Summer 2015 Journal

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UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES • SUMMER 2015

expanding knowledge

RESEARCH: For a Better State of Health

Message from the Chancellor Dear Readers, UAMS, like other universities, is primarily in the knowledge business. As an academic health sciences center we also provide comprehensive health care services, but our heart and soul is as a health sciences university.

We develop new knowledge through research, transmit knowledge through education programs and use our knowledge for the benefit of individuals and society at large. It is all about knowledge, expanding our understanding of the known world and the human condition and using that expanded knowledge for the benefit of everyone in society.

This issue of the UAMS Journal is about research. We have previously shared stories about a number of research programs at UAMS in many areas: cancer, aging, mental health and others.

This issue continues to focus on what makes us unique as an academic medical center and health sciences university.

The foundation of our uniqueness is research. We develop new knowledge and use that knowledge to educate and train the next generation of health professionals across 74 different professional degree programs in five colleges and the graduate school. We also use that knowledge to provide innovative care of a type that is not routinely available elsewhere. We don’t try to separate the components of our mission. We consciously endeavor to integrate them for a value that is greater than the sum of its parts.

I believe that knowledge is the foundation of everything good. Nothing gets better without new information and better understanding. This is true in science and it is true in society. We hope you enjoy reading about and learning more about UAMS as we endeavor to learn more about you.

Together we can change the future, and that is what great universities do.

Dan Rahn, M.D. Chancellor, University of Arkansas for Medical Sciences

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UNIVERSITY OF ARK ANSAS FOR MEDICAL SCIENCES

Journal SUMMER 2015

Editor

Elizabeth Caldwell Creative Director

Laurie Shell Writers

Ben Boulden Katrina Dupins Jon Parham David Robinson Susan Van Dusen Spencer Watson Photographer

Johnpaul Jones

CONTENTS Overview....................................................................................................................... 4 Empowering Research Translational Research Institute.......................................................................................... 6 Centers for Biomedical Research Excellence........................................................................ 9 New Faces of Research...................................................................................................... 12

Community Northwest Arkansas Marshallese....................................................................................... 14 Tackling the Economics of Health.................................................................................... 16 VA Mental Health............................................................................................................. 18 Nursing PCORI................................................................................................................ 20

Educating New Researchers INBRE.............................................................................................................................. 23 Student Diversity............................................................................................................... 26 Interdisciplinary Biomedical Science................................................................................. 28

Economic Return illustrations

April Lovell Leslie Norris

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Chancellor

Dan Rahn, M.D. Vice Chancellor for Communications & Marketing

Leslie Taylor

The UAMS Journal is published twice a year by the Office of Communications & Marketing, University of Arkansas for Medical Sciences, 4301 W. Markham St. #890, Little Rock, AR 72205.

Arkansas Research Alliance............................................................................................... 31 BioVentures........................................................................................................................ 34 Little Rock Technology Park............................................................................................. 38

Ongoing Research Surgeon Researchers.......................................................................................................... 40 Arkansas Children’s Nutrition Center............................................................................... 42 Child Injury Prevention..................................................................................................... 44 Cancer Vaccine.................................................................................................................. 46 Osteoporosis...................................................................................................................... 48 Radiation Injury................................................................................................................ 50 Food Allergies.................................................................................................................... 52 Meth Addiction................................................................................................................. 55 Lung Cancer...................................................................................................................... 58 Biomedical Informatics..................................................................................................... 59

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Phone: (501) 686-5686 Fax: (501) 686-6020 -----------------------

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OVE R VIE W

RESEARCH MATTERS

“

Our faculty who do research are on the cutting edge of their fields.”

Medical Breakthroughs Start in the Lab

By Elizabeth Caldwell

W

ithout medical

research, there would be no antibiotics to treat pneumonia, children with polio would still be breathing in iron lungs, and bloodletting with leeches would still be used to treat everything from inflammation to stroke.

And without scientists whose overwhelming desire and interest is in discovering why the world works as it does and how they can improve the health and well-being of populations large and small, there would be no medical research.

At UAMS, the state’s only academic medical center, the research laboratory is central to its mission. UAMS scientists are deeply committed to a wide range of research — from basic science that produces new knowledge that can lead to breakthroughs in medical treatment, to translational research that speeds treatments to patients, to clinical trials that confirm new therapies.

To recognize the importance of research at an institutional

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level, in 2013, Chancellor Dan Rahn, M.D., converted the position of vice chancellor for research from part time to a fulltime position with responsibility to work with all colleges to advance strategic initiatives in research.

Vice Chancellor Lawrence Cornett, Ph.D., whose lengthy career once included laboratory research, was appointed to the position and now focuses all his attention on advancing UAMS research and especially team science.

“We are having an impact in multiple areas,” Cornett said.

“To be a complete academic medical center, it is important to have research across the translational spectrum —basic, clinical, and implementation science.”

One of the most important aspects of academic medical centers compared to other health centers is the ability to have clinical trials available to patients.

“Our faculty who do research are on the cutting edge of their

fields. They read the latest literature and perform work in their particular area, so they are extremely knowledgeable about the best treatments for a given disease,” Cornett said. “For people with life-threatening diseases, this can be their best chance.”

He said studies show the public is supportive of research, but doesn’t necessarily understand how expensive it is or that the costs are borne partially by the federal government, partially by industry and partially by universities themselves.

Research funding across UAMS faculty for the fiscal year ending June 30, 2015, is $108.72 million. This includes scientists at Arkansas Children’s Hospital and the Central Arkansas Veterans Healthcare System who are also UAMS faculty.

This is a critical time because of limited research dollars available amid federal cutbacks, Cornett said. Federal support for biomedical research has

UNIVERSITY OF ARK ANSAS FOR MEDICAL SCIENCES

Lawrence Cornett, Ph.D., vice chancellor for research, focuses on advancing UAMS research and team science.

been relatively flat over the last 10-15 years and hasn’t kept up with inflation. At the same time, industry has stopped supporting early-stage research because the return is so far down the road. It supports more applied research on drugs, devices and diagnostics believed to be marketable and successful in clinical trials.

That’s another thing that

makes academic medical centers different from other health centers — scientists don’t simply perform industry-sponsored research.

“We do investigator-initiated research. Our faculty are coming up with the ideas for research projects,” Cornett said.

For instance, the 1920 discovery of insulin to treat

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diabetes was made by university scientists. Prior to the discovery of insulin, diabetes was a death sentence. Those with childhood onset diabetes wouldn’t live much past their teens. Today, with treatment, these patients live full and active lives — a testament to the power of medical research.

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E M P O W E R ING R ESEA R C H

TRANSLATIONAL RESEARCH INSTITUTE

Beyond the Lab

By David Robinson

U

AMS’ Vladimir Zharov, Ph.D., is a “translational” researcher. His internationally recognized nanomedicine research has led to new, exciting possibilities for early diagnosis of cancer, infections and stroke, as well as prospects for commercialization of in vivo noninvasive blood testing.

The National Institutes of Health (NIH) is looking for more Zharovs in the biomedical research field, and UAMS, through its NIH-funded Translational Research Institute, is working to oblige.

UAMS has more than 500,000 square feet dedicated to understanding life at organ, cell and gene levels. This important “basic science” has long been the foundation of biomedical innovation and discovery. Even so, attention has turned in the last decade to expediting the translation of laboratory discoveries to improved diagnosis and treatment of patients.

Citing NIH statistics, Laura James, M.D., director of the UAMS Translational Research Institute, noted that new drugs, devices and other interventions take an average of 14 years to bring to market, cost as much as $2 billion, and experience a 95 percent failure rate.

“The process can be extremely onerous, because researchers must contend with numerous regulatory hurdles, design feasible yet rigorous clinical studies, find people who are willing and eligible to participate in the research, and compete for a shrinking supply of taxpayer dollars dedicated to research,” James said.

In 2006, the NIH offered competitive awards to research institutions with the best ideas for overcoming the time and cost barriers and improving the success rate of translational research.

The effort is funded through the National Center for Advancing Translational  6

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Sciences (NCATS) Clinical and Translational Science Awards (CTSA).

UAMS received a CTSA in 2009. The $19.9 million award, along with significant institutional funds, supports the UAMS Translational Research Institute, which was established in 2011.

The translational research at a CTSA goes beyond extending basic science discoveries into clinical settings; it also requires critical involvement of community members and clinicians at every stage of research, from the researcher’s idea to the implementation of results into the community. It also includes studying how research findings are being implemented to determine the best methods that will produce sustained changes in the practice of medicine and in human health.

The Translational Research Institute uses a number of approaches to make translational research more efficient and improve researcher success. These include better use of technology and available patient data such as the electronic health record; promoting collaboration and team science among researchers; partnering with communities; commercialization of new products, services and treatment approaches; and streamlining regulatory and other research processes.

Targeted funding from the institute can also help speed the pace of research. A pilot grant helped Zharov move closer to commercialization by supporting development of a clinical prototype of a circulating tumor cell detection device.

“The purpose of our efforts is to improve the health and health care of Arkansans, so we are supporting research that impacts Arkansas,” James said. “This is vitally important given our state’s health status ranking of 49th nationally with high rates of obesity, diabetes and cancer, along with underlying lifestyles that contribute to these conditions.”

The institute’s mission includes establishing enduring partnerships with communities across the state, especially rural and medically underserved communities. This community 8

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“

The purpose of our efforts is to improve the health and health care of Arkansans.”

engagement work is helping ensure that research is relevant to Arkansans.

Community engagement, along with a pilot grant from the institute, helped researchers at the UAMS campus in northwest Arkansas obtain two national grants totaling $5.1 million to study diabetes and other chronic diseases in the underserved Marshallese, Hispanic and Hmong communities.

The future of translational research depends on the support and development of talented new researchers, said Mary Aitken, M.D., M.P.H., who co-leads the institute’s KL2 Mentored Career Development Program with Pedro Delgado, M.D. A cornerstone of the institute, the KL2 program helps new researchers gain competence in research approaches and work in teams to maximize success.

Since 2009, 16 junior faculty have been named KL2 scholars, with many establishing funded, independent research programs.

“The KL2 gave me the opportunity to redirect my medical career toward research while I was completing a clinical fellowship in asthma and immunology at the University of Virginia,” said Hot Springs native Joshua Kennedy, M.D., who received a KL2 award in 2013. “The award provided the means to pursue research in my home state with a team that is helping advance asthma research on a national scale.”

Two former scholars, Dennis Kuo, M.D., and Holly Felix, Ph.D., have competed successfully for federal grants and presented their findings at the National Press Club in Washington, D.C., in conjunction with their published work in the prestigious health policy journal Health Affairs.

“One of our goals is to help train the next generation of translational researchers,” Aitken said. “Our graduates are providing a great return on investment.”

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Edgar Garcia-Rill, Ph.D., leads the Center for Translational Neuroscience.

CENTERS for BIOMEDICAL RESEARCH EXCELLENCE

Federally Funded Centers Deliver Results

By David Robinson

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wo multi-million dollar

research programs at UAMS supported by federal grants are having a real-world impact on health problems facing Arkansans today.

The Center for Biomedical Research Excellence (COBRE) program of the National Institutes of Health (NIH) has allowed UAMS to help Arkansas dramatically improve its infant mortality rate. It is also helping UAMS scientists tackle an array of diseases caused by pathogenic microbes.

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UAMS competed for and won grants for two COBRE programs. The first, led by Edgar Garcia-Rill, Ph.D., has received three grants since 2004 totaling $22.5 million and is in its third and final phase.

The second program, awarded in 2012 and led

by Mark Smeltzer, Ph.D., was established with $10 million. Both COBREs have enabled critical upgrades of sophisticated equipment that elevates biomedical research capabilities for UAMS researchers. ďƒł www.uamshealth

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“ Arkansas is among 26 states and Puerto Rico that are eligible to compete for COBRE grants, which are designed to help strengthen research programs in states with historically low rates of NIH funding. COBREs are funded by the Institutional Development Award (IDeA) program at the NIH National Institute of General Medical Sciences.

COBREs nurture new researchers with mentoring and funding support to help establish their research programs. Individual COBREs also have their own scientific themes.

Center for Translational Neuroscience With a track record of 12 years, Garcia-Rill can highlight many achievements from the COBREfunded Center for Translational Neuroscience (CTN) he directs. One significant result is in the area of infant mortality.

In 2006, 8.5 of 1,000 newborns died in Arkansas. Since then, the rate has fallen to 6.8 per 1,000, with the biggest improvement among African-Americans.

With more than 37,000 babies born in Arkansas each year, that equates to saving about 60 babies a year, said Garcia-Rill, a professor in the UAMS College of Medicine.

The decline in mortality correlates with the start of his COBRE-supported telemedicine program, Pediatric Physician Learning and Collaborative Education (Peds PLACE), which connects UAMS neonatologists with physicians caring for newborns in hospital nurseries across the state.

Also, in the first 10 years, the CTN’s researchers generated $32 million in additional grants for UAMS as a result of their findings and published more than 400 articles, “a huge 10

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We’re building a foundation to make meaningful discoveries.”

output,” he said. Garcia-Rill also authored the book, Translational Neuroscience: A Guide to a Successful Program, in 2012.

The CTN is one of the few COBREs in the country conducting human-participant translational research. Examples include studies of transcranial magnetic stimulation, which has been shown to relieve symptoms of tinnitus (ringing in the ears); discoveries related to sleep and weight gain; and new discoveries, recently accepted for publication, of mechanisms behind schizophrenia and insomnia.

“I think it will lead to new treatments for schizophrenia,” Garcia-Rill said.

Center for Microbial Pathogenesis and Host Inflammatory Responses Smeltzer, who directs the COBRE-funded Center for Microbial Pathogenesis and Host Inflammatory Responses, said the name reflects the fact that his team is taking a comprehensive approach to understanding the interactions between microbial pathogens and their human hosts.

“We believe that a better understanding of these complex interactions will lead to the development of novel, more effective therapies,” said Smeltzer, professor in the Department of Microbiology and Immunology.

As an example, two center researchers are studying two viruses and their interaction with host cells, and the results may ultimately prove useful as a novel means of combating cancer.

The work of the COBRE is made even more significant and urgent given the alarming rise of antibiotic resistance.

“This has made infectious disease a greater threat now than it has been in the last half century or longer,” Smeltzer said.

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Mark Smeltzer, Ph.D., directs the Center for Microbial Pathogenesis and Host Inflammatory Responses.

Consider, for example, methicillin-resistant Staphylococcus aureus (MRSA) sometimes referred to as a super bug. The number of MRSA deaths each year in the United States is comparable to, if not greater than, the number of deaths caused by five of the top 10 cancers.

The COBRE is stocked with high-achieving new researchers based in the College of Medicine Department of Microbiology and Immunology, whose department chair, Richard Morrison, Ph.D., co-directs the COBRE. In fact, it is the quality of their research that was key to landing the prestigious grant.

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The COBRE primarily supports four new faculty researchers – called project leaders – through mentorship and research funding.

They are off to a great start. One project leader, Craig Forrest, Ph.D., quickly earned a perfect score on a separate NIH grant application and is now independently funded. A replacement for Forrest has been recruited and will become a project leader later this year, Smeltzer said.

“We’re building a foundation that will maximize the ability of our investigators to make meaningful discoveries,” Smeltzer said.

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“

When you get ideas and work well together, things just kind of take off.”

NEW FACES OF RESEARCH

Microbiology, Immunology Researchers Collaborate

By David Robinson

O

ne is studying dangerous bacteria, another how to prevent the herpes virus from causing cancer.

The seven junior faculty in the UAMS College of Medicine’s Department of Microbiology and Immunology are making their mark in the quest to improve human health through basic research.

And they are attracting the type of national funding that makes it all possible.

Department Chair Richard Morrison, Ph.D., said the group of rising research stars he’s recruited to UAMS since 2009 has brought an infusion of energy and cooperation. It started with his plan to hire young researchers and establish a mentoring program. He has been patient, seeking the best talent while taking pains to ensure they would contribute to a collegial, collaborative environment.

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The payoff is seven new junior faculty who have since acquired nine grants totaling nearly $8 million. Morrison’s hires include Craig Forrest, Ph.D.; Jason Stumhofer, Ph.D.; Jon Blevins, Ph.D.; Karl W. Boehme, Ph.D.; Jia Liu, Ph.D.; Dan Voth, Ph.D.; and Lin-Xi Li, Ph.D. They are quickly falling off the “junior” list. Voth became a tenured associate professor last year, and Blevins and Forrest are on course to achieve tenure this year.

Forrest and Stumhofer were crucial to helping UAMS secure a $10 million NIH Center of Biomedical Research Excellence (COBRE) award in 2012. Forrest earned a perfect score for his project submitted with the COBRE application and Stumhofer scored near the top, ensuring the application’s success.

The COBRE is a major bonus, directly benefitting the department’s newer researchers.

It provides research grants of up

to $200,000 to put their research programs on solid footing and has also funded state-of-the-art research equipment.

NIH funding is important, to be sure, and Morrison’s recruits are quick to point to the factors at play in their success, such as great mentorship by senior faculty and grant writing tips and techniques from the UAMS Office of Grants and Scientific Publications. Also important is Morrison’s leadership, they said, with just the right mix of involvement in their research.

“One of the keys to the department’s success is that we interact really well with each other and the senior faculty,” Morrison said. “The interaction is infectious.”

The department’s work is pivotal for understanding and fighting back against a long list of increasingly dangerous pathogens, especially as antibiotics become less effective.

Voth, who after just 18

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Seated left to right: Richard Morrison, Ph.D.; Jason Stumhofer, Ph.D.; Lin-Xi Li, Ph.D.; Karl Boehme, Ph.D.; standing left to right: Jon Blevins, Ph.D.; Dan Voth, Ph.D.; J. Craig Forrest, Ph.D. Not pictured: Jia Liu, Ph.D.

months at UAMS earned a perfect score on an NIH grant application, is studying one of the most dangerous bacterial pathogens known — Coxiella burnetii. His work is creating excitement in the field in part because his program involves using donated living lung tissue, the best possible platform for gaining new insights into the pathogen.

Forrest earned another perfect

score in 2013 from the National Cancer Institute, which is supporting his promising work to prevent the herpes virus from causing cancer, a particular risk for people with weakened immune systems.

Although each researcher has his or her own lab and unique program, their offices in UAMS’ Biomedical Research I building are conducive to collegial communication,

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which sometimes prompts new collaboration.

Forrest said a conversation with Stumhofer resulted in a small grant that has led them to begin developing an application for an NIH grant.

“It’s cool synergy,” Forrest said. “When you get ideas and work well together, things just kind of take off.”

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C O M M U NITY

Josh Maloney, a UAMS pharmacy student on UAMS’ northwest Arkansas campus, performs a health screening for a Marshallese woman.

NORTHWEST ARKANSAS MARSHALLESE

Addressing Health Disparities in Northwest Arkansas

By Jon Parham

S

harlynn Lang’s mother has

struggled with diabetes for about 25 years, and in that time, Lang has lost family members and friends to diabetes and diabetes-related complications.

“Not just a few but many,” said the Springdale resident.

Lang, her family and friends are from the Republic of the Marshall Islands, a tiny chain of islands in the south Pacific. Drawn by economic 14

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opportunity and aided by the Compact of Free Association, which enables Marshallese to come to the United States without a visa or green card, many have settled in northwest Arkansas. The area is now home to the largest Marshallese population in the continental United States.

As a result of poor diet, lack of access to healthy foods, limited access to health care and other factors, nearly 50 percent of Marshallese ages 35 or older have type 2 diabetes, compared to less UNIVERSITY OF ARK ANSAS FOR MEDICAL SCIENCES

“

They have changed a lot of lives and are really making a difference,”

than 10 percent of the U.S. population.

Researchers and clinicians from the UAMS northwest Arkansas campus in Fayetteville are facilitating a multi-pronged approach to address health disparities in this minority community.

They are buoyed by more than $5 million in grants from the federal Centers for Disease Control (CDC) and Patient-Centered Outcomes Research Institute (PCORI) and a more recent grant of almost $195,000 from the Walmart Foundation.

“We want to drive down chronic disease problems and costs by helping those with diabetes in this underserved community,” said Peter Kohler, M.D., vice chancellor for the UAMS northwest Arkansas campus.

The UAMS team is teaching effective diabetes self-management skills that take into account the Marshallese family-centered culture. The team is also providing educational programs and health screenings and some medical care for diabetes patients at the recently opened student-led UAMS North Street Clinic on the Fayetteville campus.

“Access to care at the clinic brings together our commitment to addressing health disparities in our community with opportunities for our students to strengthen their skills through interprofessional education,” Kohler said.

The work uses a community-based approach that creates a partnership between researchers, clinicians and the community to address health disparities and improve health outcomes. In 2013, Pearl McElfish was appointed the director of research for UAMS' northwest Arkansas campus to begin building a research and community-based program infrastructure.

“We are working closely with the Marshallese families and community organizations to prevent, delay or moderate the complications of type 2,” McElfish said.

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Charity Jotai of the Marshallese community participates in a health screening with College of Nursing student Samantha Bolton (right).

Prior attempts to implement diabetes self-management education in Marshallese populations failed to produce even short-term results, McElfish said. Lang and Kohler noted that the Marshallese are often shy about their own health or problems.

Researchers designed a family-based model for diabetes self-management, based on the familycentered values of the Marshallese community.

It also is hoped successful techniques could be duplicated in other underserved populations SPRINGDALE in Arkansas, including the growing Hispanic community.

Lang, who moved to ARKANSAS Arkansas four years ago after living in Hawaii then California for almost 20 years, remembers clearly the night two years ago when she first met McElfish at a focus group on community health issues. She credited McElfish, Kohler and other faculty and students from UAMS for their commitment to helping her community.

“They have changed a lot of lives and are really making a difference,” Lang said. “My friends I’ve spoken to are hopeful. They’ve told me now they have a place they can go and be safe and get help.” www.uamshealth

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“

DISPARITIES

How we allocate resources in this country really affects health.”

Tackling the Economics of Health

By Spencer Watson

H

ealth disparities are expensive, and in a country that spends more than $3 trillion annually on health care, measuring those disparities, studying and quantifying them, helps craft policy solutions that will be costeffective in eliminating them.

“How we allocate resources in this country really affects health. And it’s very expensive. What we spend on health is about 20 percent of our gross national product, and we in Arkansas are about 1 percent of that, or $30 billion,” said J. Mick Tilford, Ph.D., a professor and chair of the Department of Health Policy and Management in the UAMS Fay W. Boozman College of Public Health.

In a recent study conducted on behalf of the Arkansas Minority Health Commission and modeled on a national study of the same topic, Tilford found more than $500 million in direct medical costs in the state of Arkansas due to racial and ethnic disparities.

Furthermore, nearly 80 percent of that figure is accounted for by disparities in the AfricanAmerican community, a higher percentage than the national average. The analysis equalized for things like income and insurance, then modeled the population based on health and projected health costs.

The resulting $500 million is money spent by individuals, the state, insurers and so on, and it’s money that could be spent on prevention instead, Tilford said.

“For example, compared to Caucasians, less money is spent on diabetes care in African16

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American populations, but more money is spent on amputations. That’s not a good outcome, and the cost of those amputations increases medical expenditures for those African-Americans.”

Another example is babies born before 34 weeks, where rates are twice as high for African-Americans as for Caucasians, Tilford said. Babies born so early require tremendous care and at great expense.

Though the study’s focus was on racial disparities, those disparities aren’t a factor of race alone. Geography and socioeconomic status also play a part – perhaps a larger part than race.

As Brian Smedley, Ph.D., vice president and director of the Health Policy Institute of the Joint Center for Political and Economic Studies put it when addressing the Sixth Annual National Conference on Health Disparities: “Your ZIP code is more important than your genetic code.”

Still, the findings point to a need for the state to focus more resources on intervention and provide some insight into knowing just how many resources can be put into those prevention efforts to make them cost effective.

In the long run, the result will be better public policy.

“Interventions can reduce health disparities and have an economic return in that the cost of interventions to reduce disparities is much less than the cost of the disparities themselves,” Tilford said.

“That’s an important economic finding. The real question is: what are the interventions that can be implemented that reduce these disparities and save money?”

That, however, is a matter for further research.

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Economics of Health The USA spends

3Trillion annually on health care

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Less money

is spent on diabetes care in African-American populations,

More

money

is spent on amputations

Rates are

Twice As High

%

of Gross National Product is spent on Health

for babies born before 34 weeks for African-Americans as for Caucasians

Arkansas is 1% or $30 Billion

500 Million 80%

but,

in medical costs in Arkansas due to racial and ethic disparities

disparities in the African-American community

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Your

Zip Code

is more important than your

Genetic Code www.uamshealth

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Jeffrey Pyne, M.D., demonstrates the possibilities of telemedicine with fellow VA researcher Dinesh Mittal, M.D. (on screen).

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VA MENTAL HEALTH

Identifying Bias In Access to Care

By Spencer Watson

S

ometimes it’s not enough for a doctor to know the right treatment for a patient.

Sometimes that puzzle includes other pieces, such as whether the treatment is delivered in the most comfortable, effective way. Still other times doctors must not hesitate to ask themselves whether they are letting preconceived opinions unconsciously get in the way.

These are just a couple areas of research being undertaken by Jeffrey Pyne, M.D., and Dinesh Mittal, M.D., both Central Arkansas Veterans Healthcare System physician-investigators who are also faculty members at UAMS. Pyne’s most recent work involves a study using telemedicine to provide telephone-based care management and televideo-based cognitive process therapy (CPT) — teaching patients with post-traumatic stress disorder skills to process their feelings — in the offices of their rural primary care doctors instead of requiring them to drive to a VA medical center.

“We want to bring specialty mental health care into non-specialty mental health settings in a way that is both acceptable to patients and providers and also effective,” Pyne said.

The results indicate that it is both. Not only were patients given the telemedicine option more likely to initiate and continue the treatment, symptoms were significantly lower compared to a usual treatment group.

“This particular trial was designed so that it could be exported to as many different settings as possible,” said Pyne. “Obviously, the VA is very interested in the fact that findings were positive and the association with CPT also fits with what the VA is doing in terms of training therapists to deliver evidence-based treatments, including CPT.” The result is a model that could be widely used

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and potentially expanded one day to even offer homebased therapeutic treatment via televideo.

However, it will always be up to doctors to listen to their patients, and that’s at the heart of research being done by Mittal, who in four papers has looked at the decision making of providers treating serious mental illness.

“We know that patients with serious mental illness have a very high mortality; they die about 15 to 20 years earlier than people who don’t have serious mental illness,” said Mittal. “There are disparities in physical health care for persons with serious mental illness in that they get less preventive care and less specialty care. Providers’ attitudes probably contribute to these disparities to some extent.”

Research has found that providers, much like the general public, have negative attitudes toward patients with serious mental illness. It indicates providers are somewhat negative toward persons with serious mental illness compared to those without serious mental illness. For example, providers generally expect patients with serious mental illness will be less likely to adhere to treatment and less likely to understand what education they are given.

This thinking exists even though studies show that patients with mental illness are no more or less likely to adhere to treatment. The result is that doctors are less likely, for example, to refer an obese patient with serious mental illness to a weight management program because doctors believe they won’t follow up even though most are able to similar to those who do not have mental illness.

“I don’t think providers do it consciously,” said Mittal. “It’s simply that doctors sometimes use prevailing beliefs about a whole population rather than scientific evidence and can forget to individualize care.”

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Julie Moretz, associate vice chancellor for patientand family-centered care, believes patients can help researchers solve problems.

NURSING PCORI

Drafting Patients as Research Partners

By Jon Parham

B

etter health outcomes is the goal of

community-based research. That research is most effective when patients are full partners, offering opinions about what direction the project should take.

UAMS nurse scientist Pam Williams has experienced that through her studies about the impact of rare disease on patients. A research project can be more productive when it involves affected patients — along with other clinical and community stakeholders — in every aspect of study design, data collection, participant recruitment and data analysis.

Williams is now working to develop a blueprint on how best to involve patients, clinicians, researchers and other stakeholders as full research partners to work toward a common goal from different perspectives.

Her work is funded by a two-year grant from the Patient-Centered Outcomes Research Institute (PCORI), a non-profit organization established by the federal Patient Protection and Affordable Care Act of 2010. PCORI’s mandate is to improve the quality and relevance of health information available to help patients, caregivers, clinicians, employers, insurers and policy makers make better health decisions that would be reflected in better health outcomes.

“The patient-centered style of research improves the relevancy of the outcome for patients and the impact of where research money is spent,” said Williams, J.D., Ph.D., R.N., an associate professor in the UAMS College of Nursing.

“When patients help shape the research 

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“

We used tools such as social media and distance health to bring them together.”

agenda and partner in the process, we will see new knowledge and behavior changes faster within their community.”

Williams pointed to her earlier PCORIfunded study of patients with alpha-1 antitrypsin deficiency (AATD), a rare genetic condition with two common, chronic conditions: emphysema and liver disease. Since these patients, like others living with a rare disease, are spread across the country (or world) they are often overlooked by the scientific community, which usually focuses on projects or health problems with the broadest impact or highest concentration of patients.

“By enlisting that community of alpha-1 patients as full partners in our work, we used tools such as social media and distance health to bring them together and find out their needs and what the patients believed we could or should be studying,” she said.

Patients, health care providers, caregivers and nonprofit organizations can be trained as research stakeholders to work together with research methods to solve problems, she said.

“We hope to see other patient communities following our model to develop partnerships with scientists to jump start work on patient-centered outcomes from research,” Williams said.

Williams’ collaborators include faculty in the UAMS colleges of Nursing, Medicine and Public Health. Also contributing to the effort is the Center for Distance Health and the UAMS Office of Patient- and Family-Centered Care, which is led by Associate Vice Chancellor Julie Moretz, who also serves as regional ambassador for the PCORI organization.

“Across the country, we know that a huge gap exists in the research community in how to work with patients, caregivers and community stakeholders — this type of partnership is new,” said Moretz, who also serves on PCORI’s Patient Engagement Advisory Panel.

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“Many patients may not understand the intricacies of scientific research, but who better than patients and their caregivers to be partners in these efforts so that we get it right based on the realities of their needs?”

UAMS investigators are working with patients and providers across the country to reach consensus about the best techniques for training community partners on participating in research.

Some people learn better by watching a video, others by participating in a webinar or a seminar, for example. Some like to give feedback in a town hall setting, some prefer a small group format.

Moretz and her team are assisting the project by helping identify patients and caregivers committed to improving patient- and familycentered care through sharing personal health care experiences.

UAMS has more than 80 patient/family advisors serving as partners who help make the entire care experience the best it can be. The advisors serve on committees and have direct input and influence on policies, programs and practices affecting health care and services.

“To our knowledge, this is the first project of its kind to take a systematic, evidence-based approach to develop training and define best practices to support all categories of potential research partners: providers, patients and nonprofit leaders,” said Jean McSweeney, Ph.D., R.N., interim dean and professor in the College of Nursing.

From this consensus, the team will develop detailed training modules. Then, three sets of community-based research partners will participate in and give feedback regarding training outcomes. The research team will evaluate evidence to determine which training practices were most valued by the partners and proved most effective, allowing for creation of the patientcentered research blueprint.

Added Moretz: “We want to teach patients and families how to work with researchers and clinicians, but we also are focused on how best to teach researchers/clinicians to partner with patients and families.”

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INBRE

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ED U C ATING NE W R ESEA R C HE R S

It really opened my eyes to the opportunities available in research.”

Student Fellowships Build Pipeline to Research Careers

By Jon Parham

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UAMS-led effort to strengthen the

biomedical research environment in the state is intended to pay off now and in the future.

Arkansas is one of 23 states to receive funding from a National Institutes of Health program — totaling $40.7 million since 2001 — that is being used to recruit research faculty to Arkansas universities, purchase needed scientific equipment and seek to cultivate future homegrown research talent by giving undergraduate students handson research experience.

The UAMS-based Arkansas INBRE program manages the initiative for partners that include the University of Arkansas, Fayetteville; University of Arkansas at Little Rock; Arkansas State University; Hendrix College; and others.

“Laboratory research is a vital link in finding new medical treatments that will ultimately improve the lives of Arkansans,” said Lawrence Cornett, Ph.D., vice chancellor for research.

“This INBRE funding has been a critical component for the continued development of biomedical research programs that are now conducting cutting-edge research and in aiding the recruitment of highly skilled and research 

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Lindsey Dayer, Pharm. D., became interested in research through an undergraduate summer fellowship.

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-focused faculty and students at these Arkansas partner institutions.”

The investment in the future — through the 10-week summer undergraduate research fellowships — is building a pipeline to guide interested Arkansas students toward graduate education and research careers. It’s an investment that is paying off.

Since 2002, 161 undergraduates have participated in the program.

“If we develop that interest in students as undergraduates, it increases the chances they will seek advanced degrees and then locate in Arkansas, which enriches our workforce, the state and the patients they could help through their work,” Cornett said.

Spending 10 weeks working in a UAMS research lab in 2003 solidified then-college student Lindsey Dayer’s plans to aim for pharmacy school.

Dayer, Pharm.D., now an assistant professor in the UAMS College of Pharmacy, recalled that like many of the undergraduates, the fellowship was her first time to be in a working lab. It was exciting to participate in hands-on work, injecting cells with a needle as part of a study, she said.

The program has tracked the journeys of the 161 research fellows following their experience. At least 79 of the 161 are now pursuing or working in research or medical-related careers. The largest number, 40, are in graduate school now, and five are doing postdoctoral research.

There are 16 former summer fellows in either medical, pharmacy or physical therapy school now with another six serving their medical residencies.

Four of the graduates — including Dayer — are college faculty members. Six are practicing physicians, two are dentists, two are pharmacists, two are medical laboratory scientists, one is a lawyer and still others are working in private industry.

“It’s been a tremendous success in promoting graduate education and biomedical research or health care careers,” Cornett said.

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While data on similar programs from the other states is not available, Cornett said the different groups do share best practices and successes and are in close contact.

“My sense is that we do well compared to the other states,” he said. “I’m confident that we are better than most.”

The summer fellowship program is actually one of three successful outreach efforts of INBRE, which stands for the Institutional Development Award (IDeA) Network of Biomedical Research Excellence. The INBRE’s outreach also includes faculty fellowships and an annual research symposium, all seeking to promote more Arkansas-grown research talent — and ultimately attract more research funding to the state.

“Having opportunities for students at the undergraduate level or faculty members from Arkansas colleges participate in research is important to Arkansas,” said Stephanie Gardner, Pharm.D., Ed.D., former dean of the UAMS College of Pharmacy, who moved July 1 to lead UAMS’ academic programs as provost. “These experiences spark interest among students who become our future scientists, clinicians and teachers.”

Dayer has become all three. She is teaching students in the College of Pharmacy while also working in the Palliative Care clinic of UAMS’ Winthrop P. Rockefeller Cancer Institute where she counsels patients on medications.

She also has been involved in a research project seeking to develop smartphone applications that would remind patients to take medications on time. She still credits her summer fellowship as a formative experience. As she has the chance to mentor students now, it’s an experience she would recommend.

“I had already been thinking about a health care career when I got the fellowship, but it really opened my eyes to the opportunities available in research,” she said.

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A diverse health care workforce improves both individual and population health.”

STUDENT DIVERSITY

Encouraging Diversity in Science and Health Care

By Spencer Watson

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s dean of the UAMS Graduate School, Robert McGehee Jr., Ph.D., takes pride in every student. But when degrees were awarded in December 2014, he said it was “a great day.”

What set it apart was seeing the first graduate of a program to recruit and graduate more doctoral students from underrepresented and disadvantaged groups “These students will be the leading researchers, educators and academic administrators of the future,” said McGehee, who co-directs the Initiative for Maximizing Student Development. “That, in turn, helps research. The more diverse the workforce looking at a particular problem, the more successful you can be at solving it.”

The five-year program was begun in 2009 through a $1.6 million grant from the National Institutes of Health. It recently received another $2.45 million grant that will allow it to continue through 2019.

“A diverse student body improves the educational process for everybody,” said program director Billy Thomas, M.D., vice chancellor for diversity and inclusion. “When you look at the educational process, the quality of the education is improved not only for students, but also faculty.”

The initiative uses grant funds to pay graduate 26

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students’ first two years of expenses, including tuition, fees and a stipend. After two years, like all other graduate students, these students take qualifying exams to move on to a mentor’s lab, where other grants support them.

“These are exceptional students, the best and the brightest and the most promising, and we start working with them early in their undergraduate careers,” said McGehee.

The program accepts three to five students a year and currently has 23 participants. Through the program, UAMS has forged a network of contacts nationally, but particularly at institutions in Arkansas and surrounding states like Mississippi and Louisiana to recruit these students. After five years, almost 90 percent of program participants are still enrolled at UAMS. “All the others who have gotten to that point have passed their qualifying exam and have gone on to a mentor’s lab pursuant to a Ph.D., which really says a lot about the quality of the applicants we’ve had,” said McGehee.

“The goal of this program is really to increase the number of students from underrepresented groups receiving a Ph.D. in biomedical research, thereby increasing in the future the number of underrepresented faculty members and leaders at universities and academic health centers,” said assistant program director Kristen Sterba, Ph.D. UNIVERSITY OF ARK ANSAS FOR MEDICAL SCIENCES

The 2015 graduation from the UAMS Graduate School reflects a diverse health care workforce.

And that makes for better health, Thomas said.

“In a broad sense, the importance of diversity, moving beyond the classroom, is that it’s beneficial to everyone involved. It makes for better health care workers in the end. Just by increasing the numbers of underrepresented students, we change the culture of the institution. And by UNIVERSITY OF ARK ANSAS FOR MEDICAL SCIENCES

doing that, we create a culture that’s more inviting and nurturing," he said.

“A diverse health care workforce improves both individual and population health and in the end closes the health and health care disparities gaps that exist in underserved communities.”

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INTERDISCIPLINARY BIOMEDICAL SCIENCE

Human Health Problems Require Multifaceted Approach

By Spencer Watson

By Spencer Watson

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arge problems in human health require researchers with a broad perspective. UAMS is working to ensure its Graduate School students are equipped to meet that challenge.

“We are working to develop a unified admission process in which every basic science graduate student is admitted to a centralized curriculum, then, depending on their interest, moves into a specific program or track, which will be interdisciplinary,” said Robert McGehee Jr., Ph.D., dean of the UAMS Graduate School.

“By doing that, we will be continuing both the national trend and the success of our own interdisciplinary program, which we launched in 2005,” 28

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McGehee said. “By 2016, all basic science students will be centralized during the first year so that everything is interdisciplinary.”

The reason for that, McGehee said, is based on the multidisciplinary nature of biomedical research.

“Life doesn’t exist within a single discipline. You’re not just a nervous system or a cardiovascular system. To address human disease requires a multidisciplinary approach.”

The Interdisciplinary Biomedical Sciences (IBS) Graduate Program, currently with 55 students enrolled, was developed to provide just such a broad perspective by exposing students to more expansive fields of study while still  UNIVERSITY OF ARK ANSAS FOR MEDICAL SCIENCES

MOLECULAR BIOLOGY

INTERDISCIPLINARY BIOMEDICAL SCIENCE PHYSIOLOGY

BIOCHEMISTRY

MICROBIOLOGY

IMMUNOLOGY

IMMUNOLOGY

TOXICOLOGY PHARMACOLOGY

BIOPHYSICS

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“

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Life doesn’t exist within a single discipline.”

remaining focused on research.

“We want our students to be really passionate about doing research,” said William D. Wessinger, Ph.D., director of the IBS Graduate Program.

“The Ph.D. degree is one that focuses on research. A person trained with a Ph.D. is someone who can identify a critical question that needs to be answered to fill a gap in our knowledge base, who knows how to formulate hypotheses and design experiments aimed at filling that gap, and who knows how to communicate their findings to others.”

Broadening the multidisciplinary approach to all basic science students, said McGehee, will attract exactly the kinds of scientifically curious minds UAMS aims to recruit.

“I think it will further increase the quality of applicants, but also serves them well in offering more flexibility in finding their track or program. It also increases the opportunity to successfully compete for extramurally funded training programs,” he said.

That flexibility builds on that of the existing IBS Program, which allows students access to a wide range of faculty mentors.

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study in the lab of a faculty mentor in that department.

However, within the IBS Program, students might end up doing their research in any of the basic science departments, or in any of the many other places where research is conducted at UAMS such as the Winthrop P. Rockefeller Cancer Institute, the Psychiatric Research Institute, or the Donald W. Reynolds Institute on Aging, or even conducting their research in one of the clinical departments.

“I think where this program differs is that the options for students are much broader, which is why we have students in many different areas on and off campus,” Wessinger said.

“Their first year they have the opportunity to do research rotations a little more broadly, before they have to decide what they want to do for the next four or five years. I think they get some comfort out of knowing that they have that flexibility.”

Likewise, labs often benefit from the perspective students can bring – particularly research labs in clinical departments that don’t have as easy access to graduate students.

“Everything gets improved because students are around,” Wessinger said. “The whole lab can be invigorated by the challenges of the questions students ask. All of a sudden

they’re seeing things from a different perspective and that’s a value that students can bring.

Sometimes it changes the culture of the laboratory.”

A subset of students in the IBS Program is students who are concurrently pursuing dual degrees in medicine and research—the M.D./Ph.D. students. In the dual degree path, students complete the first two years of medical school, then over the next three to four years complete the Ph.D. research component before returning to medical school to finish their final two years and graduate with both degrees.

“Because it’s such a long program, our program is very small. We’ve only got around 20 M.D./Ph.D. students, and we only admit three or four a year.

Individuals get a lot of attention, and we can have flexible research training that really meets students’ interests and needs,” Wessinger said.

The ultimate goal of the M.D./Ph.D. Program is to put more physician-scientists into the biomedical research workforce, which is a widely recognized need. Ideally, some of these physician-scientists will come back to UAMS for a career in academic medicine that combines patient care with medical research.

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E C ONO M I C R ET U R N

Innovative research on Arkansas campuses has been an economic pump.”

ARKANSAS RESEARCH ALLIANCE

Recruiting and Retaining Research Leaders

ARKANSAS

By Ben Boulden RESEARCH ALLIANCE

T

he Arkansas Research Alliance (ARA)

is looking for entrepreneurial research leaders who are potential job creators.

It found such a match in Peter Crooks, Ph.D., D. Sc., who was recruited to UAMS in 2011 to chair the Department of Pharmaceutical Sciences in the College of Pharmacy.

A Crooks innovation — a breakthrough gel for the treatment of a form of lymphoma branded as Valchlor — won FDA approval in 2013, and Crooks holds more than 69 issued U.S. patents, with 185 pending, including about 30 involving his UAMS work.

“Up to this point, I’ve started seven companies,” Crooks said. “Every one of them has been relatively successful.”

ARA Scholars The alliance was established in 2008, and the ARA Scholars program was launched in 2010 to bring entrepreneurial scholars like Crooks to Arkansas. It is funded with money from the state of Arkansas, grants from the U.S. Food and Drug Administration and dues paid by its public and private partners whose representatives serve on its board.

The program recruits highly respected thought leaders in scientific research from outside the state with the goal of adding value to existing research programs through collaboration, innovation and eventually commercialization that brings jobs and businesses to Arkansas. 

Arkansas Research Alliance Board of Trustees ARA is governed by a board of trustees comprised of chancellors from Arkansas research universities and business leaders from across the state: chairman Jeff Gardner, former president and CEO of Windstream; treasurer Robert L. Shoptaw, retired CEO of Arkansas Blue Cross Blue Shield; University of Arkansas at Pine Bluff Chancellor Laurence Alexander, Ph.D.; University of Arkansas at Little Rock Chancellor Joel Anderson, Ph.D.; University of Arkansas for Medical Sciences Chancellor Dan Rahn, M.D.; Ritter Arnold, president of Ritter Agribusiness Holdings Inc.; Hal Carper, group vice president of research and development, logistics and technical services at Tyson Foods; R. Andrew Clyde, president and CEO of Murphy USA Inc.; Kristi Crum, president - South Central Region

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at Verizon Wireless; Ray C. Dillon, president and CEO of Deltic Timber Corporation; Ed Drilling, president of AT&T; University of Arkansas, Fayetteville Chancellor David Gearhart, Ph.D.; Sonja Hubbard, CEO of E-Z Mart Stores Inc.; Arkansas State University Chancellor Tim Hudson, Ph.D.; Roger W. Jenkins, president and CEO of Murphy Oil Corp.; Tommy May, chairman and CEO of Simmons First National; Hugh T. McDonald, president and CEO of Entergy; Charles Nabholz, president and CEO of The Nabholz Group; John Roberts, president and CEO of J.B. Hunt Transport Services Inc.; Reynie Rutledge, president of First Security Bank; and Rick Webb, senior vice president, global business processes at Walmart.

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The end game is to create good-paying, knowledge-based jobs.

“Innovative research on Arkansas campuses has been an economic pump,” said Jerry Adams, president and CEO of the Arkansas Research Alliance. “We’re trying to get more structure and formation around research to elevate the thought process and recognize these talented people.”

Arkansas’ five research universities — UAMS, the University of Arkansas at Little Rock, the University of Arkansas at Pine Bluff, Arkansas State University in Jonesboro and the University of Arkansas, Fayetteville — are a part of the ARA Scholars Program.

For a recruit to qualify as a scholar, he or she must work in one of nine strategic focus areas.

Those areas range from food processing and safety and nano-related materials to personalized health research sciences and behavioral research for chronic disease management.

Of the five researchers the ARA has recognized as scholars, two others besides Crooks are at UAMS: Gareth Morgan, M.D., Ph.D., director of the UAMS Myeloma Institute; and Daohong Zhou, M.D., a professor in the Division of Radiation Health of the UAMS College of Pharmacy’s Department of Pharmaceutical Sciences.

When each of them was recruited to UAMS, it was with the understanding he would be named an ARA scholar and receive a $500,000 three-year grant to help fund his research. Zhou was one of two inaugural ARA Scholars named in 2010.

Crooks was named in 2011 and Morgan in 2014.

ARA Fellows In December, the alliance expanded its program to recognize university research leaders already working in the state. One its first five ARA Fellows is Laura James, M.D., a pediatrician, researcher and director of the UAMS Translational Research Institute.

UAMS Chancellor Dan Rahn, M.D., serves on the alliance’s board and before coming to Arkansas 32

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served on the board of Georgia Research Alliance after which the Arkansas Research Alliance was modeled.

“Research into new treatments, drug development, medical devices and new technologies at UAMS and the state’s other research universities has led to the formation of new companies that generate good paying jobs and economic development,” Rahn said. “The ARA is a key part of that effort.”

Adams said Arkansas already has strength in national and international fields such as nanomaterials and drug development.

Zhou’s research focuses on radiation biology and normal tissue response to cancer therapy.

Crooks is working to discover and develop new cancer treatment drug agents to improve outcomes after radiation therapy and medication to treat acute and chronic pain.

Morgan hopes to discover and develop new agents for the treatment of multiple myeloma and explore new genomic treatment approaches.

James is working to develop a better way to identify acetaminophen poisoning that leads to liver injury.

The Impact The ARA expects to recognize more scholars and fellows and bring them together annually to envision what new innovations will be on the horizon along with the economic opportunities they might offer Arkansas, Adams said.

The meeting will help devise state incentives for research and development as well as removing barriers that impede getting innovative new products and services to market.

“The challenge at a medical school is getting it through the clinical trials to get it to have an economic impact, which is several years away,” Adams said. “We hope to encourage university researchers to look at solutions and innovations. We have to be aggressive about it.

Its impact already has been surprisingly high.

It’s added a collaborative energy across these five campuses.”

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From left: Gareth Morgan, M.D., Ph.D.; Laura James, M.D.; Peter Crooks, Ph.D., D. Sc.; and Daohong Zhou, M.D., were selected for the Arkansas Research Alliance program.

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“

A key focus also is boosting economic development for Arkansas and its people through these innovations.”

BIOVEN Business Incubator Helps Start-ups Succeed

By Ben Boulden

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earning about a new scientific breakthrough can be exciting. Learning that it may not positively affect your life for many years to come can be frustrating. UAMS BioVentures, a biomedical business incubator, works to shorten that wait.

Through the companies UAMS BioVentures helps germinate and grow, it increases the access of people to advances in medicine and technology, making concrete the abstract ideas and innovations born in the university’s laboratories.

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“That really is our main purpose,” said Nancy M. Gray, Ph.D., UAMS BioVentures director. “A key focus also is boosting economic development for Arkansas and its people through these innovations.”

By every key economic development measure, UAMS BioVentures is succeeding. More than 20 companies are active and supported by it.

Together, the companies have attracted more than $106 million in investment and employ about 250 people. Here’s a look at six.  UNIVERSITY OF ARK ANSAS FOR MEDICAL SCIENCES

NTURES ANGEL EYE Established in 2013, Angel Eye Camera Systems has developed and marketed camera systems that use the latest communications technology to provide parents and family a secure, long-distance video and audio connection to their newborns in the neonatal intensive care unit.

Once a hospital is outfitted with Angel Eye, parents and anyone they permit can see the baby on their computers or mobile devices anytime while the infant is hospitalized.

The company’s systems are in hospitals in Arkansas, Massachusetts, Missouri, Texas, Pennsylvania and New York with others pending.

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SAFE FOODS Many people remember a discovery made 20 years ago at UAMS that cetylpyridinium chloride was effective in eliminating E. coli, listeria and salmonella from poultry. Made by professors in the College of Pharmacy’s Department of Pharmaceutical Sciences, the discovery helped give birth to the Safe Foods Corporation and its Cecure-brand antimicrobial agent.

Food processors and producers use Cecure to cleanse food surfaces, which helps control food-borne pathogens and substantially extend the shelf-life of foods.Royalties have generated almost $1 million for UAMS, the College of Pharmacy and the inventors.

ACETAMINOPHEN TOXICITY DIAGNOSTICS Using research from UAMS and the Arkansas Children’s Hospital Research Institute, Acetaminophen Toxicity Diagnostics is developing a rapid point-of-care diagnostic dipstick test for detecting acetaminophen poisoning in patients.

Excessive doses of acetaminophen (Tylenol) are the leading cause of acute liver failure in the United States, but current laboratory tests do not capture many cases. Recent tests showed the new dipstick could accurately diagnose acetaminophen overdose. Laura James, M.D., is the company’s chief medical officer and is director of the UAMS Translational Research Institute.

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SIGNAL GENETICS Signal Genetics in 2010 acquired an exclusive license to technologies developed at the UAMS Myeloma Institute. The technologies can predict the stage, calculate the odds of relapse and lead physicians to the best treatment for people with multiple myeloma.

Based on more than 20 years of clinical research involving 10,000 multiple myeloma patients who received care at UAMS, MyPRS (Myeloma Prognostic Risk Signature) is its main product. It offers the test out of its Little Rock lab.

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INTERVEXION THERAPEUTICS InterveXion Therapeutics is developing a treatment for methamphetamine abusers. The treatment makes use of monoclonal antibodies or vaccines against methamphetamine that work to help a drug abuser stay in treatment.

The antibody binds the methamphetamine and keeps it from going into the brain, so users don’t get the high they are expecting.

“BioVentures has had a big impact on our business because it’s been our home since the beginning,” said Misty Stevens, Ph.D., M.B.A., operations director for InterveXion Therapeutics.

“They have provided a lot of help with the patenting.”

RX RESULTS Little Rock-based RxResults was founded

by Tery Baskin in late 2008 with support from BioVentures. It was formed to commercialize the new innovative pharmacy benefit model developed by the Evidence-Based Medicine Center (EBRx) at the UAMS College of Pharmacy.

This program was designed to reduce prescription drug costs for employers and their employees while ensuring the employees receive the most effective, high-quality medicines available. It recently drew $4 million in capital investment and in the next 18 months expects to add 20 to 30 more jobs to its work force of 10.

“BioVentures provided the framework for the start of the process,” said Tery Baskin, Rx Results CEO and president. “We worked closely with BioVentures staff on our business plan.”

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The Future Two of the newest companies in development at BioVentures are Naptime Academy, which produces training videos for child care professionals that can be viewed on a smart phone, tablet or computer with Internet access, and Biobotics Solutions, which plans to market a robotic pathology testing device that is designed to greatly reduce human error in forensic examinations and tests.

“There are a remarkable number of innovative ideas and technology concepts that come out of the research and even the day-to-day activities of doctors, scientists, nurses and staff at the UAMS Medical Center and colleges,” Gray said. “Capturing the breadth of these and developing the appropriate commercialization path is the key mission of BioVentures.” www.uamshealth

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LITTLE ROCK TECHNOLOGY PARK

Creating a ReseachTechnology Center

By Elizabeth Caldwell

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ach rents a tiny working space —

a desk and a chair, really — by the month; but these dozen or so budding entrepreneurs are hoping to make it big in research and technology.

The small teams, sometimes just a one-person startup, are the first fruits of the Little Rock Technology Park, which set up operations in early 2015 in a downtown building on Markham Street. The space is temporary, as the park

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moves forward with negotiations on its proposed permanent home on Main Street.

The park is an ambitious and forward-thinking project created in 2007 by the Arkansas Legislature to acquire, develop and manage a researchtechnology center in Little Rock.

Partners in the park are the city of Little Rock, the University of Arkansas at Little Rock, UAMS and Arkansas Children's Hospital.

“The goal of the park is to grow the ability of the UNIVERSITY OF ARK ANSAS FOR MEDICAL SCIENCES

Drawing by: Wittenberg Delony & Davidson Architects

“

universities to do research, and within that, to keep that talent in Arkansas,” said Park Director Brent Birch.

The space on Markham is geared to the startup entrepreneurial community, he said, but the future home of the park is intended to include Kevin Navin researchers from UAMS and UALR who will be translating their biomedical and technology discoveries into economic drivers for the institutions and the city.

The park also houses the Arkansas Venture Center, which provides mentoring and networking opportunities for the tenants, including educational and social events.

Creating a space where researchers, entrepreneurs and business start-ups can interact, both coincidentally through shared space and at planned events, creates a “high-density district UNIVERSITY OF ARK ANSAS FOR MEDICAL SCIENCES

It helps boost the innovation economy and the knowledge-based economy.”

of innovation” conducive to technology companies whose skills sets may overlap or may end up needing each other’s services, Birch said.

And the city gets a better job environment for citizens and the ability to keep these ideas local.

“It helps boost Arkansas’ growing innovation economy,” Birch said. “Talent is a big piece of it. Say I have a great idea and want to start a company, but are there people in Little Rock who I can hire to do what I need to get my company off the ground? This will help foster the retention of talent.”

The park’s seven-member board is appointed

by UAMS Chancellor Dan Rahn, M.D., UALR Chancellor Joel Anderson, Ph.D., and Little Rock Mayor Mark Stodola.

Members of the board are Chairman Mary L. Good, Ph.D., retired dean of the UALR Donaghey College of Engineering and Information Technology; Tom Butler, retired UAMS vice chancellor for administration and governmental affairs; Darrin Williams, Southern Bancorp CEO and former state representative; Kevin Zaffaroni, Acxiom Corp. senior vice president for information technology; Jay Chesshir, CEO of the Little Rock Regional Chamber of Commerce; Dickson Flake, a realtor with Colliers International; CJ Duvall, retired from Allied Wireless Communications Corp.

The entire Phase 1 effort of acquiring the buildings, renovating and seeking tenants could take two to three years, Birch said. After that there will be options depending on need, including a possible lab facility.

“We’re trying to become that source that fosters the commercialization of research. A lot of companies don’t get off the ground due to all kinds of hurdles. The Little Rock Technology Park will ensure that failure won’t be because of lack of facilities and resources in the central Arkansas marketplace. Our project will create a cluster of innovative people bettering our local economy on various fronts.” www.uamshealth

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ONGOING R ESEA R C H

SURGEON RESEARCHERS

“

If we can find better ways to operate and give our patients a better chance at recovery, we are happy.”

From the Operating Room to the Research Lab

By Susan Van Dusen

A

career in surgery undoubtedly leads to long hours and high stress. So why would a surgeon choose to add medical research to his or her already hectic schedule?

For pediatric head and neck surgeon Gresham Richter, M.D., the reason is simple.

“I want to find a way to help patients without putting them through the ordeal of surgery,” he said.

For Richter that means establishing a research lab and tissue bank to investigate potential drug treatments for aggressive arteriovenous (AVM) and lymphatic vascular malformations, incurable blood vessel disorders that if left untreated, grow uncontrollably by infiltrating and destroying tissue.

Housed at Arkansas Children’s Hospital Research Institute, the tissue bank stores samples collected from patients during surgical procedures and uses them for biomedical research. Since it was established in 2009, Richter’s research team is already seeing promising results.

“Based on our research, we’ve starting using a simple antibiotic to control AVMs and are having some success,” said Richter, who see patients at Arkansas Children’s Hospital (ACH) and is endowed chair, vice chief of pediatric otolaryngology and associate professor in the UAMS College of Medicine’s Department of Otolaryngology-Head and Neck Surgery.

One of the biggest challenges for a surgeon who wants to conduct research is time management. Pediatric urologist Stephen Canon,

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M.D., begins his day at 4 a.m. to pursue research interests and maintain his surgical schedule. “It’s about maximizing time, focusing on what you can do and multitasking,” he said.

Canon, associate professor and program director of pediatric urology in the College of Medicine Department of Urology, left private practice to join UAMS in part because of its large research infrastructure. He practices at ACH and specializes in correcting hypospadias, a condition in which boys are born with the opening of the urethra on the underside of the penis instead of the tip.

The work of Canon’s team, which includes research assistant Carol Sikes, R.N., has shown a high prevalence of hypospadias in Arkansas. “We are seeing milder forms of the condition becoming better recognized and driving up diagnosis rates,” Canon said.

He wants to follow patients long term to better understand their outcomes. “This is a career-long interest of mine,” he said.

Fellow UAMS physician Michiaki Imamura, M.D., Ph.D., also understands the challenges of incorporating research into his busy schedule.

As chief of Pediatric Cardiothoracic Surgery and professor in the College of Medicine Department of Surgery, Imamura spends 95 percent of his time treating patients with heart disease or heart failure, from newborn babies through adults with congenital heart conditions.

Due to his high patient load, Imamura’s research interest in improving heart valve UNIVERSITY OF ARK ANSAS FOR MEDICAL SCIENCES

Takeshi Shinkawa, M.D., sews an artificial blood vessel he and Michiaki Imamura, M.D., Ph.D., developed for use in heart valve replacement.

replacement outcomes is primarily led by his colleague Takeshi Shinkawa, M.D., assistant professor in the Department of Surgery.

When cardiac patients undergo heart valve replacement, it’s common for their bodies to reject the new valve. With Imamura’s leadership, Shinkawa has developed a method of constructing artificial blood vessels containing a valve structure that lessens the chance of rejection.

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“We are now exclusively using the heart valves that Dr. Shinkawa constructs by hand,” Imamura said, adding that Shinkawa presented findings of their research at a meeting of the Society of Thoracic Surgeons in early 2015.

“If we can find better ways to operate and give our patients a better chance at recovery, we are happy,” Shinkawa said.

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ARKANSAS CHILDREN’S NUTRITION CENTER

Using Research Findings to Improve Children’s Development

By Katrina Dupins

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The research is not just about preventing disease, it is about optimizing outcomes in children.

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hat a pregnant woman eats can affect the development of her child before and after he or she is born with consequences that may extend even into adulthood.

Researchers at the Arkansas Children’s Nutrition Center are finding that proper nutrition maintains health through more complicated ways than previously imagined. Scientists at the center are looking at how nutrition interacts with a person’s health from the beginning stages of life through preadolescence using measures to characterize these relationships that span the molecular to the behavioral.

The Arkansas Children’s Nutrition Center is one of only two USDA children’s nutrition centers in the country, and the only one relating nutrition, cognition and brain function in developing children. Since its 1994 establishment under founding director Thomas Badger, Ph.D., the center has become a global leader among nutrition research programs.

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partnership between UAMS, the USDA-Agricultural Research Service, and Arkansas Children’s Hospital Research Institute, the center’s goal is to use research findings to improve children’s development as well as reduce the risk of disease.

Leading that effort is Sean Adams, Ph.D., who was named center director in July 2014.

Adams is professor and chief of the Developmental Nutrition Section in the Department of Pediatrics in the UAMS College of Medicine.

“Nutrition and physical activity in adulthood are very important, of course,” Adams said. “But to think that we could influence someone’s life and health by helping support their mother’s health, that’s a pretty big deal.”

Adams said that by looking into maternal health and early childhood nutrition, researchers have an opportunity to make a connection between health and nutrition that can have both immediate effects as well as effects later in life.

Adams comes to UAMS

from the University of California, Davis. His research investigates metabolic physiology and the causes and consequences of obesity and metabolic disorders.

Adams conducts innovative research into insulin resistance and metabolic profiles associated with obesity and type 2 diabetes.

One of his key goals as director is to understand how best to apply what researchers are learning at the lab bench and in studies with human volunteers back to a clinical or public setting, so that it can have a positive impact on a child’s life before he or she is even born.

Adams says the more researchers learn about those fundamental processes, the better advice clinicians will be able to provide expectant mothers about their diet and physical activity.

The research is not just about preventing disease, it is about optimizing outcomes in children.

“A lot of the research is

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Sean Adams, Ph.D., measures a child’s body composition with a machine called a Bod Pod.

related to cognitive function and brain biology,” Adams said. “That we may be able to optimize function in addition to disease prevention is pretty exciting. The two go hand in hand.”

As an example of potential dividends, the center’s studies on

cognitive development should help explain the relationship between diets and optimizing attention and learning while in school.

Part of the center’s signature research includes the influence of maternal diet and physical activity, obesity and

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postnatal feeding on children’s physiological, psychological and cognitive development. The studies are being conducted by a nationally recognized team of UAMS Department of Pediatrics faculty, backed by top-tier support scientists and collaborators. www.uamshealth

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CHILD INJURY PREVENTION

Research Center Supports Many Aspects of Child Health

By Elizabeth Caldwell

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TVs are Mary Aitken’s passion.

That’s not unusual in a rural state such as Arkansas where children sometimes are riding an all-terrain vehicle while still in elementary school.

But you won’t find Aitken, M.D., a professor of pediatrics in the UAMS College of Medicine, out riding one in the deer woods.

Instead, she and her team have devoted the last nearly 20 years to educating parents so their child doesn’t become one of the 75 to 100 children admitted each year to Arkansas Children’s Hospital (ACH) injured while driving an adult-sized ATV. That’s just one of the issues for Aitken and her team of researchers and health educators.

As director of the Injury Prevention Center at ACH, she sees a great need to reduce the number of unintentional injuries that plague Arkansas children — from motor vehicle crashes to prescription drug overdoses.

Still, her interest in protecting children extends further. Aitken directs the Center for Applied Research and Evaluation (CARE) in the UAMS Department of Pediatrics, which has ongoing research into not only pediatric injury prevention, but child health services and child health, development and nutrition.

While the research centers on children, “there has to be a family approach to everything we do,” Aitken said.

She and other UAMS researchers with CARE are making headway on a number of difficult issues that is improving the health of children in Arkansas and the nation. CARE includes faculty representing pediatrics, epidemiology, medical sociology, health services research, and nutrition.

Patrick H. Casey, M.D., a professor of pediatrics and psychiatry, is working on food security and access to healthy foods. He is the principle investigator on a multisite research study

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that has found that about 20 percent of children seen in the ACH Emergency Department have no reliable and routine access to acceptable food. In response, ACH has been providing free lunches to children every day since last summer, totaling more than 15,000.

Judith L. Weber, Ph.D., a professor of pediatrics, is co-directing a research program studying the nutritional status of children who are obese, and working with school-based gardens as a way to educate young people about healthy food.

Dennis Kuo, M.D., associate professor of pediatrics, is setting out to develop personal care teams for children with special health needs UNIVERSITY OF ARK ANSAS FOR MEDICAL SCIENCES

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through the patient-centered medical home concept. He, along with CARE researchers James M Robbins, Ph.D. and Anthony Goudie, Ph.D., have demonstrated cost savings and reduced hospitalization for children with more than one chronic condition when they are served by a specialized, multidisciplinary clinic.

Regarding injury prevention, Aitken said Arkansas has made remarkable progress in having fewer people, especially teens, killed or injured in car crashes.

“Motor vehicle safety in general is a real success story, and Arkansas has seen a dramatic 57 percent reduction in teen driver fatalities UNIVERSITY OF ARK ANSAS FOR MEDICAL SCIENCES

There has to be a family approach to everything we do.”

over the past several years.”

She attributed it to laws that require young drivers to get more experience before obtaining full driving privileges as well as improvement in car designs and recognition for the need for more supervised training.

And those ATV accidents? The numbers are still discouraging, but she believes there is increased awareness of safety issues.

“We’re getting through to parents that children should not ride adult-sized ATVs and all riders should always wear a helmet. It’s a work in progress.”

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CANCER VACCINE

Clinical Trials Induce Antibody Response

By Susan Van Dusen

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The vaccine was shown to induce antibody responses that are toxic to breast cancer cells.

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or breast cancer survivors,

the possibility of their disease returning is a frightening reality. That’s why scientist Thomas Kieber-Emmons, Ph.D., has spent his career searching for ways to prevent recurrence and give patients a much-needed peace of mind.

His years of study have led to the development of a vaccine that is showing great potential not only to prevent the recurrence of breast cancer, but also to shrink tumors in other cancer patients.

The vaccine, which is a first of its type tested in humans, was shown to induce antibody responses that are toxic to breast cancer cells during a phase 1 clinical trial conducted with advanced-stage breast cancer patients at the UAMS Winthrop P. Rockefeller Cancer Institute.

The UAMS Cancer Institute and its affiliated Highlands Oncology Group in northwest Arkansas are the main facilities in Arkansas to offer phase 1 and phase 2 clinical trials, which are the early testing phases used by researchers to determine a new therapy’s safety, dosage and side effects. Before a drug can enter clinical trials the research must be approved by the FDA, which carefully monitors each phase of the trial to ensure sound scientific and ethical practices.

The trial of Kieber-Emmons’ vaccine was conducted exclusively with UAMS breast cancer patients, offering them access to a new therapy unavailable anywhere else in the world.

“The participants in our phase 1 trial had significant disease, including one whose cancer had metastasized to her brain. It looks like the vaccine in combination with her standard therapy had a positive impact in this patient in particular,” said Kieber-Emmons, professor of www.uamshealth

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pathology in the UAMS College of Medicine.

The phase 1 clinical trial, conducted at UAMS

by Laura Hutchins, M.D., was primarily designed to evaluate how well patients tolerated the new vaccine, any adverse side effects and the effect on inducing immune responses that kill cancer cells in patients. A phase I trial enrolls a small number of patients, sometimes a dozen or fewer.

Kieber-Emmons’ collaborator on the study, Hutchins is professor in the Division of Hematology/Oncology in the UAMS College of Medicine and director of clinical research at the UAMS Cancer Institute.

Now in a phase 2 clinical trial, the vaccine is being tested in a greater number of patients at UAMS and Highlands to determine its effectiveness and safety. The vaccine is being tested in conjunction with chemotherapy in women with earlier stage disease to see if it helps trigger the tumor to shrink prior to surgery. A collaboration between UAMS and Highlands allows patients to receive the benefits of clinical trials while undergoing treatment close to home.

If it continues to show positive results, a phase 3 clinical trial will follow in which the vaccine will be used on hundreds or thousands of patients at multiple sites to compare its effectiveness with standard treatment. On average, it takes about eight years once a cancer drug has entered clinical trials for it to become FDA approved for widespread use.

In addition to its potential for breast cancer patients, the vaccine will be tested in inoperable lung cancer patients and plans are underway to test the vaccine in UAMS patients with melanoma and a type of brain cancer called glioblastoma.

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OSTEOPOROSIS

Age, Not Decreased Estrogen, to Blame

By Katrina Dupins

H2O2

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“ Y

The cause of osteoporosis could be very similar to the cause of other diseases of advanced age.”

ears of research in osteoporosis at

UAMS have paid off with a series of discoveries that are changing the way doctors and the public think about the bone-weakening disease.

Researchers at the UAMS Center for Osteoporosis and Metabolic Bone Diseases have shown during the last twenty years that osteoporosis is not just a disease caused by menopause, a stage when women stop producing as much estrogen.

“Estrogen loss is only one of many very important factors. We now know that it is not just a disease of women. It affects men, too,” said Stavros Manolagas, M.D., Ph.D., the center’s director, distinguished professor of internal medicine and director of the Division of Endocrinology and Metabolism in the UAMS College of Medicine.

“The idea in the beginning was, ‘If you lose estrogen, you get osteoporosis,’” he said. “The conclusion was to give estrogen to osteoporosis patients. We later discovered that estrogen causes adverse side effects including breast cancer and heart disease.”

More than 53 million people in the United States either have osteoporosis or are at high risk due to low bone mass. Osteoporosis is the major cause of fractures in people older than 50.

Researchers say one in two women and one in four men over 50 will have an osteoporosis-related fracture in her or his lifetime. The costs associated with osteoporosis between 2005 and 2025 are expected to be $474 billion, according to the latest U.S. Bone and Joint Burden Report.

UAMS researchers have found that advancing age, beginning as early as a person’s 30s, causes a series of changes in bone that eventually decrease bone mass and weaken bone. Their work, according to Manolagas, has caused a paradigm

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shift from the “estrogen-centric” account of how osteoporosis develops to one in which age-related mechanisms intrinsic to bone are key.

In another recent discovery, the UAMS investigators found that an increase in hydrogen peroxide production that comes with aging contributes to a progressive imbalance in which the body removes more old bone than it produces new bone.

More important, the UAMS group and collaborators at the University of Washington in Seattle have found that reducing hydrogen peroxide prevents not only osteoporosis but also age-associated energy imbalance, diabetes, some heart diseases, Alzheimer’s and hearing loss in mice. Manolagas believes that decreasing the production of hydrogen peroxide in cells may be a rational approach to the treatment of osteoporosis in humans.

“The cause of osteoporosis could be very similar to the cause of other diseases of advanced age like Alzheimer’s, high cholesterol and heart disease,” Manolagas said. “That’s exciting because our work shows that there is the potential to develop therapies that, for the first time, will treat multiple diseases at the same time.”

Manolagas said that a big part of the success of the UAMS Osteoporosis Center is that the researchers work as a team.

Since the UAMS Center for Osteoporosis and Metabolic Bone Diseases began in 1994, it has received more than $70 million in extramural funding. In 1999, with the help of UAMS BioVentures, Manolagas founded Anabonix Inc. to develop and commercialize drugs for osteoporosis. This company operates now in Cambridge, Massachusetts, under the name Radius Health Inc. Since June of 2014 Radius is publicly traded in NASDAQ – the first in UAMS history. www.uamshealth

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RADIATION INJURY

Protecting People on Earth and in Space

By Ben Boulden

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rom the Earth to beyond the sky, UAMS College of Pharmacy scientists are searching for better ways to protect people from radiation injury.

A UAMS research team, led by Marjan Boerma, Ph.D., is investigating the 50

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effects of space radiation on cardiovascular health. One of the countermeasures against radiation injury in which the research team is interested is tocotrienol, in the vitamin E family.

Another team, led by Martin Hauer-Jensen, M.D.,

Ph.D., is working with experimental models testing a new drug, SOM230, to treat gastrointestinal injuries after radiological or nuclear accidents or terrorist attacks.

In Space Boerma, associate professor in the Department of Pharmaceutical Sciences’ Division of Radiation Health, in 2014 was awarded a three-year $6 million grant by the National Space Biomedical Research

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“

We also have been asked to look at it for prophylactic use by the military.”

by whether an astronaut is exposed outside a space station or inside one. Another consideration is in regard to pure physics — the energy of the particles, how many are in the space environment being studied and what their effects are in combination with other particles and radiation.

Recently, collaborators at Loma Linda University in Loma Linda, California; Georgetown University in Washington, D.C.; and the University of Arizona in Tucson, Arizona, met at UAMS. “We were able to talk through some of these challenges,” Boerma said.

“We’re much closer to a consensus now.”

On Earth Institute (NSBRI) as part of the newly formed Center for Space Radiation Research based at UAMS. “We’re still working on setting up all the experimental models,” she said. “Radiation in space consists for a large part of a variety of charged particles.

We’ve had some interesting discussions in the group and at NASA about how to best model the radiation that astronauts are exposed to in space.”

The question is complicated

Meanwhile, Hauer-Jensen’s research team is finishing up work with its experimental models.

“We’ve seen some survival benefit from this drug,” said Hauer-Jensen, associate dean for research and director of the Department of Pharmaceutical Sciences’ Division of Radiation Health. “Now, we’re assessing if the benefit is stronger whether you administer the drug before or after radiation exposure, and how long before or after.”

In the fall of 2013, UAMS

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signed two new contracts worth more than $8.5 million with the federal Biomedical Advanced Research and Development Authority (BARDA) to proceed with advanced development of SOM230. Including a similar BARDA contract for $4.5 million entered into in 2011, the total value awarded is more than $13 million.

Novartis developed the SOM230 to treat hormone disorders known as Cushing’s disease and acromegaly.

The intestine and bone marrow are most susceptible to radiation because of their rapidly proliferating cells.

Treatments exist for irradiated bone marrow but not for the intestine. Radiation damage to the intestine often determines whether a person lives or dies after exposure, Hauer-Jensen said.

“We also have been asked to look at it for prophylactic use by the military, by the Department of Defense,” Hauer-Jensen said.

“BARDA is mainly interested in post-exposure and the military is more interested in the prophylactic administration of the drug.”

He said manuscripts are being prepared for scientific publication based on the findings of the study.

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FOOD ALLERGIES

New Treatments Being Tested

By Katrina Dupins

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or a person allergic to peanuts,

nothing is simple.

Besides not being able to eat peanut products, even exposure to small amounts of peanuts ingested accidentally as a hidden food ingredient could result in a life-threatening allergic reaction.

Stacie Jones, M.D., and her research team at the UAMS-affiliated Arkansas Children’s Hospital Research Institute (ACHRI), are working to protect people who have peanut and other food allergies from experiencing severe allergic reactions.

“The reason we’re so interested in the work we do is that it’s very disconcerting for patients and their families to live in a world where the rest of us just eat whatever we want without having to think so much about it,” Jones said. “To them, their world is filled with potential landmines that can make eating a life-threatening situation.”

Jones is a professor in the Department of Pediatrics and Physiology & Biophysics in the UAMS College of Medicine. She is also section chief of Allergy and Immunology.

Food allergies have been on the rise.

“We know that in the last 20 years, the prevalence of peanut allergies has actually doubled,” Jones said.

Scientists believe the increase could be due to a combination of genetic and environmental factors and diet. There is also a heightened sense of awareness among the general public.

“Our environment has changed. The way we 52

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“

These therapies hold tremendous promise for the future.”

process foods has changed. The way we introduce foods has changed and so have breastfeeding rates.” Jones said. “Genetics have not changed.

That’s the constant. It’s likely many of those factors could impact food allergy prevalence.”

The UAMS food allergy research team is part of a multiinstitutional consortium that has found positive results in the testing of potential new treatment approaches for people with food allergy. The approaches include having participants ingest a food powder, place an allergen extract under the tongue, or wear an allergen patch, all designed to eventually decrease their sensitivity to the allergen.

“These therapies hold tremendous promise for the future,” said Jones. “We’ve really been working to understand the immune system and what is going on with foods in combination with these therapies in the body.”

She said 90 percent of food allergies stem from eight foods: milk, egg, soy, wheat, peanut, tree nut, fish and shellfish. Of those foods, most people do not outgrow their allergies to peanuts, tree nuts, fish and shellfish.

Researchers at ACHRI spend much of their focus on these life-long allergens. In Arkansas, about 30,000 children live with food allergies.

ACHRI researchers have been at the forefront of developing new therapies for those patients.

Many of the studies that use immunotherapies  UNIVERSITY OF ARK ANSAS FOR MEDICAL SCIENCES

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Stacie Jones, M.D. works with a peanut allergy study participant.

have moved from the laboratory into human subjects.

“We have four or five immunotherapies that we can offer in the form of a clinical study,” Jones said. “These therapies often make a big difference in our study participants and their disease. It’s very, very rewarding to see – especially compared to 10-15 years ago when we were just saying ‘Keep avoiding. Trust us. Hopefully you’ll outgrow it.”

“We’ve had enough success with some of the immunotherapies that new companies have been established or are refocusing their work to put immunotherapies into FDA-regulated trials, working toward registration of new products,” Jones said.

Jones hopes the therapies that have been beneficial to the study participants will soon be on the shelf for allergists to use in their clinics. She says it may happen in as quickly as five years.

“There is a lot more attention on food allergy and the impact it has on patients and families.

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And that’s good. Food allergies are not only lifethreatening, but they’re life-changing for both children and adults in their daily lives.”

Jones says she and the other researchers owe much of their advances to the study participants.

“They spend a lot of time, usually many years of their lives on these intense therapies to see if they’re going to have a good outcome or not,” Jones said. “We’ve had an incredible response from people who want to make a difference not only in their own lives but also for future patients.

The really cool thing is that relationships are built and it’s nice to see the science that follows along with that. It’s a great way to come to work every day.

The researchers have high hopes that newer and more impactful therapies are on the horizon.

“We remain excited and focused on making a difference in the lives of our patients and families,” Jones said.

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Meth Addiction

Blocking Meth’s Effects on the Brain

By Susan Van Dusen

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or more than 30 years, Michael Owens, Ph.D., has sought a way for drug addicts to overcome their addiction and return to a drugfree life.

His research began in the 1980s by studying how to treat the overdose of phencyclidine, or PCP. A decade later, he joined forces with UAMS' Brooks Gentry, M.D., and together their research has evolved into a highly specific therapy targeting one of the most addictive illegal drugs: methamphetamine.

“PCP was a very prominent drug for a short time, and we still see a rise in usage occasionally. However, the drug that is really causing problems in Arkansas and worldwide is methamphetamine,” said Owens, professor of pharmacology in the UAMS

College of Medicine.

A highly addicting central nervous system stimulant, meth is primarily produced in clandestine labs, many of which are based in people’s homes, or obtained through drug smuggling operations.

While laws limiting the sale of starter ingredients for meth have greatly reduced production in Arkansas, three surrounding states are in the top 10 nationwide for meth production.

This close proximity to meth hot spots has kept the drug flowing across Arkansas’ state line, where it is responsible for a significant percentage of drug abuse cases.

“Amphetamine abuse accounts for 18.5 percent of patients seeking treatment for substance abuse in Arkansas.

Methamphetamine accounts for the vast majority of these cases,” Owens said.

UNIVERSITY OF ARK ANSAS FOR MEDICAL SCIENCES

The key to success for Owens’ and Gentry’s new therapy is its ability to remain in the bloodstream for weeks at a time.

“It sits, waiting for meth to be introduced into body.

When that happens, it combines rapidly and reduces the rate at which the drug enters the brain, blocking its effects,” Owens said.

If proven effective, it will be the first therapy to reduce meth’s effects for prolonged periods of time, he said.

The results of a phase 1 clinical trial of the medication — named ch-mAb7F9 — were published in the Dec. 15, 2014, issue of the scientific journal mAbs and demonstrated its safety and tolerability in healthy adults.

The next step for Owens, Gentry and their team —  www.uamshealth

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CH3

NH NH

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“

This is the first drug of its kind the FDA has ever seen.”

including collaborators Misty Stevens, Ph.D., and Melinda Gunnell — is to focus on additional safety testing for people with meth addiction.

Because this is a new type of therapy, extra time to determine its safety is an essential part of the development process.

“This is the first drug of its kind the FDA has ever seen.

They are very supportive, but also are very cautious,” said Gentry, professor and chairman of the UAMS Department of Anesthesiology.

A grant of $5 million from the National Institutes of Health (NIH) National Institute on Drug Abuse (NIDA) will support production of the monoclonal antibody and fund more safety testing to prepare the team to conduct a phase 2 clinical trial involving meth users, which they hope to begin in about three years.

NIDA has provided the team continual support since the mid-1990s, and even longer for Owens’ early-stage research.

In addition to their work on the monoclonal antibody, the team announced a $9.55 million NIDA grant in early 2015 to continue its study of an antibody vaccine for meth addiction, which would allow the body to develop immunity UNIVERSITY OF ARK ANSAS FOR MEDICAL SCIENCES

to the drug’s effects.

“While the monoclonal antibody has an immediate effect, the vaccine could take up to six weeks to generate a response. This could be helpful for someone who isn’t a hardcore user, but still needs help quitting,” Gentry said.

Like the monoclonal antibody, the vaccine wouldn’t interact with other medications, nor would it impact brain function or interfere with psychiatric counseling. The vaccine also would carry a lower price tag than the monoclonal antibody and could last up to nine months in the body.

Assuming the antibody and vaccine receive federal Food and Drug Administration approval, they can be provided as an integral part of a meth user’s complete treatment program, which consists of counseling and possibly other medications to reduce craving.

While Owens and Gentry are clear they aren’t developing a cure for meth addiction, they do see their discoveries opening a door for addicts who are ready to quit.

“The antibody is for people who want help and are willing to change their behavior. It gives you a chance to recover and outlive your disease,” Owens said. www.uamshealth

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LUNG CANCER

“

The bottom line is what we’re doing is going to benefit the population of Arkansas.”

Public Health Tackles Lung Cancer

By Spencer Watson

Mohammed Orloff, Ph.D.

M

ohammed Orloff, Ph.D., is hoping to figure why, despite the proven link between cigarette smoking and lung cancer, some smokers never develop the disease and some non-smokers do. By extension, the hope is to shed light on why anyone develops the disease.

To further that understanding of the causes of lung cancer, Orloff is studying the genetics of individuals and specific populations, including those in Arkansas. He believes that genetic alterations and environmental factors together contribute to the development of lung cancer.

The genetic variation in the Arkansas population, like any population, may have been influenced by a unique demographic history, environment and other forces.

“I think the bottom line is, what we’re doing is going to benefit the population of

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Arkansas,” Orloff said.

While research has already identified certain mutations that can lead to lung cancer, issues still persist in early detection, design of effective treatments and understanding the cause.

Orloff ultimately hopes to identify biomarkers that will improve detection rates and reduce screening costs as well as figure out how environmental factors such as smoking interact with genes to make a disease more aggressive.

So far, his research has uncovered nine candidate genes, two of which are being tested and screened for mutations that may play into the development of the cancer.

“We used to think in terms of a single candidate gene here or there in the human genome,” Orloff said. “Now we have multiple players, genetic and non-genetic. It’s not just one gene and one gene alone.”

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BIOMEDICAL INFORMATICS

Using Data to Improve Health Care

By Ben Boulden

Charlotte Hobbs, M.D., Ph.D.

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ne of the most valuable assets of academic health science centers is clinical data generated every time a patient receives care.

This has spawned a relatively new discipline called biomedical informatics, which takes large amounts of health care data and uses it to make improvements in health care.

With forward thinking,

Charlotte Hobbs, M.D., Ph.D., executive associate dean for research in the College of Medicine, is leading the group working to develop the use of biomedical informatics.

The group is implementing methods that help researchers pull information from the Enterprise Data Warehouse, an ever-expanding data repository of more than 1 million de-identified inpatient, outpatient, lab and registrations records of patients.

As an epidemiologist, pediatrician and research scientist, Hobbs has experience using large databases of medical information to study population health as well as working with patient registries and electronic health records as part of integrated research in 2010, UAMS leadership programs and biorepositories. charged UAMS Biomedical By improving ways Informatics and Information clinicians and scientists use the Technology staff and faculty Enterprise Data Warehouse, with building an Enterprise Hobbs hopes that physicians Data Warehouse. will be able to improve patient In 2014, the Enterprise Data care while improving the Warehouse underwent a major efficiency with which that care reorganization to enhance the is delivered and even reduce utility of UAMS clinical data health care costs by eliminating to improve clinical operations redundant and unnecessary and research projects. tests.

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Permit No. 1973 Little Rock, AR

4301 W. Markham St., #890 Little Rock, AR 72205

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bout the

University of Arkansas for Medical Sciences Arkansas’ only comprehensive academic health sciences center

COLLEGES of Medicine, Nursing, Pharmacy, Health Professions and Public Health; and a Graduate School A state-of-the-art hospital A statewide network of regional centers Advanced telehealth and telemedicine programs Research funding of $108.72 million across UAMS and UAMS researchers working in affiliated institutions.

Seven Institutes: Winthrop P. Rockefeller Cancer Institute, Jackson T. Stephens Spine & Neurosciences Institute, Myeloma Institute, Harvey & Bernice Jones Eye Institute, Psychiatric Research Institute, Donald W. Reynolds Institute on Aging and Translational Research Institute.

Private support is essential to our mission to engage in activities that result in better health. Please consider making a tax-deductible gift today by calling us at (501) 686-8200 or giving online at uamshealth.com/giving. All gifts are important and greatly appreciated.

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