Newswise — BIRMINGHAM, Ala. – The National Institutes of Health has awarded the University of Alabama at Birmingham Center for Clinical and Translational Science $33.59 million over four years to continue the center’s programs advancing translational research.

Since its initial funding in 2008 through Alabama’s only Center for Translational Science Award to work toward innovative discoveries for better health, the UAB CCTS has nurtured UAB research, accelerating the process of translating laboratory discoveries into treatments for patients, training a new generation of clinical and translational researchers, and engaging communities in clinical research efforts.

The CCTS will continue to advance its mission to accelerate the delivery of new drugs, methodologies and practices to patients at UAB and throughout a partner network of 11 institutions in the Southeast.

“We are excited by the capacity to continue to enhance our institution’s and our region’s innovative research and medical care,” said Robert Kimberly, M.D., UAB CCTS director. “Through internal and external partnerships, as well as a robust clinical environment and cutting-edge informatics and clinical trial resources, we look forward to working with our patients over the course of their lifespan.”

Congress launched the CTSA program in 2006, which is overseen by the National Center for Advancing Translational Sciences.

The amount of this award, more than double its previous funding awarded in 2008 and one of the largest at UAB, reflects an unmatched enthusiasm for the CCTS and its affiliated programs. It includes funding for 10 annual pre-doctoral training awards, 10 summer training awards, and eight career development awards for senior postdoctoral fellows or faculty-level candidates.

“Our training programs continue to foster a culture of responsible, ethical practice among students, faculty and clinicians conducting human subjects research,” Kimberly said. “The NIH’s support of our expansive partner network, encompassing 11 regional academic and medical institutions throughout Alabama, Louisiana and Mississippi, will allow us to further grow our scope of practices and research resources as we look to tackle health disparities in the Southeast.”

Through One Great Community, the CCTS’ community engagement enterprise, and the Community Health Innovation Awards, the CCTS engages Greater Birmingham­­-area residents in innovative programs designed by community members to improve their neighborhoods.

“UAB is fully committed to the goals of the CCTS and to its continued development as a hub for clinical and translational research in the Southeast,” said UAB President Ray L. Watts. “This significant renewal speaks to the tremendous work and vision of our CCTS leadership and team, as well as our clinical infrastructure, scientific strengths, informatics expertise, training programs, and biostatistical and research design assistance.

“The CCTS touches researchers in all UAB schools and across the partner network, and we are thrilled that this important work will continue with the confidence and support of the NIH.”

State and Regional Impact“The growth of the Center for Clinical and Translational Science at UAB will foster economic development in the state and throughout the region,” said Senator Richard Shelby. “With a history of providing optimal clinical care and innovation in human health, UAB’s receipt of this prestigious award enables the continued development of the workforce that is necessary to meet the needs of future research advancement.”

Alabama Governor Robert Bentley, himself a physician, voiced his appreciation for the CCTS’ initiatives. “The center has been highly effective in providing assistance in the state’s efforts to eliminate the health disparities seen throughout our region,” Bentley said. “Whether across the life course or in underserved groups disproportionately affected by cancer, stroke, heart conditions and other diseases prevalent in our state, the center has been exemplary in reaching out to our citizens.”

UAB Vice President, Research and Economic Development Richard Marchase, Ph.D., says he is particularly pleased that the CCTS is building on UAB’s history of serving populations burdened by health disparities through its partnerships with other state and regional institutions committed to advancing health through translational research. “It is through this culture of commitment and collaboration,” he said, “that we have become a national leader in biomedical research.”

CCTS specializes in turning ideas into action

In 2006, Congress launched the Center for Translational Science Award (CTSA) program to help accelerate the rate at which research discoveries are transformed into practical applications.

The barriers are numerous: Sometimes it’s a lack of funds to pursue a promising hunch, or access to adequately trained staff to make a clinical trial possible — or simply the absence of an experienced mentor to show an investigator how to take the next step.

Since 2008, UAB’s Center for Clinical and Translational Science (CCTS) has been filling each of these roles and more in Birmingham and beyond. The NIH recently awarded the CCTS nearly $34 million to continue and expand its wide range of programs.

“The CCTS pools key resources to allow our researchers to more efficiently design and conduct their studies,” said Robert P. Kimberly, M.D., director of the CCTS and associate dean for Clinical and Translational Research in the UAB School of Medicine.

“We also provide training opportunities to enhance the skills of investigators at every stage of their careers. And through our Partner Network, we make available the academic medical resources of institutions throughout the region, and in turn hope to alleviate the health disparities that are so prevalent in the South."

The Mix recently spoke with three of the dozens of researchers whose work has been furthered by the CCTS.

Crafting successful collaborations

The center touches researchers in many different ways, explains Steven M. Rowe, M.D., MSPH, professor of medicine and director of the Gregory Fleming James Cystic Fibrosis Research Center at UAB. Rowe is co-director of the Child Health Research Unit (CHRU), established in 2009 in a partnership among the CCTS, the UAB Department of Pediatrics and Children’s of Alabama. The research unit offers a centralized location and a specialized set of resources that make it ideal for clinical trials.

“This is where we’re doing all our pediatric and adult studies in cystic fibrosis,” Rowe said. Those studies were instrumental in gathering data that led to FDA approval of a new CF treatment, ivacaftor, in 2012. This summer, two new studies, each with significant patient enrollment at UAB, reported that a combination of ivacaftor and an investigational drug named lumacaftor improved lung function in a subset of CF patients. “All that research has been done using the CHRU space in conjunction with the CCTS,” Rowe said. These new drugs treat the underlying defect in CF, and are ushering in a new era of personalized therapeutics, he adds.

CCTS resources are also supporting an exciting new application of Rowe’s research — using ivacaftor as a treatment for chronic obstructive pulmonary disease (COPD). Both are lung diseases, but while CF affects some 30,000 people worldwide, COPD affects more than 10 million Americans and is the nation’s third-leading cause of death. The connection: CF patients are born with a defective gene, CFTR, which means they don’t make enough of a protein that clears mucus from the airways. Several studies from Rowe’s team, all supported by the CCTS, have found that patients with COPD also have reduced CFTR activity through an acquired pathway, and suggest that ivacaftor, which works by activating CFTR, could help. “Now we have an investigator-initiated IND” — an investigational new drug application from the FDA — “to study the use of ivacaftor in adult patients,” Rowe said. The study is now finishing enrollment. “If it works, it could open up a new treatment for COPD,” Rowe said.

“There’s no question that the CCTS helped to make this happen,” he added. “We had no experience with submitting our own IND, or how to interact properly with the FDA in an independent study. We got all that help from the CCTS.”

Creating the infrastructure for innovation

More than a decade ago at the National Institutes of Health, Anath Shalev, M.D., now director of UAB’s Comprehensive Diabetes Center, made a fundamental discovery about the function of insulin-producing beta cells in type 1 diabetes. In response to high blood sugar, she found, beta cells overproduce a protein called TXNIP. This leads to cell death and a decline in the body’s ability to make insulin. Shalev’s research later pointed to a possible treatment — the commonly used blood pressure drug verapamil. In animal models, verapamil lowered TXNIP levels and protected beta cells. In 2014, Shalev received a grant from the Juvenile Diabetes Research Foundation (JDRF) to launch the first human clinical trial of verapamil as a treatment for type 1 diabetes.

“We were able to recruit an experienced nurse from the CCTS to conduct the mixed-meal tolerance test, blood draws and patient education aspects of the study,” Shalev said. “That’s a very important piece. It’s tough to find an experienced nurse to do this work; but through the CCTS, we were able to do it very easily.”

Shalev, who is also a reviewer for NIH study sections, says the presence of a CTSA such as UAB’s CCTS is an important sign of an institution’s ability to carry out a translational trial. “It shows that the institution is committed to doing translational research,” she said. “Funding agencies see that you have the ability to make it happen,” which encourages them to support the work.

Through another CCTS-supported initiative, the Alabama Drug Discovery Alliance, Shalev is investigating another approach to stop TXNIP. “In collaboration with the Southern Research Institute, we have completed a screen of 300,000 small molecules to find a new drug that lowers TXNIP levels more specifically and efficiently than verapamil,” she explained. “We have some very interesting hits and are moving forward with medicinal chemistry on them.”

The CCTS also works with the Comprehensive Diabetes Center to fund translationally oriented pilot feasibility grants to investigators exploring new research concepts. These are a way for investigators to explore innovative ideas, the results of which can lead to greater funding. “The threshold for external grants is so much higher today,” Shalev said. “In a way, you have to have half of the work done before you can get the funding. With a little help up front from pilot grants like these, you can get the crucial preliminary data you need.”

Supporting young investigators

In 2012, Jessica Merlin, M.D., MBA, had just finished clinical fellowships in infectious diseases and palliative care that fueled her interest in a poorly understood topic: the relationship between chronic pain and outcomes in patients with HIV. “I had become interested in this problem while working in Botswana during my residency and fellowships,” said Merlin, an assistant professor in the UAB Division of Infectious Diseases. Chronic pain occurs in anywhere from 39 to 85 percent of patients, “according to which study you look at,” Merlin said. And a patient’s level of pain appeared to have an impact on adherence to therapy. “But very little epidemiological work had been done,” said Merlin.

With a pilot grant from the CCTS, Merlin was able to use the extensive patient database maintained at UAB’s renowned 1917 Clinic to collect preliminary data on the link between chronic pain and health outcomes. She discovered that patients with chronic pain who also recently used illicit substances were actually less likely to miss scheduled appointments. Subsequent work, supported by a K12 grant from the Agency for Healthcare Research and Quality, extended these findings. It also suggested that behavioral intervention could be an important next step in improving chronic pain in this population.

“Having that CCTS grant was a big marker of credibility for me," Merlin said. It also paved the way for a subsequent K23 career development award from the NIH. Merlin is using that funding to pursue a doctorate in the Department of Health Behavior in the UAB School of Public Health to further her research. “The CCTS has been very good to me,” Merlin said. “It’s a great resource to have at UAB.”

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