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The Science of a Smile

Basic science collaboration frames dental medicine research


​CU Dental Fall 2014 Publication

By Lyndsey Crum

Not all dental faculty spend significant time in the school’s clinics. Some find their home on the western edge of the campus, away from the patients and educational classrooms, in the research quadrant of the University of Colorado Anschutz Medical Campus. But that separation doesn’t diminish their connection with the heart of the school, in many ways, it enhances it. 


Situated on the 2nd and 11th floors of two campus research towers, you will find suites of faculty offices and laboratories which are home to the School of Dental Medicine Department of Craniofacial Biology. From here, dental medicine faculty collaborate with scientists in cancer, cellular biology and engineering to advance discoveries in disease treatment and smile restoration. 

 

CONSTRUCTIVE COLLISIONS
These collaborations are critical to what Senior Associate Dean for Research Jeffrey Stansbury, PhD envisions for the future of dental medicine research.
 
“For research to work well you have to have collisions,” states Stansbury, “Intentional and occasionally unintentional collisions of ideas.”
 
Stansbury’s vision is to set up the framework which will support these collisions in order to generate new ideas across the school’s basic science research teams.
 
“We want to support increases in cutting edge research, so we have all of the core faculty looking for collaborative opportunities, whether local or international.”
So far the school’s faculty are meeting that expectation, and this is due in large part to the intentional design of university’s research facilities.

  

A CAMPUS FOR COLLABORATION
When the Anschutz Medical Campus was designed, university leadership made an intentional decision to co-locate the research branches of each school and college faculty into multi-disciplinary facilities. The shared spaces meant faculty from dental medicine could easily connect with colleagues in medicine, the Cancer Center, and the colleges of engineering on both the Denver and Boulder campuses. And they could work together to solve common interest, complex issues like cancer treatments or clinical applications for bioengineering.
 
“I learned a lot about geography when we moved to Anschutz” jokes Professor Mary Reyland, PhD. “The move from 9th and Colorado to Anschutz coincided with the buildup of our faculty,” states Reyland, who was one of the few dental medicine researchers who made the transition from the old campus, to the sprawling, and still growing Anschutz Medical Campus. “Now we are geographically connected to other scientists and the open lab design helps facilitate collaborations.”
 
Since the transition to new facilities, the school has grown the number of research faculty and enhanced their collaborations with clinical and translational scientists who share their research interest in common diseases.
 
These connections and shared areas of focus are what craniofacial biology Chairman Lynn Heasley, PhD sees as the future of research-team science.
 
COLLABORATING TO FIND A CURE
Heasley, a member of the University of Colorado Cancer Center, is leading a research team in its effort to improve drug therapies and possibly find a cure to forms of cancer.
 
Heasley joined the university as a post-doctoral student in 1992 and transitioned his faculty appointment to the dental school in 2007. During his career at CU, Heasley’s expertise in oral cancer grew and his understanding of drug therapy and cancer biology earned the School of Dental Medicine a grant from the U.S. Veterans Administration to study drug therapies for head and neck cancers.
 
According to Heasley, not all cancer cells respond with the same efficacy to a particular drug therapy, so the trick is identifying or personalizing the drug to a specific subset of oral cancers.
 
Currently, head and neck cancers are treated with surgery, radiation and cytotoxic drugs, with little viable option for personalized therapies. It wasn’t too long ago that lung cancer was the same way, until approaches to personalized drug therapy evolved to target different oncogenic cell surface receptors that “drive” the cancer cells in particular patients. Heasley plans to apply that approach to head and neck cancer and he has joined a team of CU scientists to help him do it.
 
At a basic level, cancer is the result of a cell mutation. A normal cell receives instruction on how to grow and function. It receives these instructions from other cells via pathways and receptors – much like an electrical current reaches a switch with the power to turn on a light. Eventually a normal cell will shut the current off. When it doesn’t, it becomes a cancer cell.
 
In the case of some head and neck cancers, Heasley believes that an over expressed receptor, FGFR1, is the switch. This over expression prevents the cell from “turning out the lights” something that he hopes to fix by targeting FGFR1 with personalized drug therapies.
 
Enter University of Colorado School of Medicine colleague Antonio Jimeno, MD, PhD. Jimeno, a University of Colorado Cancer Center oncologist, has collected head and neck cancer cells, known as patient-derived xenografts (PDX), from his oncology practice. The PDX’s are propagated in immune-deficient mouse models, giving Heasley and Jimeno access to live cancer cells to test their hypothesis.
 
The research team will then use existing FDA approved drugs and attempt to block FGFR1 in the mice bearing cancer cells over expressing FGFR1, thus preventing cancer cell growth.
 
“It’s like turning the light switch off,” says Heasley.
 
Moreover, Heasley anticipates that this approach will dramatically reduce the time between their initial study and clinical trials. That reduction may amount to years, which is due in large part to the strong partnership between Heasley’s basic science background and clinical and translational research of his school of medicine colleagues.

 

TRAINING FOR TOMORROW
Future successes like Heasley’s cancer research will require building a pipeline of basic science researchers, something Reyland is taking head-on by directing the university’s cancer biology doctoral program.
Reyland, who also holds a joint faculty appointment in the School of Medicine, leads the inter-departmental program which combines basic biomedical science with applied clinical and translational research in human cancer.
 
“We can’t lose sight of basic science,” states Reyland. “Any advance that we have is based on basic research and we need to bring new people into the pipeline of our profession.”
 
Reyland’s own research provides a home for those advancements as she focuses on the impacts of radiation to the salivary glands, a significant concern for head and neck cancer patients who currently undergo irradiation therapy.
 
Radiation attacks the oral tissue in order to kill the cancer cells, but has the side effect of also killing the nearby salivary gland tissue. According to Reyland the salivary gland cannot replace tissue following irradiation, causing the cancer patient to lose the ability to produce saliva. This loss can radically change a patient’s quality of life following treatment. So, Reyland and colleagues are examining ways to protect the gland and possibly regrow the tissue.
 
Much like other basic science researchers within the university and school, Reyland includes her doctoral students in the effort to advance these discoveries.
 
THE SCIENCE OF A SMILE
Exposing students to the school’s basic science research offers unique insight into how faculty literally engineer the smiles of tomorrow.
 
Senior Associate Dean Stansbury, a biomaterials chemist and bioengineer, directs labs at both the Anschutz Medical Campus and the University of Colorado Boulder, where he offers dental students and graduate students hands on experience in the science of a smile.
 
Run in partnership with the CU Boulder College of Engineering and Applied Science, Stansbury’s labs experiment in the development and polymerization of dental composites and adhesives. Stansbury’s labs utilizes chemistry and bioengineering to create and test the properties of new restorative materials including their brightness, color, durability and shrinkage. From their photo-sensitive materials to new nanogel technology, Stansbury’s lab is finding success.
 
“We’ve been getting a lot of great results in nanogel materials,” states Stansbury. “Making nano materials offers a high degree of conversation but low stress and shrinkage,” something that will make future dental restorations last longer and be stronger.
 
Stansbury’s discoveries have resulted in eight patents issued and five patents pending, plus additional federal and industry sponsored research awards. Stansbury together with Chris Bowman, a Boulder-based faculty also appointed in the dental school are responsible for CU being the recipient of two out of six recent National Institutes of Health grants seeking new polymeric materials that can deliver dental restoratives with extended clinical service lifetimes; while Stansbury’s former post-docs, now working at other institutions, were the recipients of two of the four remaining grants.
 
Any member of the Anschutz Medical Campus would say that this research is clout-worthy, but for real emphasis, just ask Stansbury to smile.
 
Stansbury sports a filling of his own invention after his personal dentist became an earlier adopter of the commercial composite based on materials engineered in the Stansbury lab.
 
So while faculty like Stansbury may not spend their time chair side with dental patients and students, their research collaborations and basic science discoveries are advancing the care and future cures of oral diseases treated just a short walk away in the School of Dental Medicine clinics.

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