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Building bridges

Imagine two people standing on opposite banks of a mighty river. Each can see the other, may even be able to hear the other’s calls over the roaring flume, but there is no way—and, considering the swift and deep water, little desire—for them to meet in the middle.

The clinical and research efforts of dental schools are often like those two people, isolated from each other by differences in disciplines that do not facilitate obvious interactions. The clinicians treat patients in the clinics, and the basic researchers add to the body of scientific knowledge from their laboratories.

Under these circumstances, direct application of basic science discoveries to the treatment plan of a patient seems an unlikely outcome. Something has to happen between the laboratory bench and the operatory chair to put the science into a clinical context that benefits the patient.

“Traditionally, the National Institutes of Health had been funding a lot of research that was very fundamental, very cutting edge and it was stuff that we really needed to understand,” said Robert A. Burne, Ph.D., a professor and chairman of oral biology at the University of Florida College of Dentistry. “But it was funded by taxpayers, and the question became, ‘how is this research getting to the patient?’ ”

The NIH recognized translational research was the bridge to span that gap. Translational research requires an interdisciplinary mix of people examining the same problems from different perspectives and bringing the most advanced genetic and molecular tools to bear on improving patient health. This idea became the core of the NIH Road Map initiative, adopted in 2002 to define NIH research funding goals.

In institutions that have strong translational research programs, you’ll see research teams that flow between departments and between missions,” said Burne. “It is a culture that exists in many medical schools, but not in many dental schools, and it is critical, I think, for the future of the profession.”

Planning for change

Aiming to foster a culture change that would bring its research enterprise into alignment with NIH funding priorities to improve patient care, the college was one of a handful of dental schools that applied for and received a one-year, $100,000 NIH Research Infrastructure Planning Grant in 2004. This grant funded an exhaustive strategic needs assessment and planning process that involved college, Health Science Center and university stakeholders.

“The planning grant provided the opportunity for the college to reflect on its history and research accomplishments to date, which enabled a thoughtful articulation of a vision for our future,” said Teresa A. Dolan, D.D.S., M.P.H., a professor and dean of the UF College of Dentistry. “That process was core to the development of our plan to improve oral health through basic, clinical and translational research.”

The end result was an innovative expansion plan, which would use the college’s robust basic science research enterprise as the underpinning on which to build its clinical and translational research efforts. The plan would connect the dots between the college’s research on systemic and oral diseases and the genetics and diabetes research underway elsewhere in the Health Science Center. It would also build “critical mass” within the department of oral biology’s areas of infectious diseases, molecular immunology and cell biology. Overall, the plan would enhance the college’s research activities in the areas of health disparities, caries, periodontal diseases, oral cancers, Xerostomia, and pain.

To achieve this, the plan outlined targeted recruitment of junior research faculty to develop translational research teams made up of basic scientists, translational researchers and clinician-investigators. These teams would establish interdisciplinary links with others involved in the university’s ongoing research initiatives in cancer, diabetes, genetics and neurosciences.

In addition, a Pipeline Program to mentor existing clinical faculty would be established with the goal of positioning them to develop their own NIH-competitive research programs. An internal funding mechanism would provide these mentored researchers with salary and start-up program support.

“We wanted to invest in training for endogenous personnel,” said Burne. “Those would be clinician-scientists unable to gain enough traction to develop hypothesis-driven, cutting-edge research programs by virtue of the fact that they either didn’t have the requisite formal training, and/or could not gain sufficient relief time from their clinical obligations.”

In support of the plan, the Health Science Center committed to assigning another 13,000 square feet of laboratory and office space within the Dental Sciences Building to the College of Dentistry. Additionally, the college and the university’s Division of Sponsored Research agreed to provide match support should NIH fund implementation of the college’s research infrastructure enhancement plan.

Bridging the gap

Not surprisingly, NIH liked what it saw in the plan, and, in 2005, the National Institute of Dental and Craniofacial Research awarded the college $2 million in direct costs under its Enhancement of Research Infrastructure and Capacity Building for Dental Schools (U24) funding initiative. With another $2-million in match support from the university and the College of Dentistry, the award provided a $4-million infusion of cold, hard cash into the college’s research infrastructure plan. The business of implementation could begin.

Young research faculty were hired in the departments of community dentistry and behavioral science, oral biology, oral and maxillofacial surgery & diagnostic sciences, and periodontology. These individuals brought an array of expertise to broaden translational research activities, and much-desired interdisciplinary linkages immediately began forming between clinicians and researchers, within the college and without.

An excellent example of this synergy occurred within the Department of Periodontology where a translational research team seemed to form of its own accord once targeted faculty recruits were in place. Periodontal Chairman Ikramuddin Aukhil, B.D.S., M.S., a recent recruit to the college himself, drew on this synergy after he was contacted by the Leon County Health Department regarding an unusual population of pediatric patients in Tallahassee suffering from advanced and aggressive periodontal disease.

Aukhil and two periodontal faculty members initially visited the clinic to conduct chart reviews and examine the children.

“We were amazed by the magnitude of bone loss around the molars and incisors,” Aukhil said. “The clinic staff said they saw a couple of kids like this each month. That’s a lot, to see a couple of cases a month. It almost qualifies something to be called an epidemic.”

The affected group turned out to be a total of 60 Leon County children, mostly African-American and between the ages of 7 to 20.  Aukhil obtained permission from the university’s human use committee to pursue a more formal project, and he assembled a translational dream team to begin work.

“We’ve put together a team of clinicians, immunologists, pathologists, and microbiologists,” Aukhil said. “Our goal is to collect blood samples, plaque samples, gingival crevice fluid, and, of course, clinical measurements of bone loss and so forth.”

The clinicians in this multidisciplinary group include Aukhil, Luciana Machion-Shaddox, D.D.S., Ph.D., an assistant professor of periodontology with research interests in the relationship between periodontal disease and diabetes mellitus, and Ingvar Magnusson, D.D.S., Ph.D., a professor of oral biology and a seasoned periodontist with published research on the disease progression and treatment of periodontal disease.

Research infrastructure recruit, Shannon Pop, Ph.D., an assistant professor of periodontology, is the team’s immunologist with expertise in inflammatory responses and oral systemic health as it relates to diabetes. She and collaborator Michael Claire-Salzler, M.D., a professor of pathology, immunology and laboratory medicine in the College of Medicine, are conducting immunoassays on the blood samples to tease out the genes and molecules involved in how the host cells respond to bacterial insults.

Clay Walker, Ph.D., a professor of oral biology, is the team’s microbiologist, sussing out which strains of bacteria and enzymes play a dominant role in the childrens’ disease.

Once the team has gathered the clinical, microbiologic, and biochemical data on the children, a disease pattern is likely to emerge which will dictate what treatment strategies can be used to address it, Aukhil said.

Because the disease pattern disproportionately affects African-American children in Leon County, Aukhil intends to submit a grant proposal to NIDCR to fund a broader study of similar patterns of pediatric disease affecting other African-American communities in the state. Geneticists are likely to be included in that study.

“It’s very important for clinicians and basic scientists to interact,” said Aukhil. “There must be a dialog between the two which makes sense and has applications. That’s what we’re trying to do. This is a classic example of a translational theme of research.”

A transformation of character and function

There’s no doubt that the cadre of translational researchers hired through the NIDCR (U24) research infrastructure award serve as a sort of intellectual bridge between the college’s clinical and basic science research enterprises.

“We view the U24 at Florida as a good investment in the future of dental and craniofacial research,” said Kevin Hardwick, D.D.S., M.P.H., NIDCR’s chief of research training and career development. “The school already had a solid research base, but was able to leverage the U24 funds to develop its mid-level faculty to build a more cohesive research program that extends across the various departments in the dental school.”

The approach has really been encouraging to these faculty members, allowing them time to focus on their research,” Hardwick said. “I think the school’s research program is stronger because of this.”

The free flow of people, ideas and research missions facilitated by the new, more dynamic interdisciplinary mix of research faculty has blossomed into surprising interactions between clinicians and basic scientists that directly lead to improved patient care.

I’ll use Valeria Gordan as an example, she’s an associate professor of operative dentistry enrolled in the Pipeline Program,” said Burne.
Gordan received salary support through the Pipeline Program, enabling her to enter the College of Medicine’s NIH-funded K30 training program, which will result in a master’s in clinical investigation. Her research interests are applying basic science findings in cariology to the management of clinical caries, and she has applied for NIH grants toward that end.

We now have a clinical faculty member who has submitted two competitive NIH grant proposals in a three-month time frame to use Real-Time Quantitative PCR, gene expression profiling and measurement of biochemical activities in plaque from caries-active and caries-free subjects to understand why some people get caries,” said Burne. “This is exactly the type of research that will lead to new discoveries and treatments for oral diseases.”

“We’re in much better shape as a college to expand this type of research as a result of support from the U24,” he said.