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Transcript
Explor i ng r esearc h at th e
U n iversity of N ebraska M edical C enter
discover
UNMC
an d beyon d...
miniature
surgical robots
explore the
inner human body
Fa l l 20 07
discover
UNMC
Fa l l 2 0 0 7
exploring research at the
construction,
research growth
continue
University of Nebraska Medical Center
and beyond...
We value your opinion and welcome letters to the editor.
Please send your letter to Discover Editor, UNMC,
985230 Nebraska Medical Center, Omaha, NE 681985230. Letters will be verified before they are printed.
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.
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 requests to [email protected]
UNMC enjoys full accreditation (of all its colleges,
programs and sites) by The Higher Learning Commission
and is a member of The North Central Association of
Colleges and Schools, 30 North LaSalle Street, Suite
2400, Chicago, IL, 60602-2504. Phone: 800-6217440 or www.ncahigherlearningcommission.org
The University of Nebraska Medical Center 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
Communications Coordinator
Karen Burbach
contents
As I write this in my laboratory on the eighth floor of the Durham Research
Center, I have the opportunity to watch the growth of its twin, the latest
research facility on campus.
toxins slow molecular
garbage sweepers
The DRC and the new tower together are appropriate symbols of the UNMC
research enterprise, growing steadily before our eyes.
MERIT scientist unlocks secrets of cilia
UNMC research continues to grow during a time of National Institutes of
Health (NIH) famine, thanks to the diligence, hard work and world-class
excellence of our scientists. This issue highlights some of them and their
great work.
gold standard care for
what price?
Study compares top treatments for
rheumatoid arthritis
Joe Sisson, M.D., is one of five UNMC faculty members to receive the
prestigious NIH MERIT award, and the third member of this elite group
who is a physician-scientist. This is a well-deserved honor, indeed. Dr. Sisson
is an outstanding example of the successful physician-scientist in the 21st
century: he is devoted to his patients, nurturing and knowledgeable; and
at the same time, is a sophisticated, creative, basic biological scientist – as
comfortable in the laboratory as he is in the clinic.
Physician researches risks of posttransplant drugs
Design
Sam Vetter, Daake Design
I’m sure you will enjoy this issue as much as I have. I’m proud to be a part of
this research family, and look forward to another great year in 2008.
University of Nebraska collaboration
launches new surgical tools
fall 2007
Thomas H. Rosenquist, Ph.D.
UNMC Vice Chancellor for Research
14
proteins and tigers
and hormones! oh my!
Researcher’s quest to purify proteins may
impact a $36 billion-a-year industry
DNA analyst Mellissa Helligso
uses ultraviolet light to reveal
evidence of a crime.
omaha’s “CSI” unlocks
hidden clues
DNA lab helps put criminals behind bars
under the microscope
Researcher collects data on tiniest patients
Photography
Jim Birrell, Birrell Signature Photography
JoAnn Frederick Photography
Elizabeth Kumru
Bill O’Neill
11
space-age engineering
transforms surgery
During this century of remarkable advances in biomedical technology,
UNMC’s scientists are pioneering work in surgical robotics. One example
you’ll read about here is a brilliant collaboration between a surgeon and an
engineer whose work will further refine the surgical experience, providing
patients speedier recoveries and a reduced rate of infection.
Editor
Elizabeth Kumru
8
traversing a tightrope
of treatment
Dr. Sisson has competition at home for the household research award: his
spouse is Jennifer Larsen, M.D., also a physician-scientist who is highlighted
in this edition. She has an enviable record of accomplishment that includes
winning NIH support during this difficult time of limited funding
opportunities. Her work is an elegant complement to the overall UNMC
organ transplant program, which is one of the biggest, and surely one of the
most successful, in the world.
As a health sciences center, one of our principal roles in society is basic
discovery. But another, equally important role is to harness laboratory
discovery and put it into use for the benefit of mankind. Elliott Bedows, Ph.D.,
and his new protein purification technique illustrates how that process works.
4
on the cover: UNMC and University of
Nebraska-Lincoln make inroads in minimally
invasive robotic surgery.
20
22
27
A boost to his research came earlier this year when Dr.
Sisson, chief of UNMC’s Pulmonary, Critical Care, Sleep
and Allergy Section in the Department of Internal Medicine,
received the prestigious Method to Extend Research In
Time (MERIT) Award from the National Institute on
Alcohol Abuse and Alcoholism (NIAAA) to further study
the stimulation effects of alcohol on airway clearance.
“Dr. Sisson has made
considerable progress
in unraveling the details
by which ethanol
impairs ciliary function.”
Samir Zakhari, Ph.D.
NIAAA Division of Basic Research
The MERIT award – which extends Dr. Sisson’s National
Institutes of Health (NIH) R01 grant from 5 years to 9 years
– allows him to focus on the science without the need to
prepare competitive renewal applications. This increases
his total grant award from $2.5 million to nearly $5 million
over the 9-year period.
toxins slow
molecular
garbage
sweepers
“The magnitude and impact of alcohol-related respiratory
illnesses has not been widely appreciated, nor extensively
studied,” said Samir Zakhari, Ph.D., director, NIAAA
Division of Basic Research. “Dr. Sisson has made
considerable progress in unraveling the details by which
ethanol impairs ciliary function. His research on the effects
of cigarette smoking, alone or in combination with alcohol,
has shown that acetaldehyde (an alcohol metabolite) is a
mediator in the development of lung disease.”
MERIT scientist
unlocks secrets
of cilia
by Karen Burbach
Each day, tiny garbage sweepers go to work to clear a path
in your lungs.
But, it also helped the cilia cinematographer catapult his
research career.
Without fanfare, the workers – hair-like structures inside
the human airways – oscillate 5 to 25 cycles per second to
sweep the path clean.
“Like a speedometer, we could record how fast they
moved, but, back then, we knew little about how they were
regulated,” Dr. Sisson said.
Their round-the-clock diligence keeps pneumonia and
other respiratory diseases at bay by clearing the lung of
mucus and inhaled particles.
Today, the nationally recognized UNMC scientist and his
team are unlocking secrets of how cilia function and are
exploring the effects alcohol, smoke, dust and viruses have
on the tiny hair-like structures.
Joe Sisson, M.D., began videotaping this mobilized army
of cilia 20 years ago. It was tedious work, pointing his
camera at the miniscule, finger-like lining for a rare
glimpse of the synchronized movements that thrust
garbage out of the lung.
fall 2007
“You have to keep your mind open to possible connections
because when you connect the dots, that’s when the
unexpected happens,” Dr. Sisson says.
In studying the stimulation effects of alcohol on cilia,
Dr. Sisson and his research team have discovered that
chronic alcohol intake impairs the mucous clearance by
interrupting enzymes that normally maintain the cilia. As
a result, heavy drinkers are more likely to get pneumonia
than non-drinkers.
Dr. Sisson has always taken things apart. Early on, it
was televisions and lawn mowers in his father’s garage.
Today, it’s cilia inside his lab at the University of Nebraska
Medical Center.
Dr. Sisson was headed for private practice when Guy
Zimmerman, M.D., introduced him to research. The words
of the clinician/researcher at the University of Utah, where
Dr. Sisson did his fellowship in pulmonary and critical care,
still echo in his head: “He looked me in the eye and said
‘you have a chance to discover something no one has ever
seen before.’ ”
“natura maxime miranda in
minimis,” or “nature is greatest
in little things”
In 1987, after a research fellowship at the NIH, Dr. Sisson
and his wife, clinician/researcher Jennifer Larsen, M.D.,
returned to the Midwest. The Iowa natives chose UNMC
because “here we thought we might make a difference,” Dr.
Sisson said.
And he did after Stephen Rennard, M.D., then chief of
pulmonary and critical care, casually said: “You should
think of doing something with cilia.”
In nature, cilia help earthworms expel nitrogen wastes
and enable clams, oysters and mussels to breathe through
curtain-like gills covered with cilia.
In humans, each airway epithelial cell contains about
200 cilia, which, in a coordinated fashion, creates waves
to propel mucus and particles out of the lung, much like
an escalator carries people to different floors. There are
millions of cilia – Latin for “eyelash” – within the trachea
and bronchial tubes. They exist in the ear, eye, brain and
spinal cord and also have a reproductive function – they
help propel eggs down the fallopian tube.
Humans lacking normal cilia function are plagued with
respiratory tract infections, have impaired fertility, get
recurrent ear infections and have other complications
related to dysfunctional cilia motion.
Cilia fascinated Dr. Sisson. “Their motion is gorgeous
– almost like a ballet – and there was little known about
them,” he said.
That didn’t change until the early 1990s when Dr. Sisson
replaced his video camera with an early version of the SissonAmmons Video Analysis (SAVA) system, which he designed
with software engineer Bruce Ammons, Ph.D. “We had to
find an automated way to measure the cilia beat frequency
UNMC
discover
of alcohol stimulates the cilia, but long-term, high-dose use
results in a loss of responsiveness among the cilia.
Once desensitized, or resistant to stimulation, the cilia are
unable to accelerate the removal of mucus and particles
from the lung during stress, thus increasing the risk of
pneumonia or other lung diseases caused by inhalation
such as cigarette smoking or exposure to dusts.
Dr. Sisson and UNMC’s Todd Wyatt, Ph.D., also are
exploring whether cilia can be protected with medication
and if the impact of alcohol in the cilia is reversible. “We
have some intriguing clues that these defects may be
reversible,” Dr. Sisson said.
This image shows four intact ciliated tracheal cells stained
with color-coded antibodies. The critical cilia regulation
enzyme, nitric oxide synthase (green), is located in the basal
The team has approached this problem by examining cilia
at three different levels. At the highest level, where the most
body of each cilium just below the cilia axoneme (red) where
the motor enzymes are located that make cilia beat.
so it didn’t take minutes to do an experiment and weeks to
analyze the data,” Dr. Sisson said. “SAVA let us analyze a day’s
worth of data while we had lunch.”
The system, now used in more than a dozen labs around
the world, enables scientists to record video directly into the
computer to analyze cilia motion.
Dr. Sisson’s research expanded to include the impact
of alcohol on the lung after UNMC professor and
internationally known liver expert Mike Sorrell, M.D,
inquired about the effects of acetaldehyde – a breakdown
product of alcohol – on cilia. As a pulmonologist, Dr. Sisson
was intrigued: acetaldehyde also is a byproduct of smoking.
“It seemed the lung was potentially slammed in more than
one way,” he said.
Dr. Sisson already knew that small quantities of smoke
slow cilia beating, but now he would compare it to another
molecule. “We knew alcoholics have a higher propensity for
pneumonia,” he said. “We wanted to connect the dots and
see if impaired cilia were part of the problem.”
Dr. Sisson was the first to report, 15 years ago, that nitric
oxide is a stimulatory regulator of cilia beating. He has
applied his nitric oxide interest to the field of alcohol
disease and has advanced the study of alcohol effects on
airway clearance.
When cilia are stimulated by alcohol, their coordinated
movements increase – similar to tall grasses blowing in
the wind or the human “wave” at an athletic event – and
they produce more nitric oxide. Short-term, low-dose use
fall 2007
Short-term, low-dose use
of alcohol stimulates
the cilia, but long-term,
high-dose use results in
a loss of responsiveness
among the cilia.
clinically relevant observations can be made, ciliary function
is studied in whole animal. At an intermediate level, cilia
function of individual airway cells is examined in a tissue
culture system where more complex experiments can
be conducted. At the most detailed level, ciliary function
in isolated cilia, which have been removed from their
cell moorings, are studied in a cell-free system. “We have
discovered that nitric oxide is located in the cilia basal at all
three levels, which means the ciliary control mechanism is
intrinsic to the cilium itself,” Dr. Sisson said.
His research with nitric oxide also has prompted studies in
the pulmonary research group on how mechanical vests,
used in the physical therapy treatment of cystic fibrosis, work
and whether the vest stimulates nitric oxide production and
promotes improved mucus clearance from the lung.
Dr. Sisson, who has had continual NIH funding since 1991,
credits Dr. Wyatt for lending a whole new dimension to
his research.
Only a small percentage of investigators
annually are selected to receive the
prestigious Method to Extend Research in
Time (MERIT) Award from the National
Institutes of Health. Dr. Sisson joins a handful
of UNMC colleagues who hold the honor:
Irving Zucker, Ph.D., (1992), Lynell Klassen,
M.D., (2000), Howard Gendelman, M.D.,
(2001), and Michael Brattain, Ph.D., (2001).
“Focusing on the combination of cigarette smoke and alcohol
is novel,” said Dr. Wyatt, associate professor in UNMC’s
Pulmonary, Critical Care, Sleep & Allergy Section, noting that
UNMC, along with Louisiana State University and Emory
University, are the only three major alcohol study groups
focusing on the lung in the United States.
The pair began studying the effects of the two social ills,
Dr. Wyatt said, based on observations that more than 95
percent of alcoholics smoke cigarettes and between 30 and
50 percent of all cigarette smokers are problem alcohol
users. “So many models of the impact of cigarette smoking
on the lung for the past 50 years have focused entirely on
the exposure of cigarette smoke and have really ignored
alcohol,” Dr. Wyatt said.
Researchers know that alcohol alters the critical proteins, or
kinases, that regulate cell functions in cilia. But, Drs. Sisson
and Wyatt want to know how that occurs, how long it
persists if alcohol is removed and the combined impact of
smoking and alcohol, on airway kinases.
Based on the team’s animal model and tissue culture
studies, there is a clear double whammy when alcohol and
cigarette smoke are combined, Dr. Wyatt said.
In the lung, chronic use of alcohol prevents the
stimulation of increased cilia beating and enhanced
clearance by blocking the activation of a specific enzyme,
cAMP-dependent protein kinase. Cigarette smoking, in
combination with alcohol consumption, activates another
enzyme, protein kinase C, which directly slows cilia beating.
“The combined inhibition of a stimulatory kinase and
activation of an inhibitory kinase produces a unique ‘twohit’ disruption of normal cilia beat,” Dr.Wyatt said.
As a result, Dr. Wyatt says smoking bans in bars and
restaurants are advantageous to public health. “Our
research suggests that no amount of the combination of
smoke and alcohol can be good for the lung,” he said.
Dr. Sisson’s video days may be behind him, but not his
enthusiasm to better understand the actions and reactions
of cilia. “When you get into interesting science you want
to take the engine apart and find out what’s inside the
transmission,” he said, setting aside the black marker he’s
used to illustrate cilia, his cinematic stars.
The promise of basic science, he said, is helping patients with
disease prevention and developing better drug therapies.
“As a clinician, I want to connect the dots between the basic
science and clinical worlds and learn how to detect, prevent
and treat cilia disorders in patients who have lung disease,
especially those affected by smoking and alcohol.”
UNMC
discover
The drugs
by Elizabeth Kumru
Gold Standard Care
for what price?
Study compares top treatments for rheumatoid arthritis
The best treatment
for the best price.
But the answer could save millions of
dollars every year for patients and the
government.
All patients want that, but when
rheumatologists have a choice between
two effective “gold standard” treatments,
one costing 15 times more than the other,
the options blur.
Dr. O’Dell initially turned to the
manufacturers for answers, but
pharmaceutical companies have little
incentive to compare one treatment to a
less expensive therapy. Additionally, the
Food and Drug Administration has never
required these comparisons.
UNMC’s James O’Dell, M.D., and
rheumatologists from around the
world want to know which medication
can provide the best care at the most
economical price.
Dr. O’Dell, professor of internal medicine
and chief of the rheumatology and
immunology section, began pondering
this question eight years ago.
It’s a question the pharmaceutical companies
didn’t necessarily want answered.
fall 2007
Frustrated, he designed a first-of-its-kind
comprehensive $13 million study that
will enroll 600 patients from 35 clinics
and medical centers in the United States
and Canada. The study, funded by
Veterans Affairs (VA) and the Canadian
Institute of Health Research, began in
July and is expected to take nearly three
years to complete.
Most rheumatoid arthritis studies have an
80 percent concentration of women, but
because many patients will be enrolled
through the VA, the study will have equal
numbers of men and women.
The study, which took four years to
develop, is called RACAT (pronounced
rocket), an acronym for “Rheumatoid
Arthritis: Comparison of Active Therapies.”
The random, double-blind study
compares two therapies:
+ A combination of methotrexate,
hydroxychloroquine and
sulfasalazine, which costs patients
approximately $1,000 a year, to
+ A combination of methotrexate and
etanercept which costs patients
approximately $15,000 a year.
Methotrexate, an immune suppression drug, has gained
popularity among doctors as an initial disease modifying
anti-rheumatic drug (DMARD) because of its effectiveness
and relatively infrequent side effects.
Hydroxychloroquine, an anti-malarial drug, is considered a
DMARD because it can decrease the pain and swelling of
arthritis as well as possibly prevent joint damage and reduce
the risk of long-term disability.
Patients in the study will take one
combination of drugs for 24 weeks. If,
after that time, there is no improvement,
they will be switched to the other
combination for 24 weeks.
Taking the study a step further, Dr.
O’Dell also will determine what role
genetics play in the different treatments,
or who responds better to which drug
combination.
“We’ll look for genetic factors and
biomarkers that predict disease
progression and success or toxicity of the
different strategies,” Dr. O’Dell said.
“Early treatment is the key to successfully
managing this disease,” he said. “Our
hope is that one day doctors will be able
to prescribe the most effective treatment
for their patients based on genetics. That
will eliminate a lot of experimenting.”
More than 660 million people in the
world, including 2 million in the United
States, suffer from rheumatoid arthritis.
The autoimmune disease causes chronic
inflammation of the joints and other areas
of the body, and affects people of all
ages. Researchers have not been able
to determine a cause or a cure for the
disease, but treatments are available, with
a goal of remission or near remission.
Sulfasalazine, an oral medication traditionally used to treat
inflammatory bowel diseases, is used to treat rheumatoid
arthritis in combination with anti-inflammatory medications.
Etanercept is a biologic medication that binds a protein in the
circulation and in the joints that causes inflammation before
it can act on its natural receptor to “switch on” inflammation.
This effectively blocks the tumor necrosis factor inflammation
messenger from calling out to the cells of inflammation.
Methotrexate alone is an excellent,
economical first-line therapy for a
significant percentage of rheumatoid
arthritis patients, Dr. O’Dell said. However,
combination therapy is recommended
for those patients who continue to
have disease flares, which can result in
permanent joint destruction.
The group established a serum, plasma,
urine and blood bank for investigational
purposes. Dr. O’Dell’s original observations
of genetic predictors were the first of their
kind and have altered the way patients
are treated. The current study brings
together an impressive coalition of public
and private health centers across two
In a 1996 study, Dr. O’Dell proved that
triple therapy, a combination of three
drugs – methotrexate, sulfasalazine and
hydroxychloroquine – was 50 percent
more effective in treating rheumatoid
arthritis than methotrexate alone or
the combination of sulfasalazine and
hydroxychloroquine.
That study was conducted through the
Rheumatoid Arthritis Investigational
Network (RAIN), a group of
rheumatologists and nurse-study
coordinators in several states across
the country. Dr. O’Dell founded
RAIN in 1989; its
home base is
at UNMC.
UNMC
discover
“This is an exciting, groundbreaking
study that will answer important
questions about the effective and
economical treatments for patients
with rheumatoid arthritis.”
David Daikh, M.D., Ph.D.
University of California-San Francisco
countries. In addition to the 10 sites in
the RAIN network, Dr. O’Dell recruited
15 Veterans Affairs Medical Centers and
10 Canadian Rheumatology Research
Consortium (CRRC) sites.
One of those sites, the San Francisco
VA Medical Center, is slated to enroll 20
patients, said David Daikh, M.D., Ph.D.,
chief of rheumatology at the VA center,
and associate professor of medicine at the
University of California-San Francisco.
“This is an exciting, groundbreaking
study that will answer important questions
about the effective and economical
treatments for patients with rheumatoid
arthritis. As we gain more understanding
about the disease and more therapies
are developed, we can begin to turn
our attention to the next big frontier of
targeting therapeutics. That’s where the
genetic data will be helpful,” he said.
The VA and CRRC now spend more than
$50 million every year on these expensive
therapies and are very interested in the
results of this study, Dr. O’Dell said.
Traversing a
tightrope of
treatment
by Lisa Spellman
“I think clinicians around the world
will use this information to make better
judgments for their patients who have
rheumatoid arthritis,” he said.
Rheumatoid arthritis registry
fills important niche
by Chuck Brown
A registry created by Nebraska researchers and
containing information about military veterans
with rheumatoid arthritis may offer important
insights into male rheumatoid arthritis sufferers.
“The veterans registry allows researchers
to examine specific medical and biological
information about hundreds of male rheumatoid
arthritis suffers to see what genetic and
environmental factors may have played a role in
the patients’ disease,” said Ted Mikuls, M.D., an
associate professor of rheumatology at UNMC who
oversees the registry.
Rheumatoid arthritis often affects women
between 20 and 50 years of age. Men are usually
affected later in life.
“While fewer males may suffer from rheumatoid
arthritis, they still compose a significant portion
of the population with the disease,” said Dr.
Mikuls, who also serves as a rheumatologist
with the VA Nebraska-Western Iowa Health Care
System. “Because the veteran population is so
overwhelmingly male, we are in a special position
to gather information about men suffering from
the disease.”
10
fall 2007
Males account for more than 90 percent of the
roughly 900 veterans with information in the
Veterans Affairs Rheumatoid Arthritis registry
(VARA ) – making it perhaps the nation’s top
source of information about male rheumatoid
arthritis sufferers, Dr. Mikuls said.
Dr. Mikuls and Amy Canella, M.D., an assistant
professor of rheumatology at UNMC who also
works at the Omaha VA, started VARA in 2002.
VA medical centers in Omaha, Denver, Dallas,
Washington, D.C., and Salt Lake City contribute
information to the database. More centers are
expected to join the registry.
Leading rheumatoid arthritis scientists from
around the nation, including Peter Gregersen,
M.D., of The Feinstein Institute for Medical
Research in Manhasset, N.Y., and James
O’Dell, M.D., chief of UNMC’s rheumatology and
immunology section, have expressed interest in
the data collected in VARA.
“You don’t usually find such a well-defined
cohort,” said Dr. Gregersen, who has led the
world’s largest effort to identify the genes
involved in rheumatoid arthritis.
Ted Mikuls, M.D.
Dr. Gregersen has mined hundreds of millions of
genotypes from VARA that he plans to use in his
research.
Being able to look at such a specified group of
rheumatoid arthritis sufferers may offer insight
into how genetic and environmental factors play
into the cause of rheumatoid arthritis, he said.
VARA is a truly unique and powerful resource
thanks to the combination of a well defined
clinical cohort with radiographic data, serological
studies, DNA information and banked biological
material, Dr. O’Dell said.
“VARA is certain to teach us much about
rheumatoid arthritis for years to come,” he said.
Kea Huq knew
it would be a
balancing act
after her kidney
transplant in 2004.
On one hand she felt better than she
had in years, on the other she would
forever be forced to take powerful
medications to keep her body from
rejecting the donated organ.
One risk she didn’t count on was
developing diabetes because of those
medications.
With more than 97,000 people on the
waiting list for an organ transplant, Huq
(pronounced ‘Huk’) considered herself
lucky to receive a new kidney.
UNMC
discover
11
“While genetics probably plays
a role in the development
of diabetes after transplant,
immunosuppressant drugs may
push individuals at risk over
the edge if they can cause
insulin resistance, too.”
UNMC seeks national recognition
as ‘bench to bedside’ leader
Kea Huq
Jennifer Larsen, M.D.
“I was so glad to be alive,” Huq said. But, her happiness
would turn into anxiety a year after her transplant when
the Douglas County Hospital charge nurse was diagnosed
with diabetes.
Roughly 25 percent of transplant patients develop diabetes
after their life-saving operation.
Jennifer Larsen, M.D., associate dean for clinical research at
UNMC, is working to prevent this treatment complication.
In 2006, Dr. Larsen published a study in the journal
“Transplantation” that provides evidence to support her
theory that the immunosuppressant drugs tacrolimus
and sirolimus, known by the trade names Prograf® and
Rapamune®, cause insulin resistance.
“It was widely believed that corticosteroids, such as
prednisone, one of the most common anti-rejection drugs,
was the main cause of insulin resistance and diabetes after
a transplant.
“Considerable effort was made to find immune
suppressant regimens that didn’t require corticosteroids
that would still be as effective. Often those regimens
included tacrolimus or sirolimus, but post-transplant
diabetes wasn’t reduced,” she said.
Dr. Larsen began to wonder if these two immunosuppressants could be the culprit and in 2004 began testing
her theory in male rats.
“After just two weeks of daily injections of either drug, the
normal rats began to have elevated blood sugars,” she said.
More importantly, Dr. Larsen discovered that treatment with
sirolimus resulted in higher blood insulin levels, even more
than the tacrolimus.
“This is similar to what occurs with insulin resistance that
leads to type 2 diabetes,” she said.
12
fall 2007
Now, Dr. Larsen wants to understand how these two
important anti-rejection medications cause insulin resistance.
patients before and after they receive a kidney, pancreas or
islet cell transplant.
“If we can discover the mechanism, maybe we can tailor
new immune suppressant drugs that are less likely to
cause diabetes or develop therapies to prevent diabetes in
transplant patients,” she said.
Patients who receive a kidney, pancreas or islet cell transplant
are screened for elevated glucose levels at every visit – at least
four times the first year following their transplant and at least
once a year thereafter.
Huq, who received her transplant at the Mayo Clinic in
Minneapolis, appreciates Dr. Larsen’s commitment to
finding a way to prevent diabetes in people who already
have gone through so much.
Dr. Larsen credits James Lane, M.D., an endocrinologist at UNMC
who works closely with the transplant team, with discovering that
if transplant patients are going to develop diabetes, they are most
likely to develop it in the first year after their transplant.
“These anti-rejection medications are so powerful, I wish
more doctors would be careful,” Huq said.
And so it was for Huq, who began to notice her blood
sugar numbers rise within the first few months after her
kidney transplant.
But without the medication Huq’s body would reject the
new organ.
While post-transplant diabetes can occur after any
transplant, the current numbers are generally lower after a
liver or heart transplant than after a kidney transplant, Dr.
Larsen said.
Many factors contribute to these differences, such as
the age at which the individual has the transplant, their
individual risk factors for developing diabetes, such as
weight and family history, as well as which medications are
used, she said.
“While genetics probably plays a role in the development
of diabetes after transplant, immunosuppressant drugs
may push individuals at risk over the edge if they can cause
insulin resistance, too,” Dr. Larsen said.
“When I first noticed it my blood sugar was 120,” she said.
“My doctors suggested I change my diet to try to control it,
but it continued to rise.”
Normal fasting blood sugar is less than 100. Fasting blood
sugars between 100 and 125 are now recognized to represent
pre-diabetes, which suggests diabetes could be developing
and fasting blood sugars of 126 or greater is the level at which
diabetes is diagnosed.
When her blood sugar hit 160, Huq sought out a doctor
closer to home to help control her blood sugar.
Huq is now followed by Dr. Lane. She has her lab work done
at UNMC and sent to her doctors at the Mayo Clinic.
So far, Huq only has had to take medications to help control
her diabetes.
And patients who develop insulin resistance and diabetes
after transplant seem to require insulin for treatment sooner
than individuals who develop diabetes who’ve never had a
transplant.
While she has not had the easiest time since her transplant,
Huq said she would do it all over again if she had to, with
one exception.
That’s why Dr. Larsen and other diabetes physicians work
closely with the transplant team at UNMC to evaluate
“I would want to know more about the medications and talk
to the doctors about trying to find the best combination so
that, hopefully, I wouldn’t develop diabetes,” she said.
UNMC is striving to become a national leader in clinical and
translational research in the areas of cancer, transplantation,
biopreparedness and neurosciences. The academic medical center
hopes to secure one of the 60 Clinical and Translational Science
Awards (CTSA) from the National Institutes of Health.
In November, the NU Board of Regents approved the establishment
of the Center for Clinical and Translational Research in an attempt
to strengthen the pending application. UNMC plans to apply for
the CTSA award in October 2008.
The comprehensive center will provide an administrative structure,
improved training, space and core facilities to support clinical
and translational research across all four UNMC campuses.
Collaborations with underserved communities also will be developed.
The advent of this new award is part of a national movement to
create a stronger health care system by transforming clinical and
translational research at academic health centers across the country.
NIH officials created the awards to increase collaboration between
researchers from differing disciplines, making the translation of
research from bench to bedside more efficient.
Improved interactions between scientists, clinical practitioners,
behavioral specialists, biostatisticians, epidemiologists, bioengineers,
pharmacologists, medical economists, community members and
patients may be key to solving medical mysteries, said Jennifer Larsen,
M.D., associate dean for clinical research, UNMC College of Medicine.
Dr. Larsen said UNMC hopes to receive a CTSA by the time the
award process is finalized in 2012. In preparing to apply for a CTSA,
Dr. Larsen’s team has been re-evaluating UNMC’s clinical and
translational research enterprise. Some of the new developments
out of this process include the initiation of a new research-training
track that allows different health care professionals to learn
the latest clinical and translational research technology side-byside. Other developments include a universitywide clinical and
translational research seminar for both clinicians and basic scientists
and exploring new ways that investigators with common research
interests can meet and collaborate.
“UNMC has many resources in place that make securing a CTSA
possible,” Dr. Larsen said, “including new research facilities, multiple
areas of established translational research expertise, an electronic
medical record and considerable expertise in the areas of health
informatics and bioinformatics.” Even so, she said, there is much left
to do to improve collaborations across disciplines, as well as with
neighboring institutions.
UNMC
discover
13
Space-age
engineering
transforms
surgery
by Chuck Brown
Technology that enables robots
to explore the rocky and
formidable terrain of Mars
is being adapted to explore
another new frontier – the
inner human body.
Dr. Farritor – a native of Ravenna, Neb., and a 1992 UNL
graduate – had helped make waves around the, well,
galaxy for his contributions to the Mars Rovers.
UNMC’s Dmitry Oleynikov, M.D., and UNL’s Shane Farritor,
Ph.D., met during a spring 2002 research retreat and
proposal contest designed by the vice chancellors of the
two schools to encourage cross-disciplinary cooperation
among scientists from each campus.
Before returning to his alma mater in 1998, he worked in
the Massachusetts Institute of Technology Field and Space
Robotics Laboratory and the Unmanned Vehicle Lab at
the C.S. Draper Laboratories in Cambridge, Mass. He also
studied at the Kennedy Space Center in Florida and the Jet
Propulsion Laboratory in Pasadena, Calif.
“Number three on the list was miniature surgical robots
inside the body,” Dr. Farritor said. “I like to joke with Dmitry
14
fall 2007
Dr. Oleynikov had just been recruited from the University
of Washington by UNMC Surgery Department Chairman
Byers “Bud” Shaw, M.D., to raise the medical center’s
profile in the world of advanced surgical technology.
So it seems fate clearly intervened five years ago when
a UNMC surgeon introduced himself to a University of
Nebraska-Lincoln engineer with ties to NASA, launching a
collaboration that is revolutionizing surgery.
After their initial meeting, Dr. Oleynikov gave Dr. Farritor a list
of five ideas they could explore for their research proposal.
Dmitry Oleynikov, M.D.
that his other four ideas were horrible – but he was onto
something with the robots.”
Together, their mini robot project captured the imaginations
of the vice chancellors for research and received an award
that came with $60,000 in project funding.
Shane Farritor, Ph.D.
UNMC
discover
15
Dr. Farritor displays two of the surgical robots he and Dr.
Oleynikov have developed. On the left is a mobile camera robot
that can move around inside of a body cavity and provide images
to surgeons. The robot on the right is the ceiling pan/tilt robotic
camera which provides a bird’s-eye view of the surgical site.
Even before coming to UNMC, Dr. Oleynikov was interested
in surgical robots.
“We realized we had a special opportunity and we were
determined to make something happen,” Morien said.
At the time, the world’s most advanced robotic surgical
solution was Intuitive Surgical’s da Vinci® Surgical System
– a large robot that mimics a surgeon’s hand movements
during an operation and is able to negate potential hand
tremors that can hinder surgery.
She recalls one other aspect of the lunch as well.
UNMC was the eighth medical center in the country to
acquire the da Vinci system – putting UNMC on the map in
the area of computer-assisted surgery.
While the da Vinci enables more complex procedures to
be performed on a minimally invasive approach, it doesn’t
remedy some of the major obstacles of laparoscopic
surgery, in particular limited range and motion of the scope
cameras and lights that enter a patient’s body through a
small incision.
“The scopes can only move so much because we don’t
want to make the incision larger, so it makes it hard to
see everything around the area we are operating on,” Dr.
Oleynikov said.
“I remember picking up the bill,” she joked.
Dr. Farritor was as intrigued by the idea of making robots
that could navigate the body’s inner organs as he was in
designing robots that traveled the surface of Mars.
“In reality, the robotic concepts used to get robots to
move on Mars or in the body are the same,” Dr. Farritor
said. “Both are ‘remote environments’ where the robot is
operating in a strange place.
“This brings with it a lot of engineering challenges, such
as how the robot is controlled, what sensor information is
needed and how decisions are made.
“We were trying to make a robot that would drive around
on the organs while not causing damage,” Dr. Farritor said.
“The environment is delicate, soft and slick and you don’t
want to get stuck.”
As they moved into development, Dr. Farritor observed Dr.
Oleynikov performing surgery to get a better understanding
of what he was looking for in the robots and what issues
surgeons face in their work.
The team experienced some challenges in getting the
robots to where they could move across certain organs,
Morien said.
”Surfaces are different depending on the organ,” Morien
said. “The gall bladder is different from the liver, which is
different from the bowel. Our robots had to be able to roll
on all of them.”
Within a year of their Cajun meal, the team had a
prototype developed.
Drs. Oleynikov and Farritor have since designed a suite of
robots, all about the size of a lipstick case. Some robots
carry lights, others carry cameras and one is even capable
of performing a biopsy.
They are all controlled through a computer, meaning
surgeons can operate the robots from hundreds of miles
away. This aspect made the robots attractive to the U.S.
To remedy this, Dr. Oleynikov began thinking small –
really small.
He envisioned tiny robots the size of a lipstick case that
could be placed in a patient’s abdominal cavity and move
around in a patient’s body. Armed with cameras, lights and
other tools, robots could provide surgeons with a much
greater range of operation, he thought.
One of hundreds of sketches the
team drafted in the development of
miniature surgical robots.
Traditional scopes, and even those associated with the da
Vinci system, require their own incisions. Dr. Oleynikov
envisioned robots that would be able to enter and exit the
body through incisions made for other instruments – thus
reducing the number of cuts and shortening healing time.
He envisioned tiny robots
the size of a lipstick
case that could be placed
in a patient’s abdominal
cavity and move around in
a patient’s body.
16
fall 2007
Drs. Oleynikov and Farritor decided to pursue miniature
robots as their research proposal during an idea-filled lunch
two months later at a Cajun restaurant in Lincoln, complete
with napkin drawings of potential robot models.
Marsha Morien, executive director of the University of
Nebraska Center for Advanced Surgical Technology,
remembers the lunch as an energetic encounter with ideas
flowing quickly between the two scientists.
UNMC
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17
The ceiling pan/ tilt robot sits inside
a simulated thorax. This camera robot
magnetically affixes to the surface of
the abdomen to provide the surgeon
with a view of the surgical site.
The partnership between Drs. Oleynikov and Farritor is
an example of a common theme being emphasized at
research institutions around the world – collaboration
across disciplines.
With an increased push toward clinical and translational
research, scientists around the world are being asked to
look beyond their own fields for collaborative partners.
“It really is an equal partnership with each one of us adding
vital components to the mix,” Dr. Oleynikov said. “Without
one, the other would not succeed.”
Dr. Farritor agreed, noting that the timing seemed right.
“It works well because he’s a medical guy who knows a
little about robots, and I’m a robot guy who now knows a bit
about medicine,” Dr. Farritor said.
The collaboration between Drs. Oleynikov and Farritor is a
perfect example of such cooperation, said Tom Rosenquist,
Ph.D., vice chancellor for research at UNMC.
“Drs. Oleynikov and Farritor have combined their
considerable expertise and produced robots that could
“Robots are the future
of surgery, I truly
believe that. I envision
a time when a surgeon’s
hands no longer need
enter a patient’s body.”
Dmitry Oleynikov, M.D.
Department of Defense – which has authorized the team to
receive grants of about $6 million to advance development
of the robots.
If a soldier is wounded on the battlefield, theoretically a
medic at the site could insert a robot into a patient, allowing
a remote surgeon to quickly diagnose a wound – potentially
speeding treatment and reducing casualties.
NASA also has expressed interest in the robots under
the premise that they could be used should a medical
emergency occur in space.
The robots have proven successful in animal trials –
assisting surgeons in the removal of a pig’s gall bladder with
no harm to the animal.
18
fall 2007
“The robots performed very well and provided the kind of
support we had envisioned they would,” Dr. Oleynikov said.
The team is now awaiting approval from UNMC’s Institutional
Review Board to begin human trials. If human trials prove
successful, Dr. Oleynikov said it’s possible the surgical robots
could be on the market as early as next year.
To market the robots and other technology developed
along the way, Drs. Oleynikov and Farritor have founded
Nebraska Surgical Solutions – a start-up company that
will let them capitalize on what could be a revolutionary
development in the world of surgery.
“Robots are the future of surgery, I truly believe that,” Dr.
Oleynikov said. “I envision a time when a surgeon’s hands
no longer need enter a patient’s body.”
lead to a surgical revolution,” Dr. Rosenquist said. “They
demonstrate how such collaboration can lead to scenarios
where everyone wins.”
Their cross disciplinary approach and venture into surgical
robots also drew praise from one of the world’s leading
surgeons, Richard Satava, M.D., professor in the University
of Washington Department of Surgery and founder of the
international conference, Medicine Meets Virtual Reality.
“Such a revolutionary concept requires just the type of
multidisciplinary team with tremendous experience in
innovation that has been assembled,” Dr. Satava said.
“This not only brings credibility to the project, but also
greatly increases the chance of success.”
To both men, their work represents a perfect and simple
amalgamation of the expertise they bring to the table.
Nebraska is NOTEworthy
The vision of Dmitry Oleynikov, M.D., of a world where
robots replace surgeons’ hands within a patient’s body may
already be catching up with reality.
A new push in the world of surgery is the development of
what is called Natural Orifice Transluminal Endoscopic
Surgery or NOTES.
The idea behind NOTES is for surgeons to enter the body
through natural orifices such as the mouth, eliminating
external incisions and visible scars for patients.
Dr. Oleynikov and Shane Farritor, Ph.D., have developed
a special robot that enters a person’s mouth, moves down
the esophagus and into the stomach, where it makes a
small incision to gain access to the inner body and assist
with surgery. The robot then exits the body the same way it
entered and the surgeon laproscopically stitches the robot’s
incision, leaving no visible scars.
The team has begun testing their NOTES robot on animals.
“Time will show that using our robots is the best way to do
NOTES,” Dr. Farritor said.
This is so, Dr. Oleynikov said, because the current method
of performing NOTES involves using tools not suited for the
job, particularly a camera scope that is actually designed to
remove polyps on the colon, not perform surgery.
“Surgeons who use our NOTES robots will have the right
tool for the job,” Dr. Oleynikov said.
UNMC
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19
Although some of the findings were published in the
journal “Biochemistry” between 2004 and 2007, there is
more to the story.
Proteins and tigers
and hormones!
Oh, my!
The technology ultimately caught the attention of
UNeMed, the technology transfer organization for UNMC.
The technology was so compelling that it was identified
as having commercial potential. It is now being further
developed, with several patents pending.
The possibilities for Dr. Bedows’ new technique are vast in
the recombinant protein purification world, a $36 billiona-year industry. It lowers the cost and cuts the time for
purification from days to hours.
Part of the cost savings come from eliminating the need for
disposal since no toxic chemicals are used.
by Vicky Cerino
While studying early pregnancy loss, a UNMC
scientist discovers a better way to purify proteins
To researchers, scientific discoveries are like dangling fresh
meat in front of tigers. They are impossible to ignore.
Such was the case for Elliott Bedows, Ph.D., and Jason
Wilken, Ph.D., whose discovery significantly changed the
course of a research project and may ultimately benefit
humans and endangered tigers. It also may impact a $36
billion-a-year industry.
The project: Advance reproductive biology in humans.
The problem: Discover the cause of pregnancy loss within
the first three weeks of conception.
The approach: Compare the structure-function
relationships of human chorionic gonadotropin (hCG), a
hormone made in response to human pregnancy, to mCG,
the parallel hormone of the Macaque monkey.
Conventional wisdom said the two hormones had identical
physiological functions.
But, Drs. Bedows and Wilken, a graduate student at the
time and now a postdoctoral fellow at Yale University
School of Medicine, found a difference that challenged
scientific literature.
To prove their findings, they ran their arduous experiments
again and again.
20
fall 2007
In November 2006, Allied Minds, a Boston-area company
that invests in successful early stage technology, purchased
the license, formed Purtein, LLC, and invested $500,000.
James Linder, M.D., president of UNeMed, said the
“We wanted to find the difference, so we built new, but
related proteins to study,” said Dr. Bedows, associate
professor, UNMC School of Allied Health Professions.
“It’s a unique concept because most purification schemes
work on charge or on an amino acid sequence, or some
other basic chemical aspect. Our technique targets the
shape of a molecule, which is why it’s such a novel
approach,” Dr. Bedows said.
“When you introduce a
foreign matter, it might
work the first time, but
after that, the immune
system may destroy it.
Sterilization is one concern,”
Dr. Armstrong said.
The team is testing small amounts of tiger hormones on
cell cultures in the laboratory and preliminary results show
the technology works.
By safer, Dr. Bedows was referring to the toxic chemicals
that are often used in basic cell biology research. Using
these chemicals drives up the cost of the research and
ultimately the cost of drug development.
The technique did more than purify the targeted protein;
it purified every protein they tested with the same
general shape.
In 2005, Dr. Bedows used the technology to engineer and
purify new tiger hormones to stimulate ovulation for in vitro
fertilization in order to reproduce endangered tigers. The
purified hormones appear to be far superior to hormones
currently used from humans, cattle or pigs. Hormones from
humans, cattle and pigs
can produce an unwanted
immune system response
in tigers.
“We are building new tiger hormones and purifying them
in high enough quantities so the zoo can start using tiger
hormones for in vitro fertilization and assisted reproduction,”
Dr. Bedows said. “What they get is a tiger hormone that is so
genetically similar that the tiger recognizes the hormone as
its own, thereby avoiding potential side effects.”
“We had to figure out how to purify all of these proteins –
called recombinant proteins. We developed a technique that’s
much faster, cheaper and safer than anything that existed.”
Recombinant proteins are natural proteins engineered
in a different cell system to replicate large quantities of
proteins for use in commercial industry, drug development,
research, and in diagnostic applications. But before
recombinant proteins are useful, they must be purified.
Even before licensing the technology, Dr. Bedows was
using it to help the Henry Doorly Zoo in Omaha. He, Doug
Armstrong, D.V.M., associate director for medicine research,
and Naida Loskutoff, Ph.D., reproductive physiologist, at
the Henry Doorly Zoo, have been collaborating since 1994
on the zoo’s assisted reproduction program to manage the
genetic diversity in zoo animals.
Dr. Bedows draws blood from a female tiger at the zoo with the
help of keeper Hannah Savorelli.
venture with Allied Minds is an exciting one. “We see the
partnership as a fast, effective way to commercialize this
novel technology.”
“That’s the beauty of the invention,” said Chris Silva, CEO of
Allied Minds and Purtein. “They created a way of purifying
proteins in a novel and economical manner that brings
down the cost.”
“The next step is to produce enough hormones to try it in a
tiger,” Dr. Armstrong said. “If it works, we’ll gear up a whole
system to produce enough hormones for our zoo, and also
share them with others. There are only a couple of places
in Europe that have attempted assisted reproduction with
tigers. We’ve heard of no one else who has invested effort
and resources to produce big cat hormones.”
After 30 years in the laboratory, Dr. Bedows was reminded
that surprises in basic research are impossible to ignore.
“It turns out, much to my chagrin, that the technology to
advance our research was more valuable than the research
itself – we got more funding for the technique than for the
scientific data we produced,” Dr. Bedows said.
Dr. Bedows explains his research in a video at www.unmc.edu/discover
UNMC
discover
21
Omaha’s “CSI”
unlocks
hidden clues
by Tom O’Connor
Within the darkened lab, Mellissa Helligso
waves the crime scene scope over size 6
floral panties that have been laid flat on
the table.
She’s looking for semen on yet another sexual assault case. More than 700
similar cases were reported in Omaha last year.
Helligso, an analyst with UNMC’s Human DNA Identification Laboratory, knows
body fluids glow under the UV light. All except blood.
“The evidence doesn’t lie,” Helligso says, turning to look at the mug shots of
24 murderers and rapists who are now behind bars, thanks to evidence found
in that very lab.
“DNA is foolproof,” she said.
Hours earlier, Helligso logged the evidence, wondering if this case will be one
of the few that actually goes to trial. Nonetheless, she assigns a three-digit
number to track the clothing as it makes its way through the laboratory, which
is part of UNMC’s Molecular Diagnostics Laboratory.
Omaha’s version of the popular TV show, “CSI,” plays out daily here as police
detectives bring manila envelopes, sealed with red evidence tape, into the
laboratory. Helligso empties the contents onto a freshly bleached laboratory
bench. Then, wearing a white lab coat and sterile gloves, she grabs the crime
scene scope.
Nearby, colleagues do tissue typing for transplant patients, as well as clinical
tests on HIV, tumors, viruses and for paternity.
22
fall 2007
UNMC
discover
23
Focused on the clothing, Helligso swabs the area to extract the DNA and runs it
through a battery of tests that result in a unique profile, which may, or may not,
connect the suspect to the crime.
Deoxyribonucleic acid, or DNA, is the genetic code of all humans. Found in
every cell throughout the body, it determines such human traits as eye and
hair color, stature and bone density. No two people – with the exception of
identical twins – have the same DNA blueprint.
Left at a crime scene, that distinct signature has sent suspects to prison; it also
has provided those wrongly accused with a “get out of jail free” card.
Within a week, Helligso will complete testing on all the evidence, as well as
prepare a report of the forensic findings for police.
The UNMC laboratory – one of two academic health science centers in the
country to house a forensics lab – also is one of two DNA labs in Nebraska. The
other is at the Nebraska State Patrol offices in Lincoln.
DNA found at crime scene is matched to a
sample from a suspect. No two people – with
the exception of identical twins – have the
same DNA blueprint.
DNA profiles are so unique
that odds are greater than
1 in 1 quadrillion that a DNA
sample from one person
would match another’s.
1in
1,000,000,000,000,000
UNMC established the DNA laboratory with its hospital partner, The Nebraska
Medical Center, in 1996 in response to the needs of the Douglas County
Attorney’s Office.
At the time, DNA forensic analysis was done at a limited number of places
around the country. When necessary to make its case, the Douglas County
DNA analyst Kaye Shepard, left, logs in evidence
brought by Omaha Police Detective Robert Butler
and Sergeant Staci Witkowski.
Joe Choquette reviews raw DNA data
on the genetic analyzer. The analyzer
measures the peaks, which are
compared against other DNA samples.
Attorney’s Office would send DNA evidence to a lab in California, go
there to take depositions, then fly the DNA experts to Omaha to testify
at the trial.
the American Society of Crime Laboratory Directors. Dr. Wisecarver
estimates that probably 70 percent of the lab’s work today is now
involved in forensic testing.
“This was very expensive,” said Jim Wisecarver, M.D., Ph.D., professor
of pathology and microbiology and director of the Human DNA
Identification Laboratory. “We were approached by Jim Jansen (then
Douglas County Attorney) and Don Kleine (then chief deputy) about
creating our own DNA forensic testing lab at UNMC. It would save
Douglas County lots of money, and it would provide attorneys with
much easier access to DNA experts.”
While it’s an impressive workload, the lab also performs hundreds of
tests for patients at The Nebraska Medical Center.
Kleine, who is now the Douglas County Attorney, said his office relies
on UNMC for help in most of its high-profile murder cases. “The DNA
laboratory at UNMC gives us a facility that is recognized by people in
the community as the gold standard,” he said.
“People view UNMC as a leader in the medical arena. They use
the same DNA testing process for people undergoing bone marrow
transplants. It lends complete credibility to our DNA evidence. It’s
tremendous to have this kind of expertise at the local level.”
In addition to its credible reputation, Kleine said UNMC’s DNA lab
brings neutrality – just as important in a court of law. “The fact that
UNMC is a non-law enforcement agency is critical. They will test DNA
for anybody,” he said.
“We’re just there to report the facts,” Dr. Wisecarver said.
The DNA lab has processed evidence for nearly 800 cases in the
past 11 years. In 2000, the lab received forensic accreditation from
24
fall 2007
“Our main focus is still patient care – that’s the mission of the
university,” he said. “Our goal with the DNA testing is simply to help
out the various law enforcement agencies that come to us.”
As its workload has increased, the DNA lab has grown to include two
full-time analysts – Joe Choquette and Lloyd Halsell – and two parttimers, Helligso and Kaye Shepard.
The lab more than pays for itself, Dr. Wisecarver said, noting the $500
charge for each DNA specimen that is tested. “Unlike health care,
where you are working on discounts, forensics pays dollar for dollar.
This helps our patients and the citizens of Nebraska.”
The Nebraska State Patrol in Lincoln, meanwhile, offers free testing,
which has resulted in a nine-month backlog of cases, Helligso said,
noting, “police appreciate that we can give them results quickly.”
Although “CSI” has given forensic medicine a glamorous image, the
majority of cases are more routine and involve requests from the public.
“We do receive some odd requests,” Dr. Wisecarver said. “Once we were
contacted by an individual who suspected that someone had urinated
in his coffee cup, and he wanted us to test for it.”
UNMC
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25
Unmistakable evidence
Proving a murder case without a dead body is no small feat.
That was the task the Douglas County Attorney’s Office faced
earlier this year when a 19-year-old Omaha woman, Jessica
O’Grady, went missing May 10, 2006.
Police investigators on the case focused their attention on
O’Grady’s boyfriend, Christopher Edwards, as the leading suspect.
In the course of the investigation, the police searched Edwards’
bedroom and car and found excessive amounts of DNA evidence.
O’Grady’s blood was found on a sword recovered from Edwards’
residence as well as on a headboard, mattress and the ceiling of
Edwards’ bedroom.
The DNA evidence was taken to the UNMC Human DNA
Identification Laboratory for processing. “Because they didn’t have
a body, the county attorney’s office wanted all the DNA evidence it
could possibly find,” said Jim Wisecarver, M.D., Ph.D., lab director.
“They wanted to build an ironclad case.”
It only takes a small quantity of DNA – between 15 and 20 cells
– to establish a profile. “We can make a profile from saliva left on a
cigarette butt, a licked envelope or postage stamp, or skin cells left on
a firearms cartridge, beverage can or bottle,” he said.
English scientist Alec Jeffreys first proposed DNA analysis in 1985. By
the late 1980s, it was being performed by law enforcement agencies,
including the Federal Bureau of Investigation and by commercial
“We can make a profile from saliva
left on a cigarette butt, a licked
envelope or postage stamp, or skin
cells left on a firearms cartridge,
beverage can or bottle,”
Jim Wisecarver, M.D., Ph.D.
“You can’t create DNA. You’re not going to get false results. That’s
why it’s so powerful.”
In his closing argument at the trial, Kleine held up a sign with a large
number containing 18 zeroes. He wanted to make the point that there
is no disputing DNA evidence. “There was no question (the blood
belonged to O’Grady). The probability that it could have been someone
else’s blood was like 1 in a quintillion – 10 to the 18th power.
“The other side will always try to attack the credibility of DNA
evidence, but UNMC’s lab stands with any in the country. It has
the credentials, background and expertise,” Kleine said. “I’ve
talked to juries afterwards. They always say they found the DNA
evidence to be very credible…they have no issue with it. That
speaks volumes.”
26
fall 2007
Each day, the world’s littlest human beings fight for their lives in Neonatal
Intensive Care Units, their lungs unable to breathe on their own, their
bodies unable to regulate their temperature, their blood pressure
fluctuating to life-threatening levels.
Sometimes born at less than 2 pounds, these babies require around-theclock attention to survive.
A pediatrician with three decades of experience in neonatology and
developmental medicine, Howard Needelman, M.D., knows firsthand the
obstacles that premature infants may face, both during those initial months
of hospitalization and throughout their lifetime.
Through the follow-up program, Developmental TIPS (Tracking Infants
Progress Statewide), approximately 5,000 children have been assessed for
neurodevelopmental disability. The children are assessed through various
tools, depending on factors including the extent of their prematurity,
complexity of their medical history, and the results of preliminary hearing
and vision screenings. The children are followed through age 3.
Douglas County Attorney Don Kleine built his case on the DNA
evidence, and during the two-week trial, both Dr. Wisecarver and
analyst Mellissa Helligso were asked to testify. The DNA evidence
was compelling, and Edwards was found guilty of the murder in
March, 2007. It was the first time in Nebraska history that a jury
had rendered a guilty verdict in a murder trial in which the body
had not been found.
“Trying someone for murder without a body is a unique situation,”
Kleine said. “It doesn’t happen very often. I relied on the DNA
evidence. Jim and Mellissa did a great job of explaining what DNA
is and the scientific process involved in analyzing DNA.
Tracking tiny patients
For the past 13 years, a program led by Dr. Needelman and Barbara
Jackson, Ph.D., director of Education and Child Development at UNMC’s
Munroe-Meyer Institute, has served children who spend at least 48 hours
in one of Nebraska’s seven major NICUs.
The evidence was unmistakable – all the blood samples belonged
to O’Grady, who was a student at the University of Nebraska at
Omaha. Edwards’ mattress had been turned over when investigators
reached the scene. It was covered with a huge pool of dried blood.
The bedroom walls had been freshly cleaned, but investigators were
still able to retrieve blood samples from the walls.
under the
microscope
“Developmental TIPS is the largest standardized follow-up program of
its kind in the country,” Dr. Needelman said. “It ensures that each child
by Bill O’Neill
is assessed by a team with expertise in early childhood development,
which in turn provides the children with the best opportunity for success,
especially if early intervention is necessary.”
That early intervention usually comes from a school district or educational
service unit, and often involves physical, occupational or speech therapy.
The intervention also highlights the collaborative nature of the TIPS program.
“One key to the TIPS program’s success was the collaboration across
entities to establish a standard system of follow-up and one centralized
database,” said Dr. Needelman, an assistant professor of pediatrics at
UNMC. “The university, the hospitals, the schools, the educational service
units, the state of Nebraska – a lot of entities have worked together to
ensure this program’s success.”
The program’s findings, Dr. Needelman said, are mixed. Although the
smallest babies have the highest risk of disabling conditions such as
cerebral palsy, mental retardation, lung problems, blindness and others,
many of those babies do quite well. The larger babies – traditionally
thought to be low-risk because of the relatively few services required in the
NICU – also do well, but they ultimately receive early intervention services
at a rate five to 10 times greater than the average population.
“As a neonatologist, it’s wonderful to know that most kids who come out
of the NICU do pretty well, even the most vulnerable, smallest children,”
Dr. Needelman said. “That said, I think our research results have shown
that all children who are in the NICU – even the babies who are there
for a short time – need to be followed closely so that they can be given
appropriate attention medically and educationally, to ensure that they
reach their full potential.”
Funded primarily by the state
Department of Education with
assistance from the state’s hospitals
and the Department of Health and
Human Services, Developmental
TIPS does not charge families for
services. A pilot program, measuring
how NICU graduates function
through their kindergarten years, is
being considered.
Members of UNMC’s Human DNA Identification Laboratory
team are, from left, Mellissa Helligso, Lloyd Halsell, Dr. Jim
Wisecarver, Joe Choquette and Kaye Shepard.
laboratories. It consists of comparing selected segments of DNA
molecules from different individuals. Because a DNA molecule
is made up of billions of segments, only a small portion of an
individual’s entire genetic code is analyzed.
“Over the years, DNA testing has become much more sophisticated,”
Dr. Wisecarver said. “Today, it’s all done via computer. We look for
the number of repeating units on the chromosome, and we test 16
different spots (or loci) on the DNA. When you get a match, it’s pretty
much a lock.”
With many patients, the goal
is to get them to function as
19-month old Kylie Gilbert looks for Clifford
the Big Red Dog during a Developmental TIPS
assessment session that includes her mom, Vicki,
Barbara Jackson, Ph.D., and Howard Needelman,
M.D. Kylie is one of triplets.
UNMC
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Construction
on the twin to
the Durham Research Center is expected to
be completed in early 2009. The 10-level facility
will contain 252,179 gross square feet with 98
state-of-the-art laboratories, as well as office
space for investigators and laboratory support
space. Most of the laboratories will be dedicated
to research in the College of Medicine, the Eppley
Cancer Center, the College of Pharmacy, and
to support operations of the Nebraska Public
Health Laboratory and the University of Nebraska
Center for Biosecurity. Funding for the $74 million
facility comes largely through private support,
with legendary Omaha businessman Chuck
Durham, president and CEO of Durham Resources,
providing the lead gift.
discover
UNMC
University of Nebraska Medical Center
985230 Nebraska Medical Center
Omaha, Nebraska 68198-5230
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