50 Years of Excellence in Research
Innovative Discovery Advances Improvements in Patient Care
By David Enders
“It is the long history of humankind that those who learned to collaborate and improvise most effectively have prevailed,” Charles Darwin said. And the 50-year evolution of research at the UT Health San Antonio School of Dentistry has proven, beyond a doubt, that collaboration and improvisation are the human key to unlocking unlimited scientific discovery.
The dental school’s evolution began with some old-fashioned political improvisation. In the late 1960s, the state of Texas boasted dental schools in Dallas and Houston, but a new school to address disparities in the underserved communities of South Texas was desperately needed. The new University of Texas Medical School at San Antonio seemed a natural fit. After political wrangling by San Antonio Chamber of Commerce President and Periodontist James P. Hollers, D.D.S., and influential friends, the idea gained traction with the state legislature. The new dental school would leverage existing research labs, equipment, talent and funding momentum at the new medical school to quickly get up to speed.
The UT Dental School at San Antonio opened in 1970 in a modest space available under the Medical School auditorium with an inaugural class of 16 students. By the time Professor John Rugh, Ph.D., joined the faculty in 1977, enrollments were steadily rising, but the research program was still just a good idea. The initial dental school faculty were mostly local practitioners and educators and not necessarily trained scientists, Dr. Rugh recalls, so he developed the school’s first faculty in-service training on research design and methodology and helped kickstart a 10- to 20-year search for established international researchers.
By 1983, there was a renewed sense of urgency. The National Institutes of Health (NIH) reported a critical lack of dental researchers across the nation. “Dental science is in the anomalous position of having extraordinary potential while facing economic pressures that threaten the supply of new investigators,” the NIH opined. Dr. Rugh said, “We knew we wanted both clinical and basic research, but clinical research was more relevant to what we were doing at the time, and I knew the faculty would embrace it.”
THE EARLY DAYS
Within two years, a new clinical research facility with 30 operatories was opened at the dental school, with clinical research and translational science (getting new science into the clinical setting) the primary focus. Research was integrated into the curriculum and student and faculty research abstracts increased from an average of four per year from 1976 to 1979 to an average of 60 per year by 1986. Research awards grew from $700,000 in 1984 to more than $6 million by 1995. The research mentality was clearly taking hold with faculty and students alike.
In 1986, the School of Dentistry was provided its first Institutional Dentist Scientist Award by the National Institutes of Health’s National Institute of Dental and Craniofacial Research to Stanley Holt, Ph.D. Through 1995, this important training program provided a stipend and research support for dentists obtaining a Ph.D. in addition to specialty training. Successful students matriculated through the highly esteemed program.
Dr. Rugh became the dental school’s first director of research in 1991. “I wanted to put San Antonio on the map as a research-intense school rivaling schools like the University of Minnesota and the University of Michigan and others that were carrying the banner at that time.”
In 1994, an Evidenced Based Practice (EBP) program was initiated. “When I was president of the American Association for Dental Research, that was a recurring theme: you see all this research going on in the laboratories and university clinics, but the new science was taking as long as seven to 15 years to find its way into private practice.”
To bolster the new EBP mindset, the web-based CATs (Critically Appraised Topics) library was launched. Students and faculty would identify relevant clinical problem topics, do a comprehensive literature review and critical assessment, and then summarize the research before publishing to the CATs library complete with associated links. The Dental CATs library is indexed on the British TRIP (Turning Research Into Practice) Database, a premier medical search engine. CATs users can comment on the CATs adding the latest clinical findings and insights.
Highly accomplished researchers began arriving on campus in numbers throughout the 1990s, among them Harvard-trained researcher David Cochran, D.D.S., Ph.D., who brought with him his passion for implantology and translational research. “In my view, the UT Health School of Dentistry by that time was already perceived as an outstanding research school,” Dr. Cochran says. “I felt the collaborative attitude was extraordinary and very strongly focused on research activity.”
But he also believed, at least at that time, most dental professionals were by design either great clinicians or great researchers and saw the advantage in bridging that divide. Use the first-hand experience of the problems and frustrations of a clinician, and then go back to the lab to try to solve those problems, he said. “The benefit is translational research, taking advances in science and applying that directly to patient care. To me, that’s the goal of everything we do scientifically is to try to make lives better for patients and improve their care.”
Dr. Cochran’s work was indeed transformational as he found himself serving on the Dental Advisory Panel to the Food and Drug Administration to evaluate new dental products. Dental school products approved included Bone Morphogenetic Protein (BMP-2), a protein commonly used to help grow bone in spinal fusions, but modified to work in the oral cavity, as well as new products and techniques to roughen implant surfaces in order to accelerate bone healing, thereby cutting in half the time for dental implant recovery from about three months to six weeks. Dr. Cochran is currently involved in canine trials for a new “bone glue” which would stabilize dental implants and encourage bone growth.
Mary MacDougall, Ph.D., B.A., was appointed associate professor of pediatric dentistry and director of research for the department in 1993, and by 1996, the dental school was ranked the number one school in the nation by U.S. News & World Report. In 1999, she became the school’s first associate dean of research.
“It was the goal of then Dean Ken Kalkwarf, D.D.S, M.S., to bring the school up in terms of scholarly research,” Dr. MacDougall says. “Like MIT, Harvard and Stanford, institutions have reputations based, in large part, by their contribution to the literature through research. It was almost like a coming of age for our dental school in the 1990s to have that broader impact.”
Research grants grew by leaps and bounds. A $5.5 million National Institute of Dental and Craniofacial Research (NIDCR) program project grant to study tooth formation and the regulation of tooth-specific genes focused on Dr. MacDougall’s specialty area of research. “We were looking at the basic process of how you form a tooth, the process of making very specialized cells that produce a hard matrix that represents the enamel and the dentin. Then, we applied that knowledge for the purpose of engineering a new tooth.”
Dr. MacDougall, who now serves as dean of the Faculty of Dentistry at The University of British Columbia, in Vancouver, British Columbia, said she was most proud of organizing and implementing the COSTAR (Craniofacial Oral-Biology Student Training) program which has been continually funded by NIDCR since 2002. The program offers students assistance in obtaining the D.D.S./Ph.D. dual degree so they are positioned to become the next generation of academic clinician scientists. The dual degree program was dormant for 17 years, Dr. MacDougal says, and was particularly critical, due to an aging faculty and academic research faculty shortages.
“The idea was to create a new pipeline of students to pursue academic career paths. You always hear about the M.D./Ph.D. graduate who is trying to cure cancer, but there really wasn’t that same profile for dentistry. That was something of great interest to the NIDCR. The grant would finance D.D.S./Ph.D. dual-degree students and help us grow our own faculty to help our problem of retiring faculty.” The first dual-degree graduate, Cara Gonzales, D.D.S., Ph.D., is still on staff as an associate professor in the Department of Comprehensive Dentistry.
PAIN RESEARCH TEAM
In 1997, Kenneth Hargreaves, D.D.S., Ph.D., joined the research team and now serves as chair and professor of the Department of Endodontics. He also is a professor in the departments of Pharmacology, Physiology and Surgery. “This school’s Department of Periodontics was internationally known from the work of Kenneth Kornman, D.D.S., Ph.D., on cytokines and inflammatory mediators, and continues to be extraordinarily strong now,” Dr. Hargreaves says. “I am very much focused on pain research having been trained in the pain group at NIH and having set up a pain lab in my position at the University of Minnesota. It was an incredible opportunity to come down to San Antonio and join another prominent pain scientist, Chuck Milam (Stephen B. Milam, D.D.S., Ph.D.) who was chairing the Department of Oral and Maxillofacial Surgery.”
Dr. Hargreaves’ pain and regenerative dentistry research teams have made major advancements over the last two decades. He won the prestigious American Dental Association Gold Medal Award in 2018 for Excellence in Dental Research, but emphasizes any success is shared by the entire team.
“Within the pain group, we run a team science environment, with seven PIs (principal investigators) who all work together. We share the same suite of labs, the same facilities and a joint lab meeting, and we all have the opportunity to pursue our research independently or we can collaborate with the others and our trainees, our residents, our Ph.D. students, and our post-docs. We are all immersed in everyone’s research, so it’s an incredible training vehicle.
“We have well over a dozen projects to better understand pain mechanisms,” Dr. Hargreaves says. “We have focused on classes of drugs that block the release of natural capsaicin. Capsaicin is the stuff in hot chili peppers that causes a burning sensation, and our body makes its own ‘endo-capsaicin’ which is a discovery our lab made over 10 years ago. Now, we are trying to take advantage of that knowledge to develop drugs that interfere with that system to provide pain relief in many conditions, everything from infection-related pain, to cancer pain, to possibly diabetic neuropathy, to patients with second-degree burns, all of which would potentially benefit from this class of non-addictive, non-opioid drugs.”
These drugs would work in the periphery (where most pain begins) rather than through the central nervous system, he explains, thereby avoiding the serious side effects of drugs, like opioids, that seriously impact the brain. “Our thought is that it’s like a light switch. If I can shut the light switch off, I don’t have to worry about what’s happening at the light bulb because there is nothing coming in.”
Another member of the team, Nikita Ruparel, D.D.S, Ph.D., is the PI on research using stem cells as natural factories, injecting the stem cells into patients to encourage their natural cell factories release their own factors to suppress pain. “It’s extraordinary work in terms of implications in cell-based pain control,” says Dr. Hargreaves.
Meanwhile, Anibal Diogenes, D.D.S., Ph.D., professor and vice chair of the Department of Endodontics, is leading clinical trials using stem cells to regenerate dental pulp in necrotic teeth. “We have just finished a six-year study to demonstrate methods to disinfect and then instill the patient’s own stem cells into that space to regrow the tooth itself. This department is the number one cited department in the world in this particular area,” says Dr. Hargreaves.
“We really are, if you will, a full-service pain research group,” Dr. Hargreaves adds, so the research has implications in virtually all health care environments. Pain is usually the first thing that brings a patient into the clinical environment; even during the COVID-19 pandemic, 50 percent of patients report muscle pain. “When I first saw the list of cytokines involved in the disease’s ‘cytokine storm,’ almost every one is a known pain mediator. It is obvious this disease involves pain, so we’ve developed a research group in that area. We’re trying to make lemonade out of some pretty horrible lemons we’ve all been given.”
Notwithstanding the school’s research success in the areas of pain, restorative and regenerative dentistry, the mighty “ounce of prevention” axiom always remains in play. Kevin Donly, D.D.S., M.S., chair and professor of the Department of Developmental Dentistry, says prevention is most important when dealing with children, particularly in the underserved communities. The large underserved community, the diversity, and the school’s relationship with Christus Santa Rosa Hospital (now The Children’s Hospital) is what first drew him to the school. “What a great place to do pediatric clinical care and research.”
Dr. Donly, past-president of the American Academy of Pediatric Dentistry, says amazing progress has been made with restoratives, sedation and pain control to treat young patients, but prevention remains the most impactful. “About 10 years ago, we saw a large increase in the number of dental caries in our 2- to 5-year-olds, and this was unusual considering fluoridation was introduced in 1972.”
Clinical research revealed many of these problems were being passed on by adults, either through poor diet or by passing on their oral bacteria to their young children by sharing spoons, for example. “The key is to get the parents prevention-oriented early on,” Dr. Donly says.
Clinical research toward continuing improvements in health equity across South Texas is the main priority, says Dr. Donly. “We do nearly 30,000 patient visits a year, the majority of which are underinsured. I feel very good about that. We have also placed 28 pediatric dentists in South Texas. It always comes back to the children. When a child actually likes to come and see you, that in itself if very rewarding.”
NEW RESEARCH SITE
In 2015, the School of Dentistry opened the state-of-the-art Center for Oral Health Care and Research. “We now have the opportunity to conduct clinical trials and research at a level we’ve never been able to do before,” Dr. Hargreaves says.
Although a top 10 ranking is difficult to maintain, Brij Singh, Ph.D., current associate dean for research, has no doubts the school’s strong research reputation is secure.
“When I got here, our goal was to move back into the top 15 schools in the country,” Dr. Singh says. “We were able to do that pretty quickly. Then the goal was to move in to the top 10, and that’s where we are now. So now our goal is to move into the top five schools in terms of NIH funding and overall funding.” Translational research will continue to be an overarching theme moving forward, he adds. “Of course, all of the money is useless unless you can use it for the benefit of humankind.”
Dr. Singh’s own research involves how saliva is secreted, and the mechanisms that are working in salivary disease conditions, such as Sjogren’s Syndrome and oral cancer. It holds great promise in understanding just how the oral cavity, the main portal to the digestive and respiratory systems, acts as a gatekeeper for general health, he explains.
Dr. Singh predicts that one day sensors in the oral cavity may be used to detect disease conditions long before they would be detected in the typical blood draw used today. Research success always comes down to extraordinary teamwork, he says. “We are able to do with half the faculty what some of the larger dental school research departments cannot do. The work culture toward a common goal at this school is something which really is beyond comparison of any school I’ve ever seen.”
As the dental school research program continues its evolution, it will prevail as Darwin predicted. “Our environment continues to change, but our culture of open collaboration has remained,” says Dr. Hargreaves. “It’s very unique, and it allows us to accelerate productivity and do what I consider to be true translational science, and I’m thrilled and honored to be a part of a team that is focused on making a difference in people’s lives.”