Oct. 15, 2015 | Identifying a patient’s genetic mutation led University of Arkansas for Medical Sciences (UAMS) physician-researcher Ling Gao, M.D., Ph.D., to an existing drug that eliminated the patient’s stage IV Merkel-cell carcinoma. Gao’s findings, made in collaboration with two other UAMS researchers, were published today in The New England Journal of Medicine.

Gao is a recipient of the UAMS Translational Research Institute’s (TRI) KL2 Mentored Research Career Development Scholar Award, which provided two years of research funding and translational research training.

Metastatic Merkel-cell carcinoma is often fatal and there is no effective treatment. Gao’s 86-year-old female patient was diagnosed in 2013 with stage IIIB Merkel-cell carcinoma of the right temple. She had surgery and received radiation therapy in May 2013 and additional surgery in July 2014. In November 2014, doctors confirmed that the cancer had metastasized.

Gao, a dermatologist who treats Merkel-cell carcinoma patients from Arkansas and surrounding states, performed genetics tests on the tumor that revealed multiple mutations, including PI3Kδ.

Gao was aware that the drug idelalisib is a novel PI3K pathway inhibitor approved by the Food and Drug Administration (FDA) for treatment of B-cell lymphoma, a cancer of the blood. She was also aware of recent studies showing that disruption of the PI3Kδ mutation allows the body to mount an effective antitumor immune response.

On the basis of her laboratory work and knowledge of idelalisb, Gao began treatment of the patient with the drug on Feb. 6, 2015.

Three months after administering the idelalisib, there was no sign of the tumor in the patient’s liver, Gao said. Her findings were published in the Journal in a letter to the editor.

Based on what she’s learned, Gao said the case can be made for further study of PI3Kδ inhibitors like idelalisib in solid tumors, not just blood cancers.

“The efficacy of idelalisib in our patient provides initial clinical evidence that the targeting of PI3Kδ in Merkel-cell carcinoma is warranted,” Gao said in the letter, which  was also signed by UAMS’ Fade Mahmoud, M.D., and Mallory B. Shiver, M.D.

Gao also credits support she received from Peter Emanuel, M.D., director of the UAMS Winthrop P. Rockefeller Cancer Institute, and James Suen, M.D., chair of the Department of Otolaryngology-Head and Neck Surgery in the UAMS College of Medicine.

View the article and accompanying PET-CT findings here.

Gao’s research has been supported by the UAMS Translational Research Institute through the National Institutes of Health National Center for Advancing Translational Sciences, the Department of Dermatology in the UAMS College of Medicine, UAMS Winthrop P. Rockefeller Cancer Institute, and the Arkansas Biosciences Institute.

UAMS’ Aliza Brown, Ph.D., recently received a nearly $200,000 Genentech stroke research award after she incorporated ideas in her application from the first TRI Research Forum in June 2014.

The grant was one of only three community stroke pilots funded by Genentech in the United States. The study will enable Brown to determine paramedics’ recognition of stroke and whether stroke patients are being taken to stroke-ready hospitals.  In addition, she is developing an educational video for paramedics in partnership with the UAMS-led Arkansas SAVES (Stroke Assistance through Virtual Emergency Support) telestroke program and the Arkansas Department of Health’s Arkansas Stroke Registry.

Her hope is that the study will provide data to support state sanctioned stroke guidelines and practices for emergency medical services.

“The Department of Health is very interested in this project because this will help promote legislation for the stroke guidelines and to create a stroke dashboard to guide EMS agencies to the appropriate hospitals,” Brown said.

Brown, an assistant professor of radiology, joked that she was TRI’s first Research Forum “guinea pig.” The forums include established researchers and biostatisticians who provide feedback on investigators’ grant applications.

“The forum panel was excited about the application and said it was very translational,” Brown said. “They gave me some great advice. I learned a lot and I got a pretty good grant out of it.”

A key recommendation came from Jean McSweeney, Ph.D., R.N., professor and interim dean of the College of Nursing. “Dr. McSweeney suggested that the study include utilization of the Simulation Center and an educational intervention, so I did that,” Brown said.

Her study will validate the educational intervention – a training video – by measuring Pulaski County paramedics’ stroke recognition rates following training. Garland County EMS will serve as the control, where EMS workers will not receive the training video and whose stroke recognition rates will be followed concurrently.

“I hope that this study can provide data the state needs to make these stroke guidelines a reality,” Brown said.

To date, TRI has hosted nine Research Forums. To request a forum, email TRIservices@uams.edu.

Submitted on Sept. 25, TRI’s 1,263-page renewal application for a Clinical and Translational Science Award (CTSA) was made possible thanks to the dedication of faculty and staff across UAMS and its affiliated institutions, said TRI Director Laura James, M.D.

“Faculty reviewers and writers from across all colleges tackled this project in a spirit of teamwork that allowed us to develop the strongest possible application,” James said. “This was a cross-college, cross-department, cross-institution effort that involved basic scientists, clinical researchers, community engagement researchers, etc.”

Reviewers were Larry Cornett, Ph.D., Charlotte Hobbs, M.D., Ph.D., Donald Mock, M.D. Ph.D., Mike Owens, Ph.D., Paula Roberson, Ph.D., and Nancy Rusch, Ph.D. This group’s work included nine two-hour meetings. Other major contributors to the review group were DeAnn Hubberd and Peggy Brenner from the UAMS Office of Grants and Scientific Publications (OGSP).

Meanwhile, Mary Aitken, M.D., Pedro Delgado, M.D., and Rusch spent countless hours writing the application’s two training components, James said.

Other primary writers were Beatrice Boateng, Ph.D., Barry Brady, Mathias Brochhausen, Ph.D., Cornett, Geoff Curran, Ph.D., Gloria Richard-Davis, M.D., Ellen Fischer, Ph.D., Kristie Hadden, Ph.D., Hobbs, Laura Hutchins, M.D., Greg Kearns, Pharm.D., Ph.D., Brad Martin, Pharm.D., Ph.D., Pearl McElfish, Ph.D., Jean McSweeney, Ph.D., R.N., Mock, Pope L. Moseley, M.D., Alison Oliveto, Ph.D., Owens, Tamara Perry, M.D., Fred Prior, Ph.D., James Raczynski, Ph.D., Paula Roberson, Ph.D., Kate Stewart, M.D., M.P.H., Dennis Sullivan, M.D., Billy Thomas, M.D., and Pam Williams, Ph.D.

Valuable expertise was contributed by Hari Eswaran, Ph.D., as well as Barry Brady and Phaedra Yount from the Arkansas Children’s Research Institute (ACRI), and OGSP staff. TRI’s staff was critical to the process, James said, including Pamela Christie, Amy Jo Jenkins, Donna Mattingly, Anthony McGuire, and Laura Wilson, and many others who provided information for the grant.

If the application is successful, UAMS will receive about $24.4 million over five years. The CTSA Award is funded by the National Institutes of Health (NIH) National Center for Advancing Translational Sciences (NCATS).

While the launch of the Integrated Clinical Enterprise is a focus point for UAMS this year, Dean Pope L. Moseley, M.D., assured faculty researchers at a Sept. 15 Town Hall meeting that a key objective of the service lines, and his top priority, is strengthening research and education programs.

“My goal is to make us better as an academic enterprise,” said Moseley, who is internationally known for his laboratory research in cellular adaptations to exercise and his expertise in biomedical informatics. He became dean in July after chairing the Department of Internal Medicine at the University of New Mexico School of Medicine for 14 years.

The forum, co-hosted by pediatrics Professor and Executive Associate Dean for Research Charlotte Hobbs, M.D., Ph.D., was well received by faculty members.

Stavros Manolagas, M.D., Ph.D., lauded Moseley’s arrival and strong support for the research enterprise as well as the commitment of UAMS leaders to support research with greater funding resources that are anticipated to be generated through the new clinical service lines.

“This is the most exciting news, I believe, at this institution in the 20 years that I have been here,” said Manolagas, a distinguished professor and director of the Division of Endocrinology and the internationally recognized UAMS Center for Osteoporosis and Metabolic Bone Diseases. “I want to wish you the best of luck,” he said, drawing a round of applause for Moseley.

Moseley noted that research and education are not self-supporting and that clinical revenue is by far the largest funding source for UAMS. “Research and education need fuel from the clinical engine,” he said.

An institution could hypothetically optimize the clinical delivery system at the expense of everything else, Moseley said.

“But that’s not who we are,” he said. “We didn’t come here to be a multi-specialty practice group. We came here to be a community of scholars. We are here to develop new knowledge and to train the next generation of scientists and clinicians.”

Moseley said he came to UAMS because he was impressed that an academic medical center had “the will” to completely change the clinical delivery model and system for managing the flow of its revenue in an effort to improve patient care while also generating new revenue for strategically planned research and education initiatives. “What we are all trying to do is to find that balance point,” he said.

Moseley outlined priorities for enhancing the research environment, including working with chairs to recruit outstanding researchers at all levels and in key areas that support research. He cited the recent recruitment of Fred Prior, Ph.D., from Washington University in St. Louis as the inaugural chair of the Department of Biomedical Informatics.

He said the college will work to support successful, established research programs and develop a systematic, central approach to bridge funding for successful investigators who experience lapses in extramural funding. Additionally, Moseley said he will work with research leaders to “lower the activation energy” required for successful research by addressing any barriers in areas such as human subject and animal care review.

Emphasizing the importance of chairs in determining how funds are allocated for research, he said a research-focused strategic retreat is being planned. Investigators can have input in the process through their chairs, he added.

An immediate priority is obtaining renewal of the Clinical and Translational Science Award (CTSA) from the National Institutes of Health National Center for Advancing Translational Sciences, which Moseley said is a “defining grant of an academic medical center.”

The UAMS Translational Research Institute (TRI), under the leadership of pediatrics Professor and TRI Director Laura James, M.D., has been preparing the CTSA renewal application to meet the Sept. 25 deadline. Moseley urged faculty members to support the final efforts that were underway.

Longer-range major institutional initiatives include building the biomedical informatics program under Prior’s leadership and preparing the Winthrop P. Rockefeller Cancer Institute’s application for National Cancer Institute designation in a couple of years, Moseley said.

The majority of the meeting was devoted to questions and comments about research priorities and needs. Recommendations from faculty members included developing an inpatient clinical research unit, improving access to research core services, and working more closely with the Central Arkansas Veterans Healthcare System (CAVHS) and leveraging VA grant opportunities for both basic and clinical researchers.

“Compared to other institutions that have VA facilities next door, we tend to underutilize their Career Development Program and the VA Merit Review Program,” said Curt Hagedorn, M.D., a Professor in the Division of Gastroenterology and Hepatology who serves as vice chair for VA Affairs in the Department of Internal Medicine and chief of Medicine at CAVHS.

Michael Jennings, Ph.D., professor and chair of the Department of Physiology and Biophysics and executive associate dean for Basic Sciences, said there is a misconception that VA awards aren’t available for basic scientists and lack of understanding about how to get into the VA system. “But this is something we can really take advantage of,” he said.

Moseley and faculty members spoke about the importance of growing the numbers of physician-scientists through recruitment, mentoring, training programs and other means.

John Arthur, M.D., Ph.D., director of the Division of Nephrology, used a football analogy in advocating for maximizing training grant opportunities, such as the NIH’s career development K awards.

“If you really want, over the long term, to have a team that can compete for the SEC championship year after year, you really have to grow it from the bottom up,” Arthur said.

The meeting opened with a presentation by Hobbs on new services for researchers, including improvements to the COM research website and the UAMS Grant Repository, which will provide junior faculty researchers with examples of submitted grant applications as a training resource to help them to improve their applications and chance of funding.

Hobbs showed a graph reflecting the downturn in NIH funding over the past five years. “We are really focused on turning that around,” she said.

Moseley also referred to the downturn in his remarks. “That is behind us,” he said. “It is our job to change course, and I am excited because we are going to do that.”

For more of Moseley’s thoughts on the importance of research and the academic mission, read his Executive Blog posts on the Inside UAMS intranet.

Learn More:

For information about eligibility and applying for VA grants, contact Sue Theus, Ph.D., deputy associate chief of staff/research, CAVHS, at (501) 257-4841 or Sue.theus@VA.gov.

Editor’s note: A version of this article also appears in the September COMmunication newsletter.

Discover Your Next Collaborator With UAMS Profiles

Finding collaborators doesn’t have to be a scavenger hunt. UAMS Profiles, a new online research networking tool, eliminates the mystery and the miles separating researchers from potential collaborators.

Created at Harvard University, Profiles was obtained and customized for use at UAMS by the Translational Research Institute (TRI), the Winthrop P. Rockefeller Cancer Institute and the Department of Biomedical Informatics. Through its service to researchers, UAMS Profiles delivers on a key team science objective of the NIH National Center for Advancing Translational Sciences (NCATS), which oversees 62 Clinical and Translational Science Award (CTSA) institutions across the United States, including TRI.

Profiles (TRI.uams.edu/Profiles) combines a key-word directory with illuminating interactive visualizations that show each faculty member’s collaborations or networks with other researchers, and it shows how those networks have evolved over time.

UAMS faculty information is currently shared within the UAMS network and may be viewed by Profiles members at the main UAMS campus, Arkansas Children’s Hospital and its Research Institute (ACRI), the UAMS Northwest Arkansas campus, and by faculty at the Central Arkansas Veterans Healthcare System. In 2016, UAMS Profiles will be linked nationally with other research institutions that use Profiles or similar networking programs.

Profiles accounts were automatically established for all UAMS faculty with information imported from UAMS FacFacts (Faculty Facts), TRACKS and PubMed. Each faculty member’s Profile Page includes biographical information, contact information and their researcher networks. A researcher’s network may be viewed on the website as:

You’ll want to check out the September TRIbune, which features UAMS Profiles, the exciting new platform for finding collaborators.  This issue also highlights a TRI-supported stroke researcher who received a Genentech grant, as well as TRI-cited publications by your colleagues.

Download PDF | View Newsletter Archive

UAMS’ 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 (TRI), 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 Sciences (NCATS) Clinical and Translational Science Awards (CTSA).

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

This article originally appeared in the UAMS Journal magazine.