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Monthly Archives: May 2014

New Investigators Gain Footing With KL2 Awards

TRI’s KL2 Career Development Award recipients from 2009-2013 are (seated l-r) Andrew James and Keneshia Bryant; (standing) Ling Gao, Elvin Price, Anthony Goudie, Joshua Kennedy, Dennis Kuo and Tiffany Haynes. Not pictured, Holly Felix, Brooke Montgomery, and Karen McNiece Redwine.

When UAMS received the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) in 2009, leadership moved quickly to invest in promising new researchers.

With the idea of “growing our own” researchers, the UAMS Translational Research Institute (TRI) has offered annual KL2 Career Development Awards, which provide salary support, research funds, and mentored training to junior investigators. Below are brief updates of the research being conducted by TRI’s KL2 recipients:

2009
Holly Felix, Ph.D., M.P.A.
In addition to studying the impact of obesity in long-term care, Holly Felix is getting traction with her evaluation of the Community Connector Program that links Medicaid-eligible, physically disabled adults and the elderly to long-term care services. Her KL2 helped her disseminate earlier findings that the Community Connector Program could save Arkansas’ Medicaid system $2.6 million over three years. Funded by NIH, Felix is studying the program in 15 counties after Medicaid expanded it from three. She is currently pursuing NIH funding to expand her study of obesity in long-term care.

2010
Dennis Kuo, M.D., M.H.S.
Having set out to solve the complex care needs of patients at Arkansas Children’s Hospital (ACH), Dennis Kuo is thinking big: “You have to redesign the health care system,” he said. Now the principal investigator on two federally funded studies, his data-driven work is helping achieve better understanding of patients’ health needs, family needs, and their health care use patterns. As a result, ACH is developing personal care teams, especially for those with special health care needs, and Kuo was recently tapped to lead the rollout of ACH’s Patient-Centered Medical Home program.

2011
Keneshia Bryant, Ph.D., R.N., F.N.P.-B.C.
Motivated by the patients she saw as a family nurse practitioner, Keneshia Bryant has used her KL2 to better understand the roles of ethnicity, culture and gender on depression. Her research is focused on addressing longstanding mental health barriers in rural African-American communities, including service infrastructure and stigma. She is pursing funding for a faith-based stress management intervention that she developed with the community. Bryant is also co-principal investigator of a federally funded, community-based approach to reducing health disparities and co-investigator on two other mental health studies.

Ling Gao, M.D., Ph.D.
Every Sunday, Ling Gao checks in by phone with her late-stage Merkel cell carcinoma patients. When the dermatologist and researcher recently discussed specific cases, she fought back tears, underscoring her resolve to find treatments for the rare, aggressive skin cancer. With no commercially available cell lines and limited resources, she has personally managed the challenging, daily pursuit of growing cells in her lab. Her reward is now within sight. Using tumor cells derived from her patients, she has identified potential therapeutic targets and will seek to publish her findings this year.

Andrew James, Ph.D.
Using a functional MRI, Andrew James has analyzed the brains of 53 healthy adults, providing a suitable sample size for mapping brain function. The results are most striking in the different ways that healthy people use their brains to accomplish the same mental tasks. His results are being applied to better understand cognitive deficits in a broad range of psychiatric and neurologic illnesses. This foundation is essential to his epilepsy research and has led to new collaborations. He hopes that functional MRIs will one day inform medical decision-making.

Karen McNiece Redwine, M.D., M.P.H.
Searching for ways to more effectively treat children with hypertension – one of the most prevalent chronic diseases in America with significant early morbidity – Karen McNiece Redwine used her KL2 to study the potential benefits of ambulatory blood pressure monitoring. She found that multiple blood pressure readings taken in patients’ natural environments over an extended period resulted in changes to patients’ medication regimen about 40 percent of the time. She presented the findings earlier this month at the Pediatric Academic Society in Vancouver.

2012
Anthony Goudie, Ph.D.
Using national hospital databases, Anthony Goudie is searching for ways to improve hospital quality of care. His KL2 effort is focused on understanding the variation in rates of pediatric hospital-acquired infections such as Clostridium difficile. The challenge of producing apples-to-apples hospital comparisons prompted Goudie to develop a novel risk-adjustment algorithm that has been well received in his field. He has also identified common traits associated with hospitals with low infection rates. He hopes his findings will be used to develop fair incentives to help other pediatric hospitals improve their quality of care.

Tiffany Haynes, Ph.D.
To address mental health disparities in underserved, rural African-Americans, Tiffany Haynes reached out to the strength of the community: Churches. Haynes, a clinical psychologist, has gathered qualitative data from church leaders, other members of the faith community and rural African-Americans to design interventions in which churches can play a key role in decreasing disparities. Haynes is also co-investigator on a Patient Centered Outcomes Research Institute (PCORI) grant that is addressing barriers to mental health care in underserved African-American communities.

Brooke EE Montgomery, Ph.D., M.P.H.
While working on an earlier project, Brooke Montgomery, a behavioral scientist, was moved as female survivors of emotional, sexual, and physical violence discussed their subsequent struggles to find safe, healthy relationships with men. Motivated by their stories, she has partner with shelters, treatment facilities, and advocacy and policy groups to design a sexual health intervention program. She is now recruiting women participants who have survived violence, trauma and abuse. Montgomery is also studying how violence against women may impact HIV risk behaviors as part of the national HIV Prevention Trials Network Scholars Program.

2013
Joshua Kennedy, M.D.
As a new KL2 scholar, Joshua Kennedy, an allergy and immunology specialist, is excited to be part of an asthma research team that is conceiving innovative research techniques on a national scale. Using donated living lungs, Kennedy has presented preliminary findings that the airways of asthmatics react differently and perhaps more severely to the common cold than nonasthmatics. He and the team are now trying to tease out the cause of this sometimes fatal phenomenon. Human studies will come next, and Kennedy hopes their work will lead to treatment breakthroughs.

Elvin Price, Pharm.D., Ph.D.
By targeting certain nuclear receptor genes, Elvin Price hopes to someday ensure that individual patients get the safest, most effective medicines for their particular condition. His KL2 has allowed him to focus on genetic associations with blood pressure, lipid and glucose levels. He has identified genes of interest in the lab and then analyzed them in patients. Having completed his first set of analyses of clinical data, Price is seeking to replicate the results in collaboration with the University of Michigan. He is also pursuing studies of treatment-related outcomes over time.

View a chart of the KL2 recipients’ number of publications and grants since their awards.

Editors Note: Sundararaman Swaminathan, M.D., a 2010 recipient, is continuing his diabetes-related research at the University of Virginia, and Wang “Steve” Cheung, M.D., Ph.D., a 2009 recipient, is in private practice in Orlando, Fla.

Funding Opportunities

This list of funding opportunities was updated on May 15 and includes a tab with archived funding opportunities that remain open. It is compiled and updated every two weeks by the Division of Pharmaceutical Evaluation and Policy in the College of Pharmacy.

Terabytes of Secure Space Available for Research

UAMS IT has 5.7 terabytes of space available to faculty and staff who need data storage for research-related materials. The space is available at no charge and provides security and data protection with daily automated backup. It is available for MS Office or similar (text, etc.), Adobe files, SPSS or SAS files, images, database files and others.

To make your request, use the self-service website http://itss.uams.edu, or email TechSupportCenter@uams.edu.

Read more here about how to make your request.

TRI-Supported Researcher’s HPV Vaccine Shows Promise in Early Trial

May 12, 2014 | A potential breakthrough HPV (human papillomavirus) vaccine for women who already have HPV appears to have passed its first major test for Mayumi Nakagawa, M.D., Ph.D., at the University of Arkansas for Medical Sciences (UAMS).

The unpublished results of an ongoing Phase I clinical trial are showing “a promising clinical response” to the vaccine and indicate that it is safe, said Nakagawa, associate professor of pathology in the UAMS College of Medicine.

HPV vaccines on the market today are used for preventing HPV only in women who have never had the virus. There is no vaccine for women already infected with HPV.

Nakagawa’s research is funded by a five-year grant from the National Institutes of Health (NIH). She has also received pilot funding and other support from the UAMS Translational Research Institute, which is a recipient of a NIH National Center for Advancing Translational Sciences (NCATS) Clinical and Translational Sciences Award (CTSA).

Nakagawa will present the results of the first two doses involving 12 women at the 29th International Papillomavirus Conference in August. Recruitment of research participants will continue through 2014, and the Phase I study will conclude in 2015. Preparations toward the Phase II trial are under way, and will mainly examine the vaccine’s effectiveness.

HPV, a sexually transmitted virus, is associated primarily with cervical cancer, the fourth-most common cancer in women worldwide. Cervical cancer is almost always caused by HPV, which also causes anal, oropharyngeal, penile, vaginal and vulvar cancers. It is estimated to be responsible for 5.2 percent of cancer cases in the world.

Nakagawa’s vaccine could benefit women with existing infections and precancerous lesions, and new research indicates that it could significantly reduce the incidence of preterm births. It would do so by giving women an alternative to surgical treatment for HPV-related precancerous lesions such as high-grade squamous epithelial lesions (HSIL). Surgery, Nakagawa notes, was recently found to have the unintended side effect of increasing the incidence of preterm delivery, from 4.4 to 8.9 percent. Therefore, for women who still plan to have children, a therapeutic vaccine such as the one being developed by Nakagawa’s group is likely to become the first line of therapy when it is approved by the Food and Drug Administration (FDA).

The vaccine is the culmination of 20 years of research for Nakagawa. HPV has two cancer-causing proteins, and her group found that women who can mount immune responses to one of them called E6 had a much better outcome. Her biggest break came while studying wart treatments, when she learned that a naturally occurring yeast in the body, Candida, had an anti-HPV effect.

Nakagawa’s vaccine, which consists of synthetically made E6 and Candida, would also benefit women in developing regions of the world where surgical expertise may not be available.

“It’s very exciting because it will extend the number of women who can be helped, especially those in low resource areas where HPV disease burden is greatest,” she said.

TRI Pilot Award, Discovery Help UAMS Researcher Land $1.83 Million NCI Grant

A surprise discovery that could lead to new treatments for herpes viruses that infect more than 90 percent of the world’s adult population has led to a $1.8 million grant to the University of Arkansas for Medical Sciences (UAMS) from the National Cancer Institute (NCI) at the National Institutes of Health (NIH).

UAMS researcher Craig Forrest, Ph.D., found that a certain protein may suppress the herpes virus and possibly several cancers that are caused by related herpes viruses.

“This protein really appears to put the brakes on the virus from the start,” said Forrest, an assistant professor in the UAMS College of Medicine’s Department of Microbiology and Immunology.

Forrest’s early research was funded by the Arkansas Biosciences Institute, supported by Arkansas’ share of a national tobacco industry settlement, and the NIH-funded Center of Biomedical Research Excellence (COBRE) at UAMS, and a pilot study funded by the UAMS Translational Research Institute.

“We got some very unique data from the pilot study that led us to test the function of p53 in chronic herpes virus infection,” Forrest said. “We found that the p53 protein is restricting the virus from establishing a chronic infection. If you deleted p53 from the mouse genome, you got a really big increase in the number of infected cells.”

The five-year NCI grant will allow Forrest and collaborating researchers to use innovative genetics techniques to manipulate the herpes virus and its genes as they test the protein (p53), which is known for suppressing cancer.

He hopes that a more complete understanding of the protein’s role in restricting the virus will someday lead to new treatments. While most people have a natural resistance to cancers caused by the herpes virus, treatments could be lifesaving for those with weakened immune systems, including organ transplant patients, HIV/AIDS patients, and cancer patients undergoing chemotherapy.

“For people who have compromised immune systems, herpes viruses like the Epstein-Barr virus have a nasty habit of coming back as different diseases like lymphoma and other cancers,” Forrest said.

The Epstein-Barr virus, which is in the family of herpes viruses that Forrest is studying, infects more than 90 percent of the adult population, but most people will never develop a cancer caused by the virus.

“We have a technique by which we can allow the virus to set up shop and then knock out viral genes,” he said. “We propose doing the same thing with the p53 protein. We can delete p53 and then ask what happens in terms of the chronic viral infection: Do you increase or decrease viral loads? Do you increase cancer incidence? We predict that you would, but we don’t know for sure.”

Forrest, a Jonesboro native, joined UAMS in 2009 after completing postdoctoral research at Emory University in Atlanta. His discovery of the important role of the p53 protein was made while testing various signaling proteins in the genomes of mice.

Forrest’s grant application to the NCI earned a rare perfect score of 10 from reviewers, who anticipate that his research “may reveal novel therapeutic targets,” and concluded, “In sum, there is considerable enthusiasm for the talented new investigator (Forrest) and the proposed work ….”

“It was exciting to see the reviewers’ scores, and much of the credit goes to some key collaborating researchers at UAMS and my hard-working lab group,” Forrest said. “They are directly responsible for the preliminary data that made the grant successful.”

TRI, UAF Announce Telehealth Pilot Program

TRI and the University of Arkansas, Fayetteville on Wednesday announced they are offering telehealth research pilot grants of up to $15,000, with an additional $5,000 for projects that include a UAF collaborator. For more information and to download the Request for Applications (RFA):

Download RFA.

TRI Issues Pilot Award Request for Applications

The Translational Research Institute (TRI) today issued a request for applications for its 2014 pilot awards program. Awards are $50,000 maximum and have a 1-year time limit. The letter of intent is due June 2, and full applications are due Aug. 4, 2014. New this year is a requirement for a letter of approval from the IRB or IACUC with the full application. Learn more here.

Contact: Kelly Bulloch, kwbulloch@uams.edu, 501.686.5417.

MacMillan-Crow Named Director of TRI Pilot Program

Lee Ann MacMillan-Crow, Ph.D., a professor in the Department of Pharmacology/Toxicology, has been named director of TRI’s Novel Methodologies and Pilot Studies Program.

As director, MacMillan-Crow will play a key role in the promotion of translational research through the administration of TRI’s annual pilot funding program. TRI funds translational research at all levels, from basic science to clinical trials of new therapeutics, and community-based interventions. The program has awarded $3.6 million to UAMS researchers over the last five years.

MacMillan-Crow is program director of the Interdisciplinary Toxicology PhD Program and a standing member on the Surgery, Anesthesiology, and Trauma Study Section at NIH. Her laboratory has been funded by the NIH since 2001 and has a long-term interest in oxidant generation and mitochondrial damage during renal ischemia/reperfusion, as it relates to transplantation injury.

In addition, her research is examining the therapeutic potential of several agents to block renal mitochondrial injury during warm and cold ischemia, using rat, porcine, and a human model of transplantation. This research has led to a Use Patent and pending Phase II Small Business Grant from NIH. Another recent area of study in collaboration with Philip Mayeux, Ph.D., supported by an NIH RO1 grant, is related to the role that mitochondrial superoxide has on mitochondrial and renal damage during sepsis.

MacMillan-Crow earned her doctorate from the University of Alabama at Birmingham in 1994 and moved to UAMS in 2003. She has served as primary mentor to 10 graduate students and served on 18 dissertation committees.