop new therapies that extend

a patient’s life.

“We’re at the cutting-edge of making a difference in people’s

lives,” Dr. Hollingsworth said.

A 6-inch long, spongy organ, the pancreas resembles a pear

on its side and helps the body digest food and regular body sugar

levels. Cancer occurs when cells in the pancreas develop genetic

mutations, which cause cells to grow uncontrollably. Tumors form

as these cells accumulate.

“If we could shut down that process, we could significantly

extend the patient’s life span,” Dr. Hollingsworth said.

Early detection of the disease, however, is a major hurdle.

22 fall 2008

The location of the pancreas, deep in the abdomen, hinders

early discovery of the disease and, unlike mammography, which

provides early detection of breast cancer, there are no screening

tools for pancreatic cancer. By the time tumors are found they

often measure 1 centimeter or more and have metastasized

or spread.

“The disease has to be managed differently,” said UNMC

researcher Surinder Batra, Ph.D. “We need a more systematic

approach with pancreatic cancer because there’s so little time.”

Watson went to the doctor in February for a nagging ache in

his upper stomach. At first, he was treated for acid reflux and

indigestion, but nothing changed.

When he became jaundiced, doctors ordered a flurry of tests.

The ultrasound and CAT scan showed a tumor on the pancreas.

“I didn’t know much about pancreatic cancer, but knew it was

a bad one to get,” Watson said.

Fortunately, the cancer had not spread beyond the pancreas.

Dr. Batra says a simple blood test – one that detects a

protein produced by pancreatic cancer – would help alert

patients to the disease.

An internationally patented biomarker – first identified by

UNMC researchers in 2001 and featured on the April 2007 cover

of the Molecular Cancer Research Journal – shows promise in

the early detection of the disease. Mucin 4, a human gene also

known as MUC4, is associated with the disease progression and

can be found in blood and tissue.

A high level of the biomarker, detected through a cost-

effective blood test, may mean that cancer is in the body.

“MUC4 expression is strongly associated with the lifespan

of patients and could be a new early and specific marker for the

diagnosis and prognosis of pancreatic cancer,” Dr. Batra said.

“About 80 to 90 percent of pancreatic cancer patients have high

levels of MUC4 in tumors, fine needle aspiration biopsies and

blood, which that makes it easy for us to diagnose cancer.”

Preliminary studies of the blood test show promise and a

validation trial, funded by the NIH RO1 and SPORE grants, is

underway. “The results of our trial could help us better manage

the disease, determine who should go to surgery, how we should

treat the patient and how we might stop or decrease expression,”

Dr. Batra said.

MUC4 may not be the only marker, though.

Several of Dr. Hollingsworth’s projects focus on the study of

MUC1, a glycoprotein that scientists believe plays an important

role in the normal function of the pancreas. MUC1, they have

found, interacts with and alters the function of p53, a tumor

suppressor gene.

“We want to study the big questions and understand how the

tumors invade and metastasize so we can understand why the

“We’re at the cutting-edge of making a difference in people’s lives.”tony hollingSwoRth, Ph.D.

tony hollingSwoRth, Ph.D.

UNMC discover 23

SPORE grant spawns many projects

The UNMC Eppley Cancer Center’s pancreatic program receives nearly $15.5 million in external funds, most of which comes from the National Cancer Institute (NCI).

Of that, $5.3 million is part of a competitive five-year Specialized Program of Research Excellence (SPORE) grant in pancreatic cancer.

The SPORE grant compliments the cancer center’s work with the NCI’s Early Detection Research Network (EDRN) and the UNMC-based Pancreatic Cancer Collaborative Registry. It also supports translational research projects, creates a new core in biostatistical support and provides partial support for UNMC’s tissue bank and unique rapid autopsy program.

The EDRN brings together dozens of institutions to evaluate new ways to test for cancer risk and accelerate the translation of biomarker information into clinical use.

The registry, meanwhile, unites at least 12 centers, including Johns Hopkins University, the University of Pittsburgh, Evanston Northwestern Healthcare and the University of Genoa (Italy), with expertise in pancreatic cancer research. The one-of-a-kind, Web-based registry has collected critical information and biological samples from 1,600 patients to develop prevention and treatment strategies.

UNMC’s tissue bank, directed by Julia Bridge, M.D., and its unique rapid autopsy program, which allows cancer patients to donate entire organs, help researchers to study the disease.

“The rapid autopsy program allows us to acquire a large volume of rarely obtained tissues,” said Tony Hollingsworth, Ph.D., who directs the program and the volunteer efforts of more than 30 technicians, students, nurses, residents and faculty members. “The program enables us to undertake many studies that are not otherwise possible.”

disease is so deadly,” Dr. Hollingsworth said. “Patients should have

hope and take comfort in the fact that there are researchers who care.”

Dr. Hollingsworth’s team helped discover MUC1 years ago. Since

then, they have learned that it protects the cell surface and sends

information about the cell surface to the nucleus. That information

will be used to design tumor vaccines and make better diagnostic

tests for pancreatic cancer. Plans already are underway on a clinical

trial of an immunotherapy protocol that induces the patient’s immune

system to recognize or attack the pancreatic cancer tumor – just as if

it was a foreign invader.

Watson’s father, George Watson Sr., had prostate and lung cancer,

but there is no known history of pancreatic cancer in his family.

After the diagnosis, Watson and his wife, Kathleen, decided to

seek treatment eight hours from home at UNMC’s hospital partner,

The Nebraska Medical Center.

“You have to get to a place that deals with pancreatic cancer,” he

said. “We’re fortunate here in Nebraska that we have a place.”

Jean Grem, M.D., a nationally known expert in gastrointestinal

malignancies, explores novel therapeutic approaches in both colon

and pancreatic cancer. She has developed a clinical trial that uses

a patient’s molecular profile to determine the best drug therapy for

metastatic colorectal cancer.

Plans are underway for a clinical trial to determine whether there

is an advantage to using the peptide inhibitor of N-cadherin to reduce

AARon SASSon, M.D.

“Patients should have hope and take comfort in the fact that there are researchers who care.”

tony hollingSwoRth, Ph.D.

2� fall 2008

George Watson was fortunate, in that, his cancer had not spread beyond the pancreas.

That silver lining gave him the only chance for a cure.

“The gold standard is to have the Whipple procedure, if possible,” said the father of three.

Only 15 to 20 percent of pancreatic cancer patients are eligible for surgery and, of those, only 15 to 20 percent live five years, said Aaron Sasson, M.D., associate professor of general surgery at UNMC, and chief of GI surgical oncology.

Prior to surgery, Watson underwent an intensive treatment regiment to shrink the tumor that sat near an artery. The regiment included three months of chemotherapy and radiation therapy under the guidance of Jean Grem, M.D., and Chi Lin, M.D.

On July 8, Dr. Sasson surgically removed the rest of the growth in a Whipple operation.

Dr. Sasson and his team (Drs. Quan Ly and Chandrakanth Are) are specialists with advanced training in the management of pancreas and hepatobiliary malignancies.

His team takes an intensive approach to surgery, often removing blood vessels that surround the pancreas in order to eradicate the tumor. “Surgery can be quite complicated and last five to seven hours,” Dr. Sasson said.

In the Whipple operation, the head of the pancreas, a portion of the bile duct, the gallbladder and the small intestine is removed. A portion of the stomach also may be removed. Then, the remaining pancreas, bile duct and intestine are sutured back into the intestine.

To ensure the best outcome, the American Cancer Society recommends the Whipple operation be performed in experienced centers, such as The Nebraska Medical Center, that do a high volume of these complex surgical procedures. Dr. Sasson and his team perform more than 50 pancreas operations each year, the majority being Whipples.

The death rate is significantly lower in hospitals that perform a high volume of these procedures, Dr. Sasson said.

“Everything, so far, is good,” Watson said, later during a four-week cycle of chemotherapy. “The prognosis is only as good as the next test.”

Whipple procedure gives hope to people with pancreatic cancer

the growth and spread of tumors and the incidence of metastasis. UNMC researchers

have evidence that expression of N-cadherin by human cancer cells results in tumors

that are highly aggressive. The peptide inhibitor, however, has reduced the severity of

tumors in mice, said UNMC researcher Keith Johnson, Ph.D., who works on the project

with Peggy Wheelock, Ph.D., and Dr. Grem.

Another clinical trial will study the effects of a telomerase inhibitor at three levels: in

cultured pancreatic cancer cells, in mice bearing pancreatic tumors and in patients with

advanced pancreatic cancer.

In cancer cells, an enzyme called telomerase prevents the protective caps at the end

of chromosomes, or telomeres, from shortening, which, in normal cells, naturally occurs

as we age. Once telomeres get too short, a healthy human cell stops dividing. Cancer

cells are immortal, said UNMC researcher Michel Ouellette, Ph.D., because they tend to

express telomerase, which prevents the shortening process and allows malignant cells

to grow out of control. Researchers hope the telomerase inhibitor limits the lifespan of

cancer cells and blocks the regrowth of residual disease after conventional therapy.

That’s the type of news patients like Watson want to hear.

Cancer treatments forced Watson – for the first time in 33 years – to miss this past

summer’s student excursion to London. During his career, he has taken more than 800

Chadron State College students abroad on international study programs.

“The trips give students a different perspective of life in general,” he said.

Cancer does the same.

“The diagnosis changes the reality of your life almost immediately,” Watson said. “I

have tried to take the outlook that cancer should not alter my life plans, but it does make

you more aware of the things that are important and the things that are peripheral.”

SuRinDER BAtRA, Ph.D.

UNMC discover 2�

With many patients, the goal is to get them to function as normal as possible

under the microscope

Susan Swindells, M.D., diagnosed common illnesses and

injuries in an indigent, city-run clinic in Columbus, Ohio, when

HIV first emerged in the early 1980s.

“Patients started to turn up with symptoms we didn’t know

about and there was no one to ask,” she said. “At that time, if you

treated three people, you became an expert.”

Thousands of patients later, Dr. Swindells is now an

internationally renowned expert in human immunodeficiency

virus, or HIV, and co-author of the largest study ever conducted to

evaluate commonly used HIV drugs.

The study, which was led by researchers at the University of

Pittsburgh School of Medicine and published in the New England

Journal of Medicine this past summer, confirmed that one of the

most frequently prescribed triple-drug combinations for initial HIV

infection is the most effective for suppressing HIV, but that a two-

drug regimen is comparable.

“The study showed that the triple-drug therapy currently

preferred by clinicians is indeed the most effective treatment

for HIV disease. It also is the simplest treatment regimen as all

three drugs can be given once a day as one pill, compared to

the two-drug regimen that requires seven pills a day. For those

with prescription insurance, this means only one copayment

each month,” said Dr. Swindells, the Terry K. Watanabe Professor

of Internal Medicine in the section of infectious diseases and

medical director of the UNMC HIV Clinic.

Although, the one-a-day, three-drug regimen is preferred,

it doesn’t work with all patients, Dr. Swindells said, including

pregnant women and individuals with viral resistance.

The study focused in part on nucleoside reverse transcriptase

inhibitors (NRTIs), which are one of the first class of HIV drugs

approved by the U.S. Food and Drug Administration. Although

effective and commonly prescribed, NRTIs can produce severe

side effects in some patients.

The study, which included 753 participants at 55 centers,

found that the popular three-drug combination of efavirenz plus

NRTI therapy was more effective at achieving and maintaining

reduction of the virus than another commonly prescribed drug

combination of lopinavir-ritonavir plus NRTI.

Interestingly, a two-drug combination of lopinavir-ritonavir plus

efavirenz had a similar level of effectiveness as each of the triple-

drug regimens that contained NRTIs.

The study was conducted as part of the AIDS Clinical Trials

Group (ACTG) – the largest HIV clinical trials organization in the

world – with funding from the National Institute of Allergy and

Infectious Diseases.

Dr. Swindells, whose main research interests are in

opportunistic infections, is chairwoman of ACTG’s Optimization of

Co-Infection and Co-Morbidity Management Committee.

The Manchester, England native also is involved with an

international research study to determine how best to treat HIV

and tuberculosis.

Unlike some health care workers who looked the other way,

Dr. Swindells embraced the challenges posed by HIV in the

1980s. “When you’re the clinic of last resort it’s difficult to say ‘go

somewhere else’ because there’s nowhere else to go,” she said.

In 2007, the UNMC HIV Clinic served 926 people, including

126 new cases. “We still see a steady trickle of new people – even

in 2008 when we know how not to get HIV,” she said.

But, unlike the early days, there is greater hope for

today’s patients.

“I tell my patients that HIV is a serious, chronic disease similar

to diabetes in that you have to take care of yourself, eat right, take

your medicine and go to the doctor,” she said. “You may develop

some complications, but the chances of living to 60 are good.”

by KAREN BURBACH

clinical researcher co-authors largest study on hiV drugs

2� fall 2008

We concentrate on two key areas: education and public advocacy. For the past eight years we’ve worked to support the efforts and accomplishments of Nebraska-based medical researchers, science educators and young collegiate scientists. In particular, we have advocated for stem cell research, therapies and cures in Nebraska.

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In 2007, philanthropist, Richard Holland helped form Nebraska Coalition for Lifesaving Cures (NCLC). This new organization was made up of business, education, and community leaders who shared the same goals as Nebraskans for Research. The two organizations joined and took the name Nebraska Coalition for Lifesaving Cures.

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who are we?

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