UW School of Dentistry

New acid-detecting tool can predict cavities

In a new study, School of Dentistry and other University of Washington researchers have developed a tool that can measure acidity levels of plaque on teeth, which can predict dental caries, or tooth decay.

A prototype scanner developed by University of Washington researchers can read acidity levels on teeth painted with fluorescent dye to find where they are at highest risk of dental decay.
A prototype scanner developed by University of Washington researchers can read acidity levels on teeth painted with fluorescent dye to find where they are at highest risk of dental decay.  Photo: University of Washington and IEEE Xplore/Creative Commons

The UW device, called an O-pH system, is a prototype that emits LED light which, when used on an FDA-approved chemical dye that patients apply to their teeth, measures the pH levels built up by bacteria in their plaque.

“What our system does is detect the pH of the tooth’s surfaces in order to predict when, or how, bacterial processes will take over,” said Dr. Alireza Sadr, a School of Dentistry faculty member and study-co-author, “and to also determine the risk of each surface of developing caries.”

“Plaque has a lot of bacteria that produce acid when they interact with the sugar in our food,” said Manuja Sharma, a doctoral student from the UW Department of Electrical and Computer Engineering and lead author of the study, in a UW News release. “This acid is what causes corrosion of the tooth surface and eventually cavities. So, if we can capture information about the acidic activity, we can get an idea of how bacteria are growing in the dental biofilm or plaque.”

In early testing, the research team recruited 30 patients between the ages of 10 and 18, with a median age of 15, in the UW School of Dentistry’s Center for Pediatric Dentistry, since the enamel on children’s teeth is more susceptible to acid erosion.

The idea for the technology behind the device came from Dr. Eric Seibel, senior author and research professor of mechanical engineering in the UW College of Engineering, who initially worked on the project with former UW dental dean Dr. Joel Berg.

According to Dr. Sadr, the future applications of the O-pH device could reduce the need for dental X-rays. “Instead of going to the dentist and getting X-rays annually, you could go to the dentist and get an Oral-pH scan, and it’s almost more meaningful,” said Dr. Sadr. “Our goal is to limit the amount of X-ray exposure to the patient, and I think this technology will help with that.”

The current version of the O-pH device can assess roughly the surface area of one tooth at a time. A potential next step would be to utilize a high-speed camera to capture multiple surfaces in less time for a reading of all of a patient’s teeth in under a minute.

According to Dr. Sadr, the research team is working with other School of Dentistry and UW departments to prepare for clinical testing of this new video-based O-pH instrument.

Other co-authors of the study from the School of Dentistry include David Park, Se An, Micah Bovenkamp, Jess Cayetano, Ian Berude, and Zheng Xu, along with Lauren Lee from the UW Department of Microbiology, and Matthew Carson from the UW Human Photonics Laboratory. This research was funded by the National Science Foundation, award IIP-1631146 “Oral Health Monitor – optical quantification of bacterial load, therapy monitoring, and caries prediction.” Support also came from the Institute of Translational Health Sciences and the National Center for Advancing Translational Sciences of the National Institutes of Health.

Research takes spotlight at school’s annual event

Dr. Rachel Kehr
Rachel Kehr

Dr. Rachel Kehr and Deborah Lee took first place in the Graduate Student Research Competition and Dental Student Research Competition respectively at this year’s School of Dentistry virtual Research Day.

Dr. Kehr, who was mentored by Dr. Avina Paranjpe, received her DDS from the school in 2020 and is now a resident in the Department of Endodontics. She received $500 from both the national and Seattle sections of the American Association of Dental, Oral and Craniofacial Research (AADOCR) and will present her work at the March 2023 International Association for Dental Research (IADR)/AADOCR meeting.

Deborah Lee
Deborah Lee

Lee, a second-year student mentored by Dr. Hannele Ruohola-Baker, received $200 from the Sigma Sigma Chapter of the Omicron Kappa Upsilon National Dental Honor Society, and will represent the School of Dentistry at next year’s AADOCR Student Competition for Advancing Dental Research and Its Application.

Alaa Alkhateeb, mentored by Dr. Donald Chi, was runner-up in the Graduate Student Research Competition, and will replace Kehr if she is unable to attend the IADR/AADOCR meeting.

Second-year students Lauren Lee, mentored by Dr. Zee Liu, and Madelyn Koh, mentored by Dr. Chi, received second and third place respectively in the Dental Student Research Competition, and will receive $150 and $100 for their projects.

Su-In Lee, PhD
Su-In Lee

Dr. Su-In Lee, a professor at the UW’s Paul G. Allen School of Computer Science and Engineering, gave the keynote presentation, titled “Explainable Artificial Intelligence in Healthcare.” Her research aims to advance how artificial intelligence can be integrated with biomedicine.

School of Dentistry faculty also gave presentations. Dr. John A. Sorenson’s subject was “Digital Prosthodontics – Ready for Private Practice or Just Glitzy Hype?” Dr. Roozbeh Khosravi presented his research on thermoforming plastic and 3D printed aligner-like devices in orthodontics, while Dr. Alireza Sadr discussed “Development of Optical Coherence Tomography: Benchside to Chairside.”

Social and behavioral scientists join forces for oral health

Dr. Cameron Randall
Dr. Cameron Randall

A large group of behavioral and social scientists, led by Dr. Cameron L. Randall of the University of Washington and Dr. Daniel W. McNeil of West Virginia University, are on a mission to throw the combined weight of their disciplines behind the effort to improve oral health globally.

“We’re trying to maximize the application of the behavioral and social sciences to oral health research and practice,” said Dr. Randall, a psychologist and member of the Department of Oral Health Sciences faculty at the School of Dentistry. “Are they being applied as robustly as possible, in the highest quality and most innovative ways?”

He and many of his colleagues think there’s substantial room for improvement in oral health research methods and in approaches to patients and the public in general.

“Because everyone’s oral health is strongly influenced by things like their environment, diet, health and oral hygiene behaviors, and access to and utilization of evidence-based interventions, there is much opportunity for impact if the behavioral and social sciences are fully tapped,” Dr. Randall said.

To that end, he and Dr. McNeil led the writing of a consensus statement for this movement that appeared Jan. 19 in the Journal of Dental Research, which is published by the International Association for Dental Research.

The statement, which has more than 400 endorsers, grew out of a three-day Behavioral and Social Oral Health Sciences Summit held in 2020. The virtual meeting, the first such international gathering of its kind, drew more than 400 people from 57 countries. After the meeting, the statement was produced with input from global stakeholders and several rounds of refinement. It reflects the current state of knowledge in the behavioral and social oral health sciences and identifies key future directions for the field.

Dr. Randall and his colleagues hope their efforts will spur broader conversations about translational science – which transforms discoveries into real-world practical applications – and multidisciplinary science, especially in dentistry and oral health.

“There is opportunity to better tap advances in disciplines such as psychology, sociology, economics, and political science,” he said. “We can tap innovations and current thinking in those areas and apply them to oral health interventions.”

Dentists and other oral health providers are prime targets for the movement. Dr. Randall noted that part of the consensus statement examines more immediate applications, such as clinicians’ use of innovative technology and person-centered approaches to promote behavioral change and prevent and treat dental disease.

He said, “We’re raising questions to be answered: What are the most effective behavioral interventions for patients? How can we motivate clinicians to quickly adopt these and other evidence-based interventions? How can we encourage them to use these approaches consistently?”

The target audience ranges well beyond dentists and other providers, too, he said. There’s a role for behavioral and social scientists to think about how to work with the community and community organizations to develop contextually appropriate oral health programs related to prevention and other goals.

He and his colleagues will also seek answers to this question: “How can behavioral and social scientists help develop structural changes to prevent dental disease and make oral health-care delivery more effective, accessible, and equitable?”

Even a seemingly unrelated field like economics can supply useful insights, Dr. Randall said, citing the example of taxing sugar to change consumer behavior. Research by Dr. Kristine Madsen of the University of California, Berkeley School of Public Health has found that taxes on sugar-sweetened beverages can significantly reduce their consumption, especially in low-income and diverse neighborhoods. These communities display the highest rates of obesity and diet-related chronic diseases such as diabetes and dental decay.

The next step for Dr. Randall and his colleagues will be addressing the gaps they’ve identified in current approaches to oral health research and interventions. “We’re asking people to fill those gaps,” he said. “We want the maximum impact for patients and providers alike. Thus, we want to make oral health researchers and other stakeholders aware of the consensus statement.”

The writers and endorsers of the statement hope the specific suggested future directions for research and its application will be good for science, patients, and communities, he said. Their aims are nothing if not ambitious. As Dr. Randall said: “This group is trying to determine what oral health equity looks like on a global scale and how to fully harness the behavioral and social sciences to help achieve it.”

UW researchers reveal new aspects of gum disease and body’s protective response

A team led by University of Washington researchers has, for the first time, identified and classified how different people respond to the accumulation of dental plaque, the sticky biofilm that gathers on teeth. Their work, just published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS), sheds important new light on why some people may be more prone to serious conditions that lead to tooth loss and other problems.

Taking gingivitis sample from patients mouth
A sample of oral bacteria is taken from a study subject. Photo credit: Dr. Shatha Bamashmous

Left unchecked, plaque buildup can induce gingivitis, or gum inflammation. Gingivitis, in turn, can lead to periodontitis, a serious gum infection that damages the soft tissue and can destroy the bone that supports teeth. Not only can this result in tooth loss, but chronic inflammation can also spur other serious health consequences, including heart disease, diabetes, cancer, arthritis, and bowel diseases.

The researchers also found a previously unidentified range of inflammatory responses to bacterial accumulation in the mouth. When bacteria build up on tooth surfaces, it generates inflammation, a tool the body uses to tamp down the buildup. Previously, there were two known major oral inflammation phenotypes, or individual traits: a high or strong clinical  response and a low clinical response. The team identified a third phenotype, which they called “slow”: a delayed strong inflammatory response in the wake of the bacterial buildup.

The study revealed for the first time that subjects with low clinical response also demonstrated a low inflammatory response for a wide variety of inflammation signals.  “Indeed, this study has revealed a heterogeneity in the inflammatory response to bacterial accumulation that has not been described previously,” said Dr. Richard Darveau of the UW School of Dentistry, one of the study’s authors.

His School of Dentistry colleague and study co-author Dr. Jeffrey McLean said, “We found a particular group of people that have a slower development of plaque as well as a distinct microbial community makeup prior to the start of the study.” The study authors wrote that understanding the variations in gum inflammation could help better identify people at elevated risk of periodontitis. In addition, it is possible that this variation in the inflammatory response among the human population may be related to the susceptibility to other chronic bacterial-associated inflammatory conditions such as inflammatory bowel disease.

In addition, the researchers found a novel protective response by the body, triggered by plaque accumulation, that can save tissue and bone during inflammation. This mechanism, which was apparent among all three phenotypes, utilizes white blood cells known as neutrophils. In the mouth, they act something like cops on the beat, patrolling and regulating the bacterial population to maintain a stable condition known as healthy homeostasis.

In this instance, plaque is not a villain. To the contrary, the researchers said that the proper amount and makeup of plaque supports normal tissue function. Studies in mice have also shown that plaque also provides a pathway for neutrophils to migrate from the bloodstream through the gum tissue and into the crevice between the teeth and gums.

When healthy homeostasis exists and everything is working right, the neutrophils promote colonization resistance, a low-level protective inflammatory response that helps the mouth fend off an excess of unhealthy bacteria and resist infection. At the same time, the neutrophils help ensure the proper microbial composition for normal periodontal bone and tissue function.

The researchers’ findings underscore why dentists preach the virtues of regular brushing and flossing, which prevent too much plaque buildup. “The idea of oral hygiene is to in fact recolonize the tooth surface with appropriate bacteria that participate with the host inflammatory response to keep unwanted bacteria out,” Dr. Darveau said. The bacteria start repopulating the mouth’s surfaces spontaneously and almost immediately afterward, Dr. Darveau said.

This research was part of a PhD thesis for Dr. Shatha Bamashmous, a clinician scientist in Dr. Darveau’s laboratory, and was conducted by a team researchers that included Dr. McLean, co-communicating author and colleague in the UW School of Dentistry’s Department of Periodontics; Dr. George Kotsakis of the University of Texas Health Science Center and formerly a UW Department of Periodontics member; Kristopher Kerns of the UW dental school’s Department of Oral Health Sciences; Dr. Brian Leroux, a biostatistician with the school’s Department of Oral Health Sciences; and Dr. Camille Zenobia, Dr. Dandan Chen, and Dr. Harsh Trivedi of the Colgate-Palmolive Company’s Department of Oral Health Research.

Trials begin on lozenge that rebuilds tooth enamel

Before too long, you may be able to buy a breath mint that rebuilds your tooth enamel while it whitens your teeth, thanks to a team of University of Washington researchers.

The team is preparing to launch clinical trials of a lozenge that contains a genetically engineered peptide, or chain of amino acids, along with phosphorus and calcium ions, which are building blocks of tooth enamel. The peptide is derived from amelogenin, the key protein in the formation of tooth enamel, the tooth’s crown. It is also key to the formation of cementum, which makes up the surface of the tooth root.

Each lozenge deposits several micrometers of new enamel on the teeth via the peptide, which is engineered to bind to the damaged enamel to repair it while not affecting the mouth’s soft tissue. The new layer also integrates with dentin, the living tissue underneath the tooth’s surface. Two lozenges a day can rebuild enamel, while one a day can maintain a healthy layer. The lozenge – which can be used like a mint – is expected to be safe for use by adults and children alike.

Graphic of calcium building lozenge
The lozenge uses a genetically engineered peptide, along with phosphorus and calcium ions, to build new layers of enamel on teeth.

The researchers have been discussing commercial applications with potential corporate partners, according to Professor Mehmet Sarikaya, the team leader. He is a professor in the Department of Materials Research Science and Engineering and adjunct professor in the Department of Oral Health Sciences. Also playing a critical role is Dr. Sami Dogan of the School of Dentistry’s Department of Restorative Dentistry faculty.

The lozenge produces new enamel that is whiter than what tooth-whitening strips or gels produce. It has another distinct advantage: Conventional whitening treatments rely on hydrogen peroxide, a bleaching agent that can weaken tooth enamel after prolonged use. Since tooth enamel can’t regrow spontaneously, the underlying dentin can be exposed, with results ranging from hypersensitivity to cavities or even gum disease. The lozenge, on the other hand, strengthens, rebuilds, and protects teeth.

While fluoride can also fortify tooth enamel, it does not actively rebuild it. It also dilutes relatively quickly, and its overall effectiveness depends largely on diligent oral hygiene. At the same time, the lozenge can also be used in conjunction with fluoride, Dr. Dogan said. The fluoride can be in a very low concentration, he added – about 20 percent of what is found in most fluoride toothpastes.

“We have three objectives in the clinical trial,” Professor Sarikaya said. “First, demonstrate efficacy. Second, documentation. Third, benchmarking – seeing how the whitening effect compares to existing commercial treatments.” The researchers have already tested the lozenge on extracted teeth from humans, pigs, and rats, and also on live rats.

The team also plans to develop related products for use in dental offices, Dr. Dogan said, expecting this phase of trials to start in March or April. “Each study will take two weeks, and we expect these trials to take no more than three months,” he said. The team is also developing a toothpaste for over-the-counter use, but has not fixed a timetable for its introduction.

In addition, the researchers are investigating a gel or solution with the engineered peptide to treat hypersensitive teeth. This problem results from weakness in the enamel that makes the underlying dentin and nerves more vulnerable to heat or cold. Most common products currently on the market can put a layer of organic material on the tooth and numb nerve endings with potassium nitrate, but the relief is only temporary. The peptide, however, addresses the problem permanently at its source by strengthening the enamel.

The idea for the lozenge design originated with Deniz Yucesoy, a graduate student in the UW’s Genetically Engineered Materials Science and Engineering Center who received a $100,000 Amazon Catalyst grant through CoMotion, UW’s commercialization center, to support the initial project. Key contributions also came from Hanson Fong, a research scientist in the Department of Materials Science and Engineering.

New grant supports researcher training in UW-Kenya partnership

The Timothy A. DeRouen Center for Global Oral Health at the UW School of Dentistry has received a grant from the UW Global Innovation Fund to help train junior researchers in Kenya in skills to facilitate publishing their work.

The grant helps support a partnership between the UW and the University of Nairobi that goes back more than 25 years. In 2016, the DeRouen Center and the University of Nairobi launched an ambitious effort to combat the oral consequences of the human immunodeficiency virus (HIV) among Kenya’s children. The Children’s Healthy Oral Management Project (CHOMP) also involved the UW Department of Global Health in an effort to train pediatric dentists, community oral health officers, and nurses to screen and treat children’s HIV-related oral issues.

The new funding will go to train junior Kenyan researchers to publish their research work by implementing a curricular program in manuscript writing. The grant will also provide support for journal submission fees. The goal is to enhance representation in scholarly journals and boost opportunities for collaborative publication among the Kenyan trainees.

The Global Innovation Fund distributes awards through the UW Office of Global Affairs. The awards support research collaborations that advance interdisciplinary efforts around the world.

Oral health summit to focus on behavioral science

Oral health isn’t just about teeth. Thoughts and behaviors also play a big part.

Dentists have long known the importance of influencing people’s behaviors and attitudes to promote healthy teeth and gums. That explains a good deal of the impetus for the Behavioral and Social Oral Health Sciences Summit, which will be held this Thursday and Friday in a virtual space.

The summit, which features School of Dentistry faculty members in prominent roles, was originally scheduled as a symposium to take place ahead of the 2020 annual meeting of the International Association for Dental Research (IADR). When the COVID-19 pandemic forced the postponement of the IADR meeting, though, the summit was reinvented to be hosted virtually.

Interest in the event has been strong. Dr. Cameron Randall of the UW Department of Oral Health Sciences, a summit co-organizer, said Wednesday that registration exceeded 550 attendees, which was far more than initially expected.

“We have planned the summit and follow-up activities and publications to advance the application of behavioral and social sciences in dentistry and oral health research,” he said. “We hope this will cement past contributions and usher in a new wave of contemporary contributions to the field.”

While summit panels will discuss big-picture topics such as conceptual frameworks and methodologies, they will also focus on specifics such as research priorities, intervention strategies, and pain management that de-emphasizes opioid use.

Dr. Randall will be joined at the summit by Dr. Lisa Heaton of the UW Department of Oral Health Sciences. Both are clinical psychologists, and both are session co-chairs and members of the summit’s steering committee.

One session panel also includes Dr. Samuel Dworkin, a School of Dentistry professor emeritus and celebrated researcher who was a pioneer in introducing behavioral sciences into dental education. Dr. Dworkin, who co-authored an early book in the field, advocated for dentists to consider not only the physical aspects of treatment but the patient’s behavioral patterns and emotional state. In 2005, he received the Norton M. Ross Award for Excellence in Clinical Research, the American Dental Association’s highest research honor, for his work on the diagnosis and treatment of temporomandibular disorder and orofacial pain.

At the School of Dentistry, Dr. Randall’s and Dr. Heaton’s work has included treating patients’ dental phobias. In a clinical approach begun at the school in the 1970s, they have used desensitization therapy as a key psychological tool to help patients manage those fears while receiving dental treatment at the same time. Drs. Randall and Heaton also provide clinical services in the School of Dentistry’s oral medicine clinic, helping patients manage orofacial pain. Both maintain active programs of research on a variety of topics in behavioral dentistry.

A full summit program, including individual presentations, can be found here.

Ultra-small, parasitic bacteria found in groundwater, moose – and you

Inside your mouth lives a group of bacteria whose closest relatives can also be found in the belly of a moose, in dogs, cats, and dolphins, and in groundwater deep under the Earth’s surface. In a noteworthy discovery, scientists led by a UW School of Dentistry researcher have found that these organisms have adapted to these incredibly diverse environments without radically changing their genetic makeup, or genomes.

Saccharibacteria are found in humans, a range of other mammals, and in groundwater. The nano-sized parasitic bacteria (stained red) can be seen in the upper right.
Saccharibacteria are found in humans, a range of other mammals, and in groundwater. The nano-sized parasitic bacteria (stained red) can be seen in the upper right.

The organisms are members of the TM7 family, also known as Saccharibacteria. These are ultra-small parasitic bacteria with small genomes that belong to a larger group called the Candidate Phyla Radiation (CPR). These CPR bacteria are referred to as “microbial dark matter” that represent more than 25 percent of all bacterial diversity, yet we know very little about them since the vast majority have defied attempts to culture them in the lab.

In research first published as a pre-print in 2018, and now formally in the journal Cell Reports, scientists describe their findings that Saccharibacteria within a mammalian host are more diverse than ever anticipated. The researchers also discovered that certain members of the bacteria are found in the oral cavity of humans, the guts of other mammals, and in groundwater. While these environments are all very different, the bacteria’s tiny genomes remain minimally changed between humans and groundwater. This indicates that humans acquired the bacteria more recently, on an evolutionary timescale.

“It’s the only bacteria we know that has hardly changed when they adapted to humans,” said Dr. Jeffrey McLean, a microbiologist and associate professor of periodontics at the School of Dentistry, and lead author of the paper.

The TM7 bacteria were a complete mystery to scientists until Dr. Xuesong He first isolated the bacterium TM7x, a member of CPR, in 2014. Dr. He is co-author of the paper and associate staff member at the Forsyth Institute of Cambridge, Mass., a leading center of dental and craniofacial research. Since then, researchers have learned that CPR includes a huge number of different bacteria, all with tiny genomes. These bacteria need a host to survive and are unique in that they can’t make their own amino acids and nucleotides, which are essential building blocks for life.

“I see this as a huge discovery,” said Wenyuan Shi, CEO and chief scientific officer at the Forsyth Institute and also co-author of the paper. “This creature survives in both humans and groundwater, which indicates there are similarities that allow these bacteria to adapt to humans.”

Previous research by another co-author, Dr. Batbileg Bor of the Forsyth Institute, showed that TM7 can easily jump from one bacterial host to another. This could explain how they ended up in mammals, since mammals drink groundwater.

“The most likely reason we see a large diversity of these bacteria in humans, yet one group of bacteria remains nearly identical to those in groundwater, is that some groups were acquired in ancient mammal relatives and they expanded over time across mammals, whereas this one highly similar group more recently jumped directly into humans,” Dr. McLean said.

TM7 and other ultra-small, parasitic bacteria within CPR may play important roles in health and disease that we have yet to discover. Since they act as parasites – living with and killing other bacteria – TM7 could change the overall microbiome by modulating the abundance of bacteria, Dr. McLean said. Scientists are just scratching the surface of understanding how much our microbiome, which is the human body’s full microbial population, impacts our overall health. TM7, for one, thrives under the conditions found in oral diseases such as gingivitis and periodontitis.

Another major contribution of this research has been developing a systematic way to name these newly discovered bacteria, setting the foundation for classifying other isolated strains.

The discovery that humans acquired TM7 recently has broader implications for understanding our co-evolutionary pathways with the microbes that live on and within us.

“There are only a couple hundred genes that are different in these ultra-small bacteria between what lives deep in the subsurface environment and those that have become common bacteria in our mouths,” Dr. McLean said. “That is a remarkable feat for bacteria missing so many genes and has to make a living by feeding off other bacteria.”

UW researchers learning how to fine-tune immune response

A pair of studies led by University of Washington researchers has cast important new light on the body’s response to viral or bacterial invaders. In particular, they are learning how that immune response might be controlled to target the response more tightly and limit the collateral damage on this biological battleground.

When a microorganism or toxin enters the body, the immune system swings into action, sending white blood cells known as lymphocytes to fight the invaders. T-cells and B-cells, which are specialized forms of these lymphocytes, attack the source of infection. But in the course of this fight, the T-cells also spur inflammation, which can severely damage tissue. Some of these T-cells are also critical for tissue repair and resolving inflammation, but it has remained unclear if the balance can be tipped to favor tissue repair over inflammation.

The CCR5 protein, which is stained green in this slide, acts like a GPS device for the cells of the immune system, steering them around tissues.
The CCR5 protein, which is stained green in this slide, acts like a GPS device for the cells of the immune system, steering them around tissues.

Now, Dr. Douglas Dixon, Dr. Martin Prlic, and their research colleagues are advancing our knowledge of how to possibly tip the balance of these T-cells to limit the collateral tissue damage. Dr. Dixon is a clinical associate professor of periodontics at the School of Dentistry, and Dr. Prlic holds faculty appointments in the Molecular and Cellular Biology Program at the UW and at Seattle’s Fred Hutch Cancer Research Center.

“We’re gaining a better understanding of chronic inflammation,” Dr. Dixon said. “The possibilities include localized treatment to block inflammation or turn up the immune response, depending on the need. You can design a molecule to bind to a receptor and turn it on or off as needed.”

A key finding has been that while the body rushes reinforcements to the site of an attack, they may not be needed – the defenders already residing at the site may be able to handle the job. Most importantly, these defenders also have the ability to rebuild tissue. That’s what the researchers discovered in a study published in the Science Translational Medicine journal. They investigated a protein called CCR5, which acts as a GPS for cells of the immune system and guides them around tissues but can also be a “back door” for HIV to enter and spread throughout the body.

Anti-HIV drugs that work on blocking CCR5 to prevent infection also block that GPS function. However, the researchers found that the T-cells already residing in the tissue aren’t affected.

“So if you block new T-cells from entering the site of the infection, you may be able to prevent damaging inflammation while the resident T-cells handle the infection and carry out repair functions,” Dr. Dixon said.

A second study, published in the ImmunoHorizons journal of the American Association of Immunologists, focused on the MAIT cell, an unusual type of T-cell that can sense the presence of bacteria.

MAIT stands for mucosal associated invariant T-cell. When one of these cells are exposed to inflammation, they quickly generate-the protein CTLA-4, which the researchers say is basically an “off” switch for the immune response.

“Now we’re working on identifying ways to turn these cells on and off for therapeutic purposes,” Dr. Dixon said.

Drs. Dixon and Prlic are studying how inflammation is regulated in oral tissues, but the implications are wide-ranging. Chronic inflammation has been implicated in many illnesses ranging from gingivitis to heart disease. However, Dr. Dixon said, inflammation is not necessarily a bad thing at a sufficiently low level. “There’s always a background level of inflammation in the mouth and the gut,” he said, adding that it’s actually a protective “sentinel state.”

“But some patients’ immune system just can’t resolve or respond appropriately during an infection, and we’re trying to figure that out,” he said. “You can’t have an unbridled immune response – there would be massive tissue destruction. The challenge is to know how to turn immune cell functions off and on as necessary.”

Using their discoveries, Drs. Dixon and Prlic recently applied for additional National Institutes of Health funding to support the development of therapies to halt chronic inflammation and induce tissue repair.

“I am excited to keep working with Doug on trying to figure out how we can best tweak the immune response to resolve inflammation and enhance tissue repair,” Dr. Prlic said.

Students’ studies showcased during Research Day

Apichai Yavirach, a student in the School of Dentistry’s Department of Oral Health Sciences, and Courtney Lang, a second-year dental student, won top recognition for their poster presentations at the School of Dentistry’s annual Research Day on Tuesday.

Apichai Yavirach
Apichai Yavirach

Yavirach earned top honors among graduate students for his study titled “Engineered osteoclasts resorb  necrotic bone in MRONJ mouse model.” Lang won the predoctoral competition for her study titled “Preventive dental care use for children with special needs.” She will represent the School of Dentistry at next year’s American Association for Dental Research annual student research competition.

Courtney Lang with Dr. Albert Chung of the School of Dentistry faculty
Courtney Lang with Dr. Albert Chung of the School of Dentistry faculty

The predoctoral runners-up were Fang Sun, whose study was titled “Inhibition of oral biofilm formation by zwitterionic nonfouling coating,” and Sophia Cohanim, whose study was titled “Management of dental emergencies in a hospital emergency department.” The presentations were displayed in the main lobby of the UW Health Sciences building.

Dr. Peter Milgrom, professor emeritus of the Department of Oral Health Sciences, started the day with a keynote talk at the Husky Union Building, titled “Evolution of the standard of dental care: research lab to market.”

Dr. Peter Milgrom
Dr. Peter Milgrom

He focused primarily on non-surgical treatments for dental disease such as fluoride varnish and silver diamine fluoride, especially the latter. “We’ve largely treated caries (tooth decay) as a surgical disease, despite what we’ve known since the 1960s,” he told listeners.

Fluoride varnish, introduced in Washington in 1995, has become a popular anti-decay treatment for children. However, as he noted, silver diamine fluoride – which is also applied directly to tooth surfaces – has rapidly gained currency since its introduction in 2015. Dr. Milgrom called it “the most rapid change [in the standard of care] in the history of dentistry.”

New research indicates that the silver is incorporated into the tooth’s dentin, the hard tissue under the enamel, where it strengthens the layer, he said. The treatment, he said, also remineralizes deep lesions in the tooth without inflaming the pulp.

Other faculty giving talks were:

  • Christy McKinney of the Seattle Children’s Research Institute, who spoke on “A global perspective on conducting clinical research to inform practice.”
  • Carrie Heike of the Seattle Children’s Hospital Department of Pediatrics, who spoke on “Integrating caregiver observations into research and health care in infants with clefts of the lip and palate.”
  • Joana Cunha-Cruz of the Department of Oral Health Sciences, who spoke on “Practice-based research for evidence-based practice.”

Anti-aging drug holds promise for age-related oral diseases

A team led by two UW researchers has found that a transplant drug with anti-aging properties can regenerate bone and decrease gum inflammation, pointing the way toward new treatments for common dental problems in aging patients.

Dr. Jonathan An and Dr. Matt Kaeberlein of the School of Dentistry, along with their colleagues across the country, have been studying rapamycin. Rapamycin is approved by the Food and Drug Administration to prevent organ transplant rejection and has been shown in pre-clinical studies to slow aging and increase lifespan in a variety of species, from worms to mice.

Dr. Jonathan An (left) and Dr. Matt Kaeberlein
Dr. Jonathan An (left) and Dr. Matt Kaeberlein

Until now, however, nobody has explored the effect of rapamycin in the aging mouth. There, people also commonly experience age-related decline and diseases, such as bone loss and gum inflammation leading to periodontal disease.

“As dentists, we see our patients over the span of their life,” said Dr. An, an acting assistant professor of oral health sciences. “As our patients grow older, we as dentists see clinically firsthand the underlying consequences of aging in the mouth, such as increased risk for periodontal disease, root cavities, or low saliva. And many of the treatments we currently provide address the symptoms rather than the underlying cause – which is age. With what we’ve learned about rapamycin, there are a lot of possibilities to look anew at a number of dental conditions.”

These photos show an old mouse before and rapamycin treatment. White arrows indicate areas where there is more bone after rapamycin treatment.
These photos show an old mouse before and after rapamycin treatment. White arrows indicate areas where there is more bone after rapamycin treatment.

In their studies of rapamycin in old mice, the researchers found another intriguing effect: The drug significantly changed the oral microbiome, which is the mouth’s bacterial population. They discovered that old animals not only had a different oral microbiome than the young animals, but that rapamycin treatment reversed changes in the old oral microbiome, making it more similar to what was found in  younger animals.

Dr. Kaeberlein, a biologist who also holds an appointment in the UW School of Medicine as a professor of pathology, is co-director of the Dog Aging Project. where he is investigating rapamycin’s anti-aging properties in companion dogs.

The researchers caution that much work remains to be done before human clinical treatments with rapamycin become a reality. While both male and female mice saw their lifespan extended with rapamycin, the effects are stronger in females than in males. Also, even though the drug is approved for use in humans, the researchers must determine the optimum dosage for bone regeneration or microbiome de-aging, as well as the best mode of application.

The researchers plan to publish their results in a journal and have submitted their manuscript to peer review. In the meantime, the results have been posted on the pre-print server bioRxiv.

“We’re asking ourselves now: What’s happening in the mouth as a function of age, and can we target these biological changes with interventions to extend the oral health span?” Dr. An said. “What makes this so exciting is that we could potentially be supplementing fundamental ideas of oral health, where by targeting the biological aging processes we may be able to provide a unique approach toward prognostics, diagnostics, and even the treatment of age-related dysfunction in our mouths.”

New study questions value of fluoride varnish

Fluoride varnish has become a popular anti-cavity treatment for children, and it isn’t hard to see why. It’s relatively easy to apply, and not just for dentists or dental hygienists. Pediatricians can do it as well, with minimal instruction. The sticky varnish goes on with a brush and then dries in a few hours. There’s little risk of children swallowing the fluoride, as they might with other topical treatments such as gels.

Dr. Joana Cunha-Cruz headshot
Dr. Joana Cunha-Cruz

Nor is it very expensive, with treatment costs generally ranging from about $25 to $55. That doesn’t seem to be a prohibitive price to pay to guard a child against tooth decay.

Yet a new study by two University of Washington researchers and their colleagues questions the cost-effectiveness of fluoride varnish for preschoolers and calls its anti-cavity effects “modest and uncertain” in this age group.

Dr. Joana Cunha-Cruz and Dr. Philippe Hujoel of the UW School of Dentistry and four research colleagues came up with their conclusion after reviewing 20 clinical trials of fluoride varnish in 13 countries. They examined trials in which fluoride varnish was used by itself or in an oral health program, and also checked the results of using fluoride varnish compared with placebo, usual care, or no treatment.

“As much as we want fluoride varnish to be effective, the current evidence doesn’t support a huge benefit for its use in young children,” Dr. Cunha-Cruz said.

Dr. Philippe Hujoel
Dr. Philippe Hujoel

In their new study, which was recently published in the journal Caries Research, she and her colleagues noted that fluoride varnish applications are aimed especially at children with a high risk of caries, or tooth decay. It’s not considered a primary form of treatment, but rather a complement to other fluoride treatments such as toothpaste or fluoridated water.

Nonetheless, the researchers reported that more recent clinical trials in both low-risk and high-risk groups “failed to show a protective effect of fluoride varnish applications.”

“Cost-effectiveness analyses are needed to assess whether fluoride varnish should be adopted or abandoned by dental services,” they said in their study.

The researchers don’t assert that fluoride varnish doesn’t work. Their analysis showed that the risk of developing new cavities declined by 12 percent among the children who received fluoride varnish,   compared with those who did not. And they added that fluoride varnish could still be a cost-effective alternative in some cases. However, they also stated, “This was a rather modest benefit, as a large number of the children developed new dentine caries lesions, regardless of fluoride varnish use.”

Concentrations of fluoride can also vary among different varnishes, Dr. Cunha-Cruz said.

That’s not to say that there aren’t highly effective topical treatment alternatives. Sealants do a good job of protecting the teeth, especially those hard-to-reach ones in the rear of the mouth, Dr. Cunha-Cruz said. Even better are sealants with glass ionomer, which releases fluoride, as opposed to resin-based sealants, which don’t have it.

Sealants are more difficult to apply than varnish, but Dr. Cunha-Cruz said that they remain effective for two to three years. Silver diamine fluoride has also been growing in popularity and is very effective in stopping decay, she said, but more research is needed on its preventive effect. It can also discolor teeth, but that isn’t as much of a concern for preschoolers who still haven’t lost their primary teeth.

“The evidence still supports the use of fluoride toothpaste, which is easy and low-cost,” Dr. Cunha-Cruz said. “The value of toothpaste lies in how it creates a daily presence of fluoride in the mouth.” Fluoride rinse is also effective in this way, she said.

For now, she and her research colleagues are calling for more studies of fluoride varnish’s cost-effectiveness among different populations and application settings.

Meanwhile, aside from using fluoride toothpaste and rinses each day, Dr. Cunha-Cruz suggests another approach: “Reducing sugar intake is an even more cost-effective strategy.”

Researcher Jeffrey McLean named to key review panel

Dr. Jeffrey McLean

Dr. Jeffrey McLean, an associate professor of periodontics at the School of Dentistry, has been named to a three-year term as a member of the Oral, Dental and Craniofacial Sciences Study Section at the Center for Scientific Review. The center is part of the National Institutes of Health (NIH).

Study sections review grant applications submitted to the NIH, make recommendations on these applications to the appropriate NIH national advisory council or board, and survey the status of research in their fields of science.

“These functions are of great value to medical and allied research in this country,” said Dr. Noni Byrnes, the center’s director, in a letter announcing the appointment.

Members are chosen based on their demonstrated competence and achievement in their scientific discipline as evidenced by the quality of research accomplishments, publications in scientific journals, and other significant scientific activities, achievements and honors.

Dr. McLean received his PhD at the University of Southern California and his MSc at the University of Guelph in Canada. Before coming to the University of Washington in 2014, Dr. McLean had worked as a researcher at the Pacific Northwest National Laboratory in Richland, Wash., and the J. Craig Venter Institute in La Jolla, Calif., a highly regarded center of genomic research.

Much of his work has focused on microbial interactions in oral biofilm communities. In 2014, he and his research colleagues published a groundbreaking study of microbial “dark matter,” or bacteria whose existence had been known but which defied efforts at cultivation.

A few months later, he and research colleagues at UCLA published a study showing how an engineered microbial peptide could kill the bacteria that cause tooth decay without harming the mouth’s beneficial bacteria.

This year, he and colleagues published a study in Proceedings of the National Academy of Sciences that showed how a larger genetic inventory may help explain how certain dangerous bacteria can persist in a hospital environment and continue to infect patients.

“There’s a huge number of bacteria we never know anything about,” he said in an article in the UW Dental Alumni News in the spring of 2017. “Three of these groups are in the oral cavity, and we’re working on cultivating and sequencing all of them in the body. We want to learn how they affect each other and our cells.”

Starvation study shows bacteria’s survival skills

A larger genetic inventory may help explain how certain dangerous bacteria can persist in a hospital environment and continue to infect patients, according to a new study in the journal Proceedings of the National Academy of Sciences.

In their paper published on Thursday, researchers including Dr. Jeffrey McLean of the UW School of Dentistry describe their discovery that three closely related species of bacteria of the family Enterobacteriaceae outlived all other oral bacteria in a long-term starvation or “doomsday” experiment.

“A number of species from that family are known to cause infections in hospitals,” said Dr. Xuesong He, an associate member of staff at the Forsyth Institute of Cambridge, Mass., and co-author of the study. Other team members were from the University of California, Los Angeles, and the J. Craig Venter Institute of La Jolla, Calif., and Rockville, Md.

More than 200 different bacterial species live inside your mouth. Some are highly abundant, while others are scarce. A few of these oral bacteria are known pathogens, which can cause disease. However, most are harmless or even beneficial.

Scientists know the genetic makeup of about 70% of oral bacteria. What they don’t know is which species would be most successful in surviving long-term starvation — so they decided to find out.

To create a battle of bacteria, researchers placed a community of oral bacteria, derived from human saliva, into a mixture of sterilized saliva and saline solution. The bacteria, which are accustomed to living in the nutrient-rich mouth, were starved in their new environment. Every few days, scientists checked the samples to see which bacteria were still alive.

Nearly every bacterial species died within the first couple of days. But three species — Klebsiella pneumoniae, Klebsiella oxytoca, and Providencia alcalifaciens — survived the longest, with K. pneumoniae and P. alcalifaciens surviving for more than 100 days.

Researchers were surprised to find that Klebsiella were among the champions of this bacterial combat. In the mouth, Klebsiella are considered an underdog, accounting for only about 0.1% of all microbes there. But in an extreme environment deprived of all nutrients, Klebsiella gained superiority, while the bacterial populations normally found in high abundance died off rapidly.

“When we look at the genome content, it turns out that these Enterobacteriaceae species have larger genomes than other oral bacteria, giving them the capacity to tap into more diverse energy sources,” said Dr. He.

To begin to understand how Klebsiella pulled off such a feat, scientists analyzed the genome of the bacteria on the first day of “battle” and then again on day 100. They found that the Klebsiella had undergone genetic mutations that may have allowed them to survive and continue to function, even without a food source.

“Oral fluids like saliva are a rich source of bacteria and viruses,” said Dr. McLean, another co-author of the study and an associate professor of periodontics at the School of Dentistry. “We want to understand how pathogens that are typically rare can become dominant and then also persist for long periods outside the body to be later transmitted.”

Scientists describe Klebsiella species as opportunistic pathogens. In healthy people, they live in the mouth peacefully, crowded by other microbes and are unable to grow or cause trouble. But outside the mouth, where few other oral bacteria survive, Klebsiella is king.

The species persists on hospital surfaces, like sinks or tables. Patient with compromised immune systems who contact the Klebsiella can develop infections that can lead to such dangerous conditions as pneumonia, meningitis, or septicemia. Pneumonia caused by Klebsiella has a very high death rate of around 50%. One reason why Klebsiella infections are so dangerous is that these bacteria are particularly adept at developing resistance to antibiotics, as well as transferring this drug resistance to their neighbors.

“The finding that these Klebsiella species survive longer than their more benign neighbors in mixtures of saliva is likely to have a great deal of clinical significance, as multiple virulent outbreaks of antibiotic-resistant Klebsiella have been traced back to hospital sinks and drains,” said Dr. Jonathon Baker. Dr. Baker is a Ruth L. Kirschstein NRSA Fellow at the J. Craig Venter Institute and lead author of the study.

The techniques employed in this research are key to illuminating the ecological dynamics of bacterial communities.

“From a big-picture point of view, this is a huge step forward toward understanding microbial social structure and ecology,” said Dr. Wenyuan Shi, CEO and chief scientific officer at the Forsyth Institute. “This study begins to address a fundamental question in biology: How, evolutionarily, was a microbial community built, and what takes place as the community dies?”

 

A color-coded view through the microscope shows part of the diverse bacterial population that flourishes inside the mouth.
A color-coded view through the microscope shows part of the diverse bacterial population that flourishes inside the mouth. Photo: Jessica Mark Welch and Gary Borisy, PNAS.1522149113

Laquita Grissett named Magnuson Scholar

Laquita M. Grissett, a PhD candidate at the School of Dentistry, has been named a University of Washington Magnuson Scholar for 2019-20, the university has announced.

Laquita GrissettGrissett, a graduate research assistant in the school’s Department of Oral Health Sciences, is one of the six scholarship recipients named annually, one for each of the UW’s Health Sciences schools. She plans to pursue a dental degree after completing her PhD.

“I feel incredibly blessed and honored to be a recipient of the Magnuson Scholarship,” she said. “This is an extremely prestigious award, and my heart is overflowing with gratitude.”

The scholarships, funded from a $2 million endowment from the Warren G. Magnuson Institute for Biomedical Research and Health Professions Training, commemorate the late U.S. Sen. Warren G. Magnuson. He was a dedicated supporter of biomedical research and was instrumental in establishing the National Institutes of Health, Medicare, and Medicaid during his career in the Senate. The awards are the highest given to UW Health Sciences students, who are selected for their academic performance and potential contributions to research in the health sciences.

Grissett’s current research at the Fred Hutchinson Cancer Research Center focuses on understanding the cellular and molecular underpinnings that govern and drive the development of head and neck squamous cell carcinoma in patients with a genetic disorder called Fanconi anemia. After she completes her studies, she said, she wants to pursue head and neck cancer research and investigate the link between oral and systemic diseases.

A South Carolina native, she received a BS in biology, magna cum laude, from the University of South Carolina in 2016 and was named to the Phi Beta Kappa honorary society. She was a 2017 National Science Foundation Graduate Research Fellowship Program pre-doctoral trainee, and her previous scholarship awards include a 2019 Student/Post-Doc Advisory Committee Course Scholarship at the Fred Hutchinson Cancer Research Center, Abney Foundation Scholarship, Benjamin A. Gilman International Scholarship, and University Studies Abroad Consortium Scholarship.

She has also been a volunteer in Washington at a migrant camp and at Seattle’s Danny Woo Community Garden, and was a mentor while completing the UW’s Summer Medical and Dental Education program. In South Carolina, she served at a retirement community and a food bank.

“I am so happy to learn that Ms. Grissett has been named a UW Magnuson Scholar this year,” said Interim Dean Gary Chiodo. “Her work in elucidating the molecular bases for head and neck cancer in Fanconi anemia patients is critically important and timely. While Fanconi anemia remains a relatively rare genetic disease, it carries very high morbidity and mortality. We have so much more to learn about it, and Laquita’s research focus is another important step toward improving diagnosis and treatment options.”

UW researcher promotes oral health in at-risk communities

Topical fluoride, dental visits, and a diet with little or no sugar are all effective tools to maintain healthy teeth. But how can you maintain dental health when families can’t – or won’t – make use of those tools?

Dr. Joana Cunha-Cruz
Dr. Joana Cunha-Cruz

In two studies set more than 2,000 miles apart, Dr. Joana Cunha-Cruz, a University of Washington researcher, is hoping to find answers. In Alaska, she’s working to help train dental providers to maximize their skills and improve the delivery of care. In Yakima, Wash., she’s working with dietitians to help families make a simple change: more water, fewer sugary drinks.

“Our thinking should be more in terms of population health,” says Dr. Cunha-Cruz, a member of the Department of Oral Health Sciences faculty at the UW School of Dentistry. With that mind-set, she’s looking for ways to reach out effectively to communities that have historically struggled with high levels of dental disease.

Working in a number of small, relatively isolated southeast Alaskan communities, she’s conducting a two-year project to train dentists and dental health aide therapists (DHATs) to improve the delivery of care. DHATs, who have two years of training and function in a way similar to physician assistants in medicine, can perform routine dental services and develop treatment plans. In Alaska, they’ve been employed since the early part of this century.

The dental providers face stark challenges. In the first two Alaskan communities involved in the project, about 50 percent of the children are in families below the federal poverty level. Along with that, there’s a lack of family resources which support healthful habits. Families also have limited access to healthy foods; fresh fruits and vegetables are expensive and don’t last long.

“The easiest food choices are usually processed foods and sweets,” Dr. Cunha-Cruz says – and that’s rocket fuel for decay-causing bacteria. “Water supplies often aren’t fluoridated, and with lots of poverty, oral hygiene is way down on the list of concerns.”

One issue with delivery of care, she says, is that it’s more effective if it’s culturally appropriate, so that’s a key focus of the project’s training program. She also wants to make treatment less intimidating and give more emphasis to early treatment and prevention.

“In the distant past, some care has been provided by dentists who travel by boat, mostly to perform extractions, so the dental experience has often been painful and traumatic,” she says. That leads dental providers to ask themselves, “How can I be the provider who promotes oral health instead of merely treating dental disease?” Working with the providers, Dr. Cunha-Cruz wants to join their efforts to shift the emphasis to wellness for the whole child and for communities.

In Yakima, Dr. Cunha-Cruz is collaborating with dentists and dietitians at the Yakima Valley Farm Workers clinic to change family habits relating to sugary drinks and juice. In the one-year pilot study, which started last month, they’ll work with 21 families. Cute animal-shaped water bottles containing fluoridated water will be delivered to the families’ homes.

“The big thing is to change the home environment,” Dr. Cunha-Cruz says. “We won’t be telling parents that juice is bad, but rather that they need to make water more available to their children. Then we’ll assess how well the parents are doing. We also want to facilitate self-evaluation, and see what the parents are doing to find solutions.”

The dietitians will use well-established behavioral techniques to help their families: setting up goals, giving positive reinforcement, finding solutions to problems. They’ll also track family members’ height and weight. After a brief initial meeting with the families, the dietitians check in by phone once a week for a month. After two months, the families return to the clinic for another meeting.

Some solutions may lie outside the home, too. In schools, for example, placing water fountains closer to cafeterias has helped cut down consumption of sugary drinks. Children might choose juice as a “healthful” alternative, but Dr. Cunha-Cruz cautions that this isn’t a good option.

“Most of the juice we get at the supermarket is high in added sugar,” she says.

UW helps HIV research put more focus on oral health

University of Washington researchers are helping to place oral health more squarely in the mainstream of HIV research, taking a major step during a symposium in Kenya’s Machakos County in February.

From left: Dr. Arthur Kemoli, Dr. Francisco Ramos-Gomez and Dr. Ana Lucia Seminario at the Inter-CFAR Sub-Saharan Africa Symposium.
From left: Dr. Arthur Kemoli, Dr. Francisco Ramos-Gomez and Dr. Ana Lucia Seminario at the Inter-CFAR Sub-Saharan Africa Symposium.

For the first time, oral health was incorporated into the Inter-CFAR Sub-Saharan Africa Symposium, which drew hundreds of researchers. They included Dr. Ana Lucia Seminario of the UW School of Dentistry, who lectured on current studies that aim to understand more about HIV’s effect on children’s oral health and quality of life.

Dr. Seminario is director of the School of Dentistry’s DeRouen Center for Global Oral Health, whose work includes extensive collaboration with Kenyan researchers including Dr. Arthur Kemoli of the University of Nairobi. Dr. Kemoli’s symposium presentation described his university’s work on oral health training and research.

The symposium, sponsored by the UW/Fred Hutch Center for AIDS Research (CFAR) and the National Institutes of Health, also drew researchers including:

  • Caroline Shiboski, chair of the Department of Orofacial Sciences at the University of California San Francisco, who delivered a presentation on “Oral Diagnostic Tool for Non-Dentists: Evolution of Inter-Professional Collaborations to Advance HIV-Related Global Oral Health Research.”
  • Francisco Ramos-Gomez, director of the UCLA Center for Children’s Oral Health and director of UCLA’s Pediatric Dentistry Advanced Clinical Training Program, who lectured on “Oral Manifestations of HIV in Children.”

A CFAR-Sub-Saharan Africa working group is striving to promote new research collaborations by its members directed at high-priority scientific and public health challenges. The group also seeks to mentor young Sub-Saharan Africa research investigators.

UW-led research team discovers tooth loss predictor

A team led by University of Washington researchers has uncovered what appears to be the first metabolic predictor of tooth loss.

Shots of young and old dental pulp stem cells, both rapidly aging and slowly aging, show a marked difference.
Shots of young and old dental pulp stem cells, both rapidly aging and slowly aging, show a marked difference.

The researchers found important clues about stem cell metabolism that shed new light on the ability of teeth to repair themselves. Their study, published Feb. 18 in the British journal Scientific Reports, found a link between the metabolic activity of dental pulp stem cells (DPSCs) and the speed at which they age. As cells age, they become less able to regenerate themselves. The loss of this ability, in turn, can spell the earlier loss of teeth.

In particular, the researchers found that slower-aging DPSCs showed a strong capacity to use fats as a fuel source to create the energy needed for regeneration and other cellular processes. The researchers also found that the metabolic differences between fast- and slow-aging cells could be identified even before the onset of aging. This, they believe, suggests that metabolic activity serves as an early indicator of DPSC aging and can predict the cells’ ability to regenerate.

Dr. Hannele Ruohola-Baker
Dr. Hannele Ruohola-Baker

The paper’s lead authors were Dr. Hannele Ruohola-Baker and Dr. Ammar Alghadeer. Dr. Ruohola-Baker holds UW appointments in the School of Dentistry, the School of Medicine’s Department of Biochemistry and the Institute for Stem Cell and Regenerative Medicine, and Department of Bioengineering.  Dr. Alghadeer is a graduate student in the School of Dentistry’s Department of Oral Health Sciences. Yan Ting (Blair) Zhao, another Oral Health Sciences graduate student, was third author of the paper.

“These findings are important for future regenerative dentistry,” Dr. Ruohola-Baker said. This rapidly evolving field of study, related to tissue engineering, focuses on therapies to replace failing stem cells to revitalize the tooth pulp.

Dr. Ammar Alghadeer
Dr. Ammar Alghadeer

“Resident adult dental stem cells are known to participate in tooth regeneration and repair that follows injury,” Dr. Ruohola-Baker said. “Aging impedes this essential regeneration capacity of human adult stem cells. Understanding and combating aging is a grand challenge in modern biology.”

In addition to these, other research entities represented on the team include the SRM Institute of Science and Technology in Chennai, India; the College of Dentistry at Imam Abdulrahman bin Faisal University in Dammam, Saudi Arabia; the UW Department of Pharmacology; the UW Department of Comparative Medicine; Covance Genomics Laboratory in Redmond, Wash.; and the UW’s Paul G. Allen School of Computer Science and Engineering.

Yan-Ting (Blair) Zhao
Yan-Ting (Blair) Zhao

“This study is an excellent example of the importance of collaboration across disciplines in the life and clinical sciences, in this case between dentistry, stem cell biology and developmental biology,” said Dr. Richard Presland, associate professor and graduate program director in the UW Department of Oral Health Sciences.

Dental students display their research prowess

Claire Mills
Claire Mills

Pre-doctoral and graduate dental students exhibited poster presentations of their research in diverse fields ranging from histology to oral biology to materials science at the School of Dentistry’s 24th annual Research Day on Monday.

Philip Walczak
Philip Walczak
Nousha Panahpour Eslami
Nousha Panahpour Eslami

Second-year student Claire Mills won first place in the pre-doctoral student competition for a project titled “Low Molecular Weight Hyaluronan Increases Human Periodontal Ligament Cell Motility,” mentored by Dr. Tracy Popowics. She will represent the school at the national Dentsply/Sirona Student Clinician Competition at the annual meeting of the American Association for Dental Research (AADR) in June.

Her classmate Philip Walczak took second place for research titled “Pilot Clinical Testing of a Fluorescence-Based Intraoral pH Measurement Device,” mentored by Dr. Eric Seibel and Dr. Ali Sadr. He will represent the school at the Dentsply/Sirona competition in 2020.

Another classmate, Nousha Panahpour Eslami, won third place for her project titled “Can Silver Diamine Fluoride and Glass Ionomer Remineralize Natural Dentin Caries?” She was mentored by Dr. Sadr.

Ana Chang, a PhD candidate in the Department of Oral Health Sciences, won the graduate student competition for her presentation titled “Toll-like-receptor-2 and -4 Responses Regulate Neutrophil Infiltration into the Junctional Epithelium.” She was mentored by Dr. Richard Darveau, and will receive free registration and travel funds for the 2019 AADR meeting.

Dr. Cecilia Giachelli, professor and chair of the UW Department of Bioengineering, kicked off the day with a keynote talk titled “Building Bridges,” exploring research collaborations between her department and the School of Dentistry.

Dr. Cecilia Giachelli
Dr. Cecilia Giachelli

She cited a significant clinical need for advanced methods of bone regeneration in dental and craniofacial practice, and discussed two particular collaborations. One centers on the use of fibrinogen, a protein in the blood that produces fibrin, another protein that forms a fibrous mesh that can serve as tissue scaffolding. This scaffolding can be infused with BMP (bone morphogenetic proteins), a bone regeneration agent.

Dr. Giachelli also discussed a research project involving bone cells known as osteoclasts, which absorb bone tissue during growth and healing. The UW is researching bioengineered osteoclasts to remedy a deficiency of these cells arising from a condition known as medication-related osteonecrosis of the jaw (MRONJ). A side effect of drugs used in cancer treatment, MRONJ leads to progressive bone loss.

The UW researchers are still analyzing their results, Dr. Giachelli said, but the research so far is  promising.

Other speakers during the day’s morning session included:

  • Dwayne Arola, associate professor in the Department of Materials Science and Engineering, who addressed “Aging of Teeth and Its Importance to Dental Practice.”
  • Douglas Ramsay, professor and chair of the Department of Oral Health Sciences, who discussed “Mouthguards and the Orthodontic Patient.”
  • Eric Seibel, research professor in the Department of Mechanical Engineering, who spoke about “New Optical Dental Care – From Caries Prediction to Therapy Monitoring.”

UW researchers help take major step in study of elusive bacteria

Two University of Washington researchers and their colleagues have helped take a significant step forward in the study of especially tiny bacteria that may be linked to gum disease.

Dr. Jeffrey McLean
Dr. Jeffrey McLean

Dr. Jeffrey McLean and Dr. Thao (Jenny) To of the UW School of Dentistry and their cohorts at the Forsyth Institute in Cambridge, Mass., have been studying a group of microbes known as TM7, which is considered microbial “dark matter.” This term alludes to the extreme difficulty such bacteria have posed to researchers trying to cultivate them in the lab. Dr. McLean is Associate Professor of Periodontics at the UW and Dr. To is a senior postdoctoral fellow in his lab.

TM7 is found in a number of environments, including the mouth, and may play a role in gum disease, scientists believe. In 2015, Dr. Xuesong He of Forsyth and Dr. McLean co-wrote and published a paper telling how they had cultured TM7 for the first time in a test tube and sequenced the complete genome. They discovered that it is an ultra-small bacterial parasite with a tiny genome that lives and feeds on other bacteria, which makes it difficult to isolate and examine. This was considered a major step toward understanding the human oral microbiome, or the collection of bacteria that live in the mouth.

Now, in a paper published recently in the journal Proceedings of the National Academy of SciencesDr. Batbileg Bor, a senior postdoctoral fellow in microbiology at Forsyth, said that he and the team have been able to isolate TM7 bacteria from their host and count them individually, and then add the bacteria back to their host cultures.

This has allowed the researchers to see not only how TM7 infects and parasitizes its hosts, but also to uncover the mechanism TM7 uses to establish a long-term parasitic relationship with those hosts. The finding may also explain why TM7 bacteria persist for so long in the human mouth.

The system the researchers developed could be used to study other types of ultra-small bacteria, as well, Dr. He said. TM7 is still relatively new to scientists, and it took Dr. Bor nearly three years to develop the new method of studying it.

“We are continuing to learn about how this TM7 species and other ultra-small bacteria like them are able to survive and find other cells to live on, since they are in found in every human body and increase in number within certain oral diseases,” Dr. McLean said.

Other collaborators on the study included Drs. Wenyuan Shi, Floyd E. Dewhirst, and Lujia Cen from the Forsyth Institute, and Kevin R. Foster from the University of Oxford.

Researcher: Public misled on brushing teeth

Almost any schoolchild can tell you: We prevent cavities by brushing our teeth, because that’s how you remove the sticky film containing millions of decay-causing germs.

Dr. Philippe Hujoel
Dr. Philippe Hujoel

But this notion is more of an advertising-created myth than fact, says Dr. Philippe Hujoel, a School of Dentistry researcher, in an article published in the journal Gerodontology.

Almost as far back as a century ago, scientists regarded oral hygiene products as useless in preventing dental cavities.  The bacteria causing cavities had been documented to dwell in fissures and cracks on teeth, where they were inaccessible to oral hygiene products.  Subsequent clinical research confirms that these scientists had it right. That raises the question: How could dental plaque removal become considered a first line of defense in dental cavity prevention?

In his journal article, Dr. Hujoel cites direct-to-consumer advertising in the early 20th century, which turned the idea that simple oral hygiene could remove the cavity-causing film into accepted wisdom. The man who globalized this myth to sell toothpaste was marketing pioneer Claude Hopkins.

Hopkins also engaged in fearmongering, including claims that grave diseases would be prevented when buying the toothpaste he advertised.

Leading scientists, scientific councils, and ethical toothpaste manufacturers did their best to dispel the myths created by such misleading advertising. William Gies, a founder of modern dental education, criticized the scientific ignorance of Hopkins’ advertisements. Scientific councils declared that oral hygiene products were cosmetics. And one ethical oral hygiene company’s advertisements described  how pseudo-scientific claims created an epidemic of misconceptions.

However, none of these efforts prevailed against the power of Hopkins’ mass marketing.

On the contrary, advertising directly to health professionals bolstered the perceived effectiveness of oral hygiene products in preventing dental decay, Dr. Hujoel says in the Gerodontology article. Such advertising is now recognized as effective in increasing sales – and as compromising professional organizations in their public health advice.

The later discovery of fluoride as an effective anti-cavity agent further confounded the common wisdom on how to prevent cavities. People often attributed the benefits of fluoride toothpaste to the associated oral hygiene, an idea unsupported by a large body of clinical trial evidence, Dr. Hujoel says.

In addition to fluoride’s effectiveness, Dr. Hujoel says that what the evidence has actually shown for decades is the importance of vitamin D, which plays a key role in mineralizing and strengthening teeth. Yet vitamin D has now virtually disappeared from the popular discussion of preventing dental decay.

If decades of advertising have skewed popular thought on how to prevent cavities, what should consumers do? Dr. Hujoel suggests not to look for oral health guidance in advertising. Diet is key – people on very low carbohydrate diets don’t have to worry about cavities, he says, while those who eat significant amounts of sugars and starches should use a toothpaste or oral rinse with fluoride.

Study shows how austerity devastated Greece’s health

A new study by a School of Dentistry faculty member and dozens of other researchers from the University of Washington and around the world has found that Greece’s population health declined markedly and death rates rose sharply after harsh austerity measures were imposed on Greece by the European Union and the International Money Fund in 2010.

Gergios Kotsakis
Dr. Georgios Kotsakis

“This study is important because it provides a framework for health surveillance on a national level following major socioeconomic changes,” said Dr. Georgios Kotsakis of the School of Dentistry’s Department of Periodontics, one of the study’s authors.

The study, which was published this week in the British journal The Lancet Public Health, reported that government health spending fell sharply and that the causes of death that increased the most were largely those that could have been addressed by health care. The researchers noted that Greece’s reduced health spending, required as part of the austerity measures, had been criticized for omitting measures to protect the country’s National Health System. They said that health policymakers should place a special focus on ensuring that Greece’s health-care system is equipped to meet the needs of the country’s citizens.

The study, which was funded by the Bill & Melinda Gates Foundation, relies heavily on the UW’s 2016 Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). The 2016 GBD study, conducted by the UW’s Institute for Health Metrics and Evaluation (IHME), is an outgrowth of the original 1997 GBD study. This was the world’s largest systematic effort to chart the scope of health loss from all major diseases, injuries, and risk factors by age, sex, and population.

Co-authors of the Greece study were Dr. Kotsakis, assistant professor at the School of Dentistry;  Dr. Stefanos Tyrovolas, a visiting scholar at the School of Dentistry; Dr. Andy Stergachis, professor of pharmacy and global health and associate dean at the UW School of Pharmacy; and Dr. Nick Kassebaum, associate professor at IHME and in the Department of Anesthesiology and Pain Medicine at Seattle Children’s Hospital. The four were joined by 43 other GBD collaborators in a number of countries, including 15 at the UW.

Greek Flag against sky
The harsh austerity measures imposed on Greece prompted widespread protests. Photo: CNN

The researchers identified an increase in the pace at which Greece’s population was aging as another important concern and wrote: “The increase in total deaths in children younger than 5 years and older adults with increase in causes sensitive to resource availability (e.g., access to screening and urgent care) suggest that the health system requires substantial restructuring to cope with the effects that the financial crisis has had on resource availability, resource allocation, and population structure.”

They reported that while the country’s overall death rate rose by about 5.6 percent from 2000 to 2010, it jumped by about 17.7 percent in the six years that followed, after austerity measures were imposed. The rate rose three times faster than the rate in Western Europe overall, and came at a time when mortality rates were actually declining worldwide. The largest increase came among people 70 and older, while the very young also saw a disproportionate increase.

The rise in mortality coincided with changes in causes of death, with notable increases in communicable, maternal, neonatal, and nutritional diseases.

Other findings from the study included these:

  • The incidence of tuberculosis increased among native-born Greeks after austerity was imposed.
  • The incidence of HIV nearly doubled from 2010 to 2012, spurring reinstatement of syringe distribution programs. After this was done, HIV rates declined.
  • The period of austerity saw rises in major depression and suicide, as well as a lack of improvement in in maternal, infant, and child mortality rates.

“Notably, the number of individuals with unmet health-care needs nearly doubled since 2010, with a considerable fraction reporting health-care cost as the main reason for not receiving the recommended health-care services,” the researchers wrote.

School remains No. 3 in world in research rankings

The University of Washington School of Dentistry retained its No. 3 global and U.S. ranking in the newly released 2018 Academic Ranking of World Universities (ARWU) by the ShanghaiRanking Consultancy.

Dr. Baldwin at Computer with skull
Dr. Michael Baldwin, who received his DDS from the UW in 2015, is studying for his PhD in oral biology in the school’s DDS-PhD program, which is one of the School of Dentistry’s key research tracks for students. This year, Dr. Baldwin was also named a UW Magnuson Scholar, one of the UW’s highest academic awards.

The rankings, which are weighted toward research performance and reputation, place the school behind only the dental schools of the University of Michigan and the University of North Carolina. Harvard University and King’s College London complete the top five in the category of dentistry and oral sciences. The annual rankings were originated by Shanghai Jiao Tong University in 2003.

Dr. Sara Gordon, the school’s associate dean of academic affairs, expressed pride in the school’s ranking and said: “Our faculty engage in compelling research within the school, and with partners in the university and around the globe. Pre-doctoral students can choose a research track that trains them in requisite skills, then places them in faculty labs, where they can complete a research project.”

Earlier this year, the school placed fourth in the United States and 14th in the world in the annual Quacquarelli Symonds (QS) World University Rankings assessment of dental schools. The British educational organization’s ratings also take research into account, but are a broader assessment than ARWU.

Dr. Gordon cited the school’s curriculum, which has been extensively revised in the last several years, as one reason for its standing.

“Our faculty members and staff have worked very hard over recent years to thoroughly revamp the curriculum,” she said. “The school aims to lead the world in producing dental graduates who are not only technically excellent but also have enhanced medical, interprofessional, and critical thinking skills necessary for the changing world of dentistry. We have an integrated systems-based biomedical foundations curriculum, a third-year clerkship skills program, and a comprehensive-care fourth-year program.”

The clerkship program takes third-year students through a series of six-week and 12-week clinical rotations designed to provide a more intensive exposure to the core skills of general dentistry. The fourth-year clinical program seeks to duplicate the wide-ranging experience of general dental practice.

School officials have cited the national dental board examinations as one indicator of the new curriculum’s value. In 2017 and 2018, the school’s fourth-year students recorded aggregate scores on the clinical proficiency portion of the exam that placed them in the nation’s top two or three classes.

Dr. Gordon also said: “The school has a strong emphasis on social responsibility, locally and as a partner in global health initiatives. All pre-doctoral students serve in community clinics for periods ranging from five weeks to five months.”

UW oral health center wins grant for Africa HIV research

The University of Washington’s Timothy A. DeRouen Center for Global Oral Health has received a grant to support research on African children and adolescents exposed to the human immunodeficiency virus (HIV).

Large group of Kenyan children
Kenyan schoolchildren receive oral hygiene instruction. (Photo courtesy of Dr. Arthur Kemoli, University of Nairobi)

The center received a 2018 Regional Development Grant from the International Association for Dental Research (IADR), and will share it with IADR’s Nigeria division and East and Southern Africa divisions. The grant will be used to create a sustainable research site to support the

AFRICA Project (Advocating For HIV Research In Children and Adolescents).

As part of the grant, junior faculty from Nigeria and Kenya will attend the UW School of Dentistry’s Summer Institute in Clinical Dental Research Methods and also study HIV in the UW School of Public Health. This funding enhances DeRouen Center’s existing collaboration with Kenya and expands its African outreach to Nigeria.

A strategic planning meeting is scheduled in late July at the 2018 IADR annual meeting in London with grant co-investigators Dr. Morenike Folayan of Nigeria’s Obafemi Awolowo University, Dr. Arthur Kemoli of Kenya’s University of Nairobi, and their IADR division leadership.

Dr. Kemoli will also talk at the DeRouen Center’s first symposium on global oral health in Seattle on July 31. More information on the Center’s work in Kenya can be found on the Center’s website.

Dentistry PhD candidate receives major grant to study oral pain syndrome

Dr. Sumeia Werfalli, who is studying for her PhD in oral biology at the School of Dentistry, has been awarded a Scan│Design Foundation Innovative Pain Research Grant by the University of Washington Department of Anesthesiology & Pain Medicine.

Dr. Sumeia Werfalli head shotDr. Werfalli, who already holds a dental degree from Libya’s Benghazi University dental school and earned her master’s degree in dentistry after completing a residency in oral medicine at the UW in 2013, will use the $41,290 grant to support her studies of salivary mucins in patients with burning mouth syndrome.

Mucins are proteins that make up the primary components of mucus, and they help lubricate and protect the oral cavity. Burning mouth syndrome, as its name implies, is a burning sensation that usually occurs on the tip of the tongue or roof of the mouth, but can also appear elsewhere in the mouth. The condition affects primarily postmenopausal women and is commonly associated with dry mouth.

“The impact of this condition on the quality of life of these sufferers is substantial,” Dr. Werfalli said.  It has no well-identified cause, and can last for years. Treatment options are scarce.

Dr. Werfalli’s study will explore the hypothesis that the syndrome is caused by a mucin-related malfunction of the oral epithelial barrier, the layer of tissue that provides the mouth’s first line of defense against bacteria and other threats. She believes that her findings may also help shed light on other pain conditions such as irritable bowel syndrome.

She will be the principal investigator on the Scan│Design Foundation study, and her co-investigators will include her mentor, Dr. Linda LeResche, Associate Dean of Research for the School of Dentistry; Dr. Jill Johnson, Associate Professor in the Department of Hematology in the UW School of Medicine; Dr. Mark Drangsholt, Chair of the Department of Oral Medicine at the School of Dentistry; Dr. Richard Presland, Oral Health Sciences graduate program director at the School of Dentistry; and Dr. Susanne Kölare Jeffrey, a member of the Oral Health Sciences faculty.

“I am very honored and grateful for receiving this significant award, which motivates me to complete my research project as well as additional assays in support of my dissertation work,” Dr. Werfalli said.

The nonprofit Scan│Design Foundation, established in Denmark and Seattle in 2002, supports pain research. It is funded by Scan│Design Furniture, which opened in Bellevue in 1964 and now has stores in Washington and Oregon.

UW researchers find no-drill way to heal cavities

Tooth schematic of healing peptides
A University of Washington research team that includes School of Dentistry faculty members has designed a natural product using engineered proteins called peptides to rebuild tooth enamel and heal cavities in their early stages.

The peptide product actually adds new layers to tooth enamel in a process called remineralization. It can be used in toothpaste, gels, or other forms. And while fluoride toothpastes and mouthwashes strengthen existing tooth enamel, they do not actually add any to the tooth.

The team’s findings were published in the journal ACS Biomaterials Science and Engineering. The team is led by Dr. Mehmet Sarikaya, professor of materials science and engineering and adjunct professor in the Department of Chemical Engineering and Department of Oral Health Sciences. Other journal co-authors include Dr. Greg Huang, chair of the School of Dentistry’s Department of Orthodontics, and Dr. Sami Dogan of the School of Dentistry’s Department of Restorative Dentistry.  Read more about the new peptide product.

UW global oral health symposium set for July 31

Registration has opened for a University of Washington national symposium on global oral health scheduled for July 31.

The symposium, titled “Inter-professional Collaboration in Healthcare: Adding the Oral Health Component to Successful Projects Worldwide,” will be hosted by the UW School of Dentistry’s Timothy A. DeRouen Center for Global Oral Health. It will feature lectures by five speakers:

  • Waranuch Pitiphat, DDS, PhD (Khon Kaen University, Thailand): “Faculty Development: The Impact of National Institutes of Health Funding on the Training of Thai Research Leaders.”
  • Jorge Luis Castillo, DDS, PhD (Universidad Peruana Cayetano Heredia, Peru): “From the Andes to the Amazon: Connecting the Peruvian Oral Research Community to the National Institutes of Health.”
  • Arthur Kemoli, BDS, PhD (University of Nairobi, Kenya): “Advocating for HIV Research In Children and Adolescents: The AFRICA Project.”
  • Joseph Zunt, MD, MPH (University of Washington/Fred Hutch Center for AIDS Research): “Oral Health Is Relevant to Global Health: Existing Opportunities Through Fogarty Fellows and Scholars.”
  • Florencia Vasta, Associate Program Officer, Bill & Melinda Gates Foundation: Nutrition, Global Development Program: “Investing in nutrition is investing in global health”

The DeRouen Center was established in 2013 to promote international collaborations in dental research and education. Its current collaborations include projects in Thailand, Peru, and Kenya, as well as in Seattle.

To register for the symposium, go here.

Oral health research center renamed

The Center for Global Oral Health, established at the School of Dentistry in 2013 to promote international collaborations in dental research and education, has been renamed to honor its founder, Dr. Timothy A. DeRouen.

The Timothy A. DeRouen Center for Global Oral Health is also refining its mission to align more closely with the University of Washington’s groundbreaking Population Health initiative.

Dr. DeRouen, Professor of Oral Health Sciences in the School of Dentistry and Professor of Biostatistics and Global Health in the School of Public Health, was the School of Dentistry’s Executive Associate Dean for Research and Academic Affairs in 2003-2011 and Interim Dean in 2011-2012. He also served as President of the American Association for Dental Research (AADR) in 2014.

Dr. Johnson and Dr. DeRouen shaking hands
Dr. James Johnson, Interim Dean of the School of Dentistry, congratulates Dr. Timothy DeRouen, board chair of the newly renamed Timothy A. DeRouen Center for Global Oral Health.

He has had a wide-ranging impact on oral health research through the Summer Institute in Clinical Dental Research Methods, which he founded in 1992 and which has trained approximately 600 researchers from more than 50 countries, along with more than half the states in this country.

Dr. Ana Lucia Seminario, Assistant Professor of Pediatric Dentistry and a member of the Global Health adjunct faculty at the UW School of Public Health, now directs the Center, while Dr. DeRouen chairs its board.

“One of our goals is to add an oral health component within ongoing UW projects worldwide,” said Dr. Seminario, who is an active researcher. While no new School of Dentistry operating funds have been directed to the renamed center, it will use existing funding, including grants, to pursue major collaborations with partners in Kenya, Peru, and Thailand. The first two countries were selected as the most promising new sites for oral health-related UW Global Health projects, she said.

More details are available on the Timothy A. DeRouen Center for Global Oral Health’s website.

New study reports benefits of dental therapists’ care

In the first long-term study of dental therapist utilization, University of Washington researchers have found that greater access to the therapists’ services in Alaska resulted in more use of preventive dental services and fewer extractions among adults and children. In addition, fewer children with more access required extractions of their four front teeth.

Dr, Donald ChiResearchers led by Dr. Donald Chi of the School of Dentistry analyzed 10 years of electronic health records and Medicaid claims data (from 2006 through 2015) for residents of Alaska’s Yukon Kuskokwim Delta communities.

The electronic health records also showed that higher availability of dental therapists was significantly linked to a lower incidence of children having dental care under general anesthesia, which is usually related to extensive dental work. Medicaid records, however, did not show a similar correlation.

“There appear to be clinically meaningful differences between communities with no dental therapists and communities with the highest number of dental therapist treatment days,” the report concluded.

“Our study shows that in a relatively short time period, dental therapists have made a difference,” Dr. Chi said. “Dental therapists in Alaska Native communities were associated with significantly higher rates of preventive care use and lower rates of extraction – for both children and adults. These findings should be of great interest to lawmakers who support evidence-based policymaking.”

Dental therapist with patient
A dental therapist works on a patient in southeast Alaska.

These dental providers, also known as dental health aide therapists (DHATs) or midlevel providers, have been employed in New Zealand and other countries for nearly a century. They receive basic dental training, but unlike dental hygienists, they can perform irreversible procedures such as extractions and fillings. In the Yukon Kuskokwim Delta, where the therapists were first deployed in 2006, they are recruited from local communities and work under the supervision of licensed dentists.

Alaskans face two major challenges in oral health. Not only does much of the population, especially Alaska Natives, have a significantly greater incidence of dental disease, but access to dental care can be severely limited in the state’s interior.

“Tooth decay is major public health problem in the United States,”Dr. Chi said. “Children go to bed with unresolved toothaches and they miss school because of the pain. Adults have trouble finding work because of missing teeth. Poor oral health perpetuates the cycle of poverty. Dental therapists are a starting point in addressing the consequences of dental disease and solving oral health inequalities in communities that lack dental providers.”

Dr. Chi noted that the study does have some limitations, noting that it was only observational and could not draw conclusions about cause and effect. “We did not assess unmet dental care needs, disease prevention, and quality of life,” the study also noted.

“Dental care use is not a panacea,” the study also cautions. “This underscores the importance of other behaviors relevant in oral health such as limiting sugar intake, optimizing fluoride exposure, and tobacco cessation.”

The study recommends that future research examine how extensively the Alaskan Native dental care network helps patients with strategies for behavioral changes and how their behavior and habits are influenced by dental therapists.

“This is especially relevant in in the Yukon Kuskokwim Delta, in which dental therapists maintain familial ties, share a common history, and understand the strengths and challenges as experienced by local populations,” the study says. “The eventual goal would be to harness the dental care delivery system as a way to improve oral health behaviors among individuals and norms within families and communities.”

The study is under review for publication by the PLOS ONE journal.

School is 3rd in world in research ranking

The University of Washington School of Dentistry is rated third in the world and the United States in the latest Academic Ranking of World Universities (ARWU), which is heavily weighted toward research performance and reputation.

Jon An in the lab
Dr. Jonathan An, an award-winning researcher who holds a DDS from the School of Dentistry and is now pursuing a PhD in oral biology, works in his laboratory.

In the rankings, compiled by the Shanghai Ranking Consultancy, the school trails only the dental schools of the University of Michigan and the University of North Carolina, with Harvard University and the University of California at Los Angeles rounding out the top five. The annual rankings were originated by  Shanghai Jiao Tong University in 2003.

The ARWU evaluation comes on the heels of the school’s No. 5 U.S. ranking and No. 14 world ranking in this year’s Quacquarelli Symonds (QS) World University Rankings. While the QS rankings also look closely at research, they are a broader assessment than ARWU.

QS placed the University of Hong Kong dental school first in the world, while the University of Michigan was first in the United States and No. 2 in the world. The other U.S. dental schools that QS ranked in the world’s top 15 were Harvard University, New York University and the University of North Carolina at Chapel Hill, in that order.

QS, a prominent British educational organization, assigned ranking scores based on academic reputation, employer reputation, and research citations per paper, plus an index measuring the productivity and impact of researchers’ published work. Survey participants also identified up to 10 domestic and 30 international institutions they considered excellent.

During the last few years, the UW School of Dentistry has phased in a new curriculum that incorporates changes in dental science and technology, new modes of dental practice, biomedical advances and more. In 2015, the school launched a series of third-year clinical “clerkship” rotations that give students a more intensive exposure to the core skills of general dentistry and significantly more repetitions of dental procedures.

In 2016, the school launched its Fourth-Year General Practice Clinic, which seeks to duplicate the experience of private practice as closely as possible. Fourth-year students also travel around Washington for five-week community clinic rotations that help improve their proficiency.

As a result of the curricular changes, the school has been singled out as a national leader in curriculum innovation for the last two years by the American Dental Education Association (ADEA). This year, the school also received the William J. Gies Award for Vision by an Academic Dental Institution, ADEA’s  highest recognition.

The award was bestowed for the Regional Initiatives in Dental Education (RIDE) program, which is designed to channel dental graduates to Washington’s rural and underserved areas. Students spend their first year at the RIDE facility on Eastern Washington University’s Spokane campus, return to Seattle for their second and third year, then serve extended community clinical rotations in their fourth year. Since the program began in 2008, about 70 percent of its graduates have gone on to practice in those rural and underserved areas.

Dr. Travis Nelson’s autism study featured in ADA journal

Dr. Travis Nelson of the UW Center for Pediatric Dentistry is the lead author of a study on treating children with autism that is the cover article in the July issue of the Journal of the American Dental Association.

Dr. Nelson examines child's mouth
Dr. Travis Nelson treats a young patient at the Center for Pediatric Dentistry’s autism clinic.

Dr. Nelson’s study discusses desensitization techniques, such as repeated visits, that could help many children with autism spectrum disorder. For the last several years, he has directed an autism clinic at the Center for Pediatric Dentistry that has enjoyed notable success in providing dental care to these children.

The behavioral issues of autism make it less likely for children with the condition to receive dental care than their typically developing peers, Dr. Nelson says. However, when children with autism were given the chance to practice dental skills at their own pace, most of the patients in the study were able to sit for an exam with a dental mirror, he says.

More than 75 percent of the children with autism in the study were able to undergo an exam in one to two dental visits, and nearly 90 percent were able to receive an exam within five visits with desensitization protocols, according to the study.

“The protocols we used are very simple and could be implemented elsewhere to help children with autism access needed dental services,” Dr. Nelson said.

State health official prescribes steps to fight opioid crisis

A leading Washington state health official on Tuesday urged medical and dental providers at a UW dental research forum to support more stringent prescribing guidelines and other measures to address the opioid abuse crisis.

Dr. Gary Franklin at podium
Dr. Gary Franklin discusses the opioid abuse epidemic during his keynote speech at the School of Dentistry’s Research Day.

Dr. Gary Franklin, medical director of the state’s Department of Labor and Industries, called it “the worst man-made epidemic in medical history,” citing more than 200,000 deaths and hundreds of thousands more overdose cases.

Franklin, who is also a research professor in the UW’s School of Medicine and in the Department of Environmental and Occupational Health Sciences, said the state has been a national leader in addressing the problem, but that other steps must be taken, especially in states with more permissive prescribing regulations.

“This was the saddest thing I’d ever seen,” he said as he discussed the problem at the School of Dentistry’s annual Research Day at the HUB, where he was keynote speaker. “Imagine that: You come into the system with a low backache, and you die?”

Along with repeal of permissive laws on opioid use, he called for states to adopt the Centers for Disease Control and Prevention’s tougher guidelines for prescribing opioids, and leveraging the power of large public health-care purchasing programs such as Medicaid.

Franklin also called on providers to protect children and teenagers by limiting initial opioid prescriptions to a maximum of three days or 10 tablets and employing only short-acting opioids for acute use. After that, he suggested, providers should either stop such medication or, if it was still deemed absolutely necessary, require patients to sign an informed consent so they would be fully aware of the medication’s risks.

In addition, he also suggested ways to improve the medical system’s capacity to treat pain and addiction:

  • Optimizing overdose case management
  • Employing behavioral therapy or graded exercises to help patients manage pain
  • Using medication-assisted treatment for patients with opioid use disorder
  • Improving patient access to expert advice on pain and addiction through resources along the lines of the UW’s TelePain, a weekly audio and videoconference consulting service for medical providers

“This is an emergency, and it’s going to take a huge effort in [the dental community] and in our state to reverse this thing,” he said.

Franklin noted the difficulty of tackling the crisis, starting with this: “There’s a problem treating pain. Doctors don’t have a lot of alternatives.” However, he also noted that while opioids have unmatched effectiveness in treating severe acute pain, studies show that they fare no better than less powerful and non-addictive drugs such as NSAIDs and acetaminophen in treating long-term pain.

Opioids, he said, should not be used routinely to treat conditions such as musculoskeletal pain, neuralgia or fibromyalgia.

He said that opioid users not only face a high risk of addiction and dependency, but develop rising tolerance for their pain-relieving effects. At the same time, they don’t develop a similar tolerance for the drugs’ depressant effect on the respiratory system, which is why respiratory failure is the usual cause of death by opioid overdose.

In the course of tightening regulation of opioid use, Washington state saw a 44 percent decline in deaths from unintentional prescribed opioid use from 1995 to 2015 – the largest such decline in the United States, he said.

Yet even as the state has reduced opioid-related deaths, he said, there has been a continuing spike in heroin-related deaths, mostly among people ages 18 to 30. The majority of opioid-related deaths have come among people ages 35 to 55.

Also troubling, he said, was a 2015 study that linked legitimate opioid use during high school – often for sports injuries – to a 33 percent increase in the risk of opioid misuse after graduation.

UW to host national saliva symposium

Imagine a future in which ailments such as heart disease or diabetes can be routinely detected with something as simple as a mouth swab.

David Wong
Dr. David T.W. Wong

In fact, that future is not far off, and saliva researchers are bringing it closer every day. And from Dec. 4 through 6, some of the field’s leading figures will gather at the University of Washington to discuss their work during the second annual North American Saliva Symposium.

“Saliva is one of the most undervalued components of our body,” said Dean Joel Berg of the School of Dentistry. “It cleans the mouth and the teeth, helps prevent diseases, and separately serves as marker which can signal the presence or onset of systemic disease.”

Dr. Berg’s own research includes studies of saliva as a carrier of oral biofilm and the relative content of various disease-causing bacteria in saliva.

John-McDevitt
John McDevitt

“There is new and exciting work which will make the use of salivary diagnostics routine to detect the status of diabetes, heart disease, and other chronic diseases,” he said.

Salivary diagnostics have any number of advantages, the American Dental Association (ADA) notes: ease of access, noninvasive sample-taking, and reduced risks of infectious disease transmission. For patients – especially children – who fear needles, the use of saliva promises a fast, painless method of testing. In addition, the use of saliva can reduce the cost of testing, which can also be conducted in non-traditional settings.

One previous drawback has been that the substances being measured, such as proteins or nucleic acid components, are found in lower concentrations in saliva than in blood. However, according to the ADA, technological advances “have significantly improved the ability to monitor and identify candidate biomarkers at the molecular level.”

Sarah Knox
Sarah Knox

“Efforts are underway to develop miniaturized lab-on-a-chip technology, where diagnostic tests and tools are made to be rapid, automated, and portable,” according to the National Institutes of Health. “Combined with saliva sample collection or cell collection (by gentle brushing of the skin surface), this technology could eliminate the need for blood sampling or mouth tissue biopsy, in many cases.”

The December symposium, which is hosted by the School of Dentistry and Oasis Diagnostics Corp., will feature three keynote speakers:

  • David T.W. Wong, associate dean of research and director of the UCLA Center for Oral/Head and Neck Oncology Research, who will speak on salivary diagnostics and oncology.
  • Sarah Knox, PhD, assistant professor in the Department of Cell & Tissue Biology at the University of California, San Francisco, who will speak on salivary gland organogenesis and regeneration.
  • John McDevitt, PhD, chairperson of biomaterials and biomimetics at New York University and chief scientific officer and founder of SensoDX, LLC, who will speak on salivary diagnostic devices.

The symposium will also include shorter presentations from other speakers, plus poster presentations, and will take place in Hogness Auditorium at the UW’s Magnuson Health Sciences Center. Online registration is being handled by the School of Dentistry.

Dentistry researcher, partners win support for lifesaving infant cup

A global infant-health initiative led by School of Dentistry researcher Dr. Christy McKinney has been nominated for a $250,000 award from a consortium that includes the U.S. Agency for International Development (USAID) and the Bill & Melinda Gates Foundation.

NIFTY Cup
The NIFTY™ cup could benefit millions of infants in the developing world who cannot breastfeed.

Saving Lives at Birth: A Grand Challenge for Development nominated Dr. McKinney and her collaborators for the award to fund research and development of the Neonatal Intuitive Feeding Technology (NIFTY™) cup. The cup makes it easier to feed and prevent starvation among millions of infants in developing countries who cannot breastfeed. Some have physical anomalies such as cleft lip and palate, while others face a higher risk of starvation after being born to mothers who die of childbirth-related causes.

“It’s incredibly gratifying to be nominated for this award that will help fund the crucial next step in our five-year journey to bring this lifesaving tool to the infants who need it,” said Dr. McKinney, a clinical assistant professor at the School of Dentistry who was instrumental in designing the NIFTY™ cup. “It’s astounding that this simple feeding tool has the potential to have such a profound global impact.”

The low-cost, 60-ml cup has several distinct advantages:

  • An extended reservoir off its lip that holds a small bowl of milk, letting the infant pace its own feeding.
  • Mothers can directly express their breastmilk into the cup, reducing possible cross-contamination from other containers.
  • The ergonomically designed cup is made of a durable, soft silicone material that protects the infant’s mouth from injury and can be boiled for sterilization. It dries quickly and is UV-resistant as well.
  • Embossed measurements help track volume and intake of milk.
Dr. Christy McKinney
Dr. Christy McKinney

Dr. McKinney’s collaborators included Dr. Michael Cunningham, medical director of Seattle Children’s hospital Craniofacial Center and an investigator with Seattle Children’s Research Institute’s Center for Developmental and Regenerative Medicine, as well as PATH, a Seattle-based international non-profit organization that forges partnerships to improve global health, especially among women and children.

After Dr. McKinney, Dr. Cunningham and PATH developed a NIFTY™ cup prototype, Dr. McKinney tested it in South India. The team is now using the feedback to refine the cup’s design at the PATH product development shop.

They plan to use the Saving Lives at Birth funding to conduct further studies in Ethiopia and then secure a commercial partner and develop a market strategy and global advocacy plan.

Along with USAID and the Gates Foundation, other members of the Saving Lives at Birth partnership include the Norwegian government, Grand Challenges Canada, the United Kingdom’s Department for International Development, and the Korea International Cooperation Agency.

Student Alexander Stanton receives national research award

Second-year dental student Alexander Stanton has received the American Association of Oral and Maxillofacial Radiology (AAOMR) 2015 Charles R. Morris Student Research Award, the AAOMR has announced.

Alexander Stanton discusses his research during poster presentations at the School of Dentistry’s Research Day in 2014.
Alexander Stanton discusses his research during poster presentations at the School of Dentistry’s Research Day in 2014.

Stanton received the national award for his investigation of the relationship between the angle of the mandibular condyle (a knob on the jaw at the joint) and osteoarthritis-induced degenerative changes. Such changes in the jaw are thought to be linked to temporomandibular disorders including disc displacement and degenerative disease.

He found a link between moderate to severe degenerative changes of condyles and increased condyle  angles, and concluded that assessing the condyle angle could help in diagnosing mandibular degenerative disease and tracking its progression.

Stanton originally performed his study, based on cone beam computed tomography images and reports, for the School of Dentistry’s Summer Research Fellowship (SURF) program in the summer of 2014. His faculty advisers were Dr. Lars Hollender and Dr. Peggy Lee, both of the Department of Oral Medicine.

According to the AAOMR, the Charles R. Morris Student Research Award is designed to encourage new investigators, not yet professionally established, to participate in research to further knowledge in oral and maxillofacial radiology, to develop competency in research and to gain insight into scientific investigation.  The objective is to stimulate the scientific development of promising students and to encourage them to embark on a career in academic oral and maxillofacial radiology.

Along with a $1,000 award, recipients receive an invitation to present their research at the organization’s annual session, plus free AAOMR student membership. Award submissions are based on these criteria:

  • Clarity of conceptual definition
  • Adequacy of literature review
  • Originality
  • Soundness of methodology
  • Significance of contribution to the science of oral and maxillofacial radiology
  • Manuscript format and style

Dr. Salamati receives Sunstar Americas, Inc. Research Award

Dr. Atriya Salamati, a PhD candidate in oral biology at the School of Dentistry, has received the $25,000 Sunstar Americas, Inc. Research Prevention in Oral Health Award, the school has announced.

Award recipient Dr. Atriya Salamati is joined by Dean Joel Berg (left) and Aaron Pfarrer of Sunstar Americas, Inc.
Award recipient Dr. Atriya Salamati is joined by Dean Joel Berg (left) and Aaron Pfarrer of Sunstar Americas, Inc.

Dr. Salamati, who received her DDS degree at the University of Washington in 2013, is pursuing a doctorate in oral biology in the School of Dentistry’s DDS/PhD program. She is studying tooth mobility in both healthy subjects and those with periodontal disease. Her work could eventually help develop better clinical treatment plans for children and adults who are prone to diabetes, periodontal disease, and other conditions leading to loosened teeth.

“I’m beyond thrilled to have received the Sunstar award,” Dr. Salamati said. “This award has helped fund my PhD research project and allowed me to carry out my studies on developing periodontal disease in an animal model and measuring the effect of periodontal disease on the magnitude and direction of tooth displacement.”

This is the second Sunstar Americas, Inc. award presented to a School of Dentistry recipient.  In 2013, Dr. Donald Chi of the Department of Oral Health Sciences faculty received the Sunstar Americas, Inc. Pediatric Prevention Award.

The Sunstar Americas, Inc. Research Prevention in Oral Health Award was created to help identify and support novel approaches to both the diagnosis and prevention of oral diseases, said Aaron Pfarrer, Sunstar’s Senior Director of Professional Relations.

“Sunstar is excited to work with Dean Joel Berg of the School of Dentistry and the University of Washington, both known for significant contributions on these very topics,” he said.

“Sunstar aims to provide funding that not only helps bring new learning to light but also helps spark the interest of others, resulting in a cascade of learning that truly engages others.  Dr. Chi’s and Dr. Salamati’s research exemplifies this approach, expanding and engaging others as their research proceeds,” Pfarrer said.

The School of Dentistry’s Research Advisory Committee chose Dr. Salamati for the award after reviewing research proposals submitted by junior faculty and graduate students. In April, Dr. Salamati was also named a 2015-16 University of Washington Magnuson Scholar, one of the university’s highest academic awards.

“We are exceptionally proud of Atriya and all of her accomplishments,” Dean Berg said. “Her passion for combining her interests in biological science with clinical practice is exemplary. I could not be more pleased with her selection.”

Dr. Salamati said she hopes to begin a residency in pediatric dentistry after completing her PhD. After that, she envisions a career in academic dentistry while also providing patient care and continuing to perform research.

Sunstar, which was founded in Japan in 1932, is a global organization that serves oral health care professionals and consumers in 90 countries. It works directly with researchers and faculty members at dental schools and dental hygiene schools around the world. Sunstar also works closely with dental professional associations and dental student associations to identify and support advances in research and education as well as practical approaches that improve health and enhance quality of life, Pfarrer said.

Targeted bacteria-killer offers promise in fighting tooth decay, other diseases

A new treatment that can kill the bacteria responsible for tooth decay without harming the mouth’s beneficial bacteria has moved one step closer to reality with a study by researchers at the University of Washington and UCLA.

The study, published in the June issue of the Proceedings of the National Academy of Sciences, shows how a specifically targeted antimicrobial peptide, or STAMP, known as C16G2 eradicates harmful acid-producing Streptococcus mutans bacteria without killing benign bacteria.

A Streptococcus mutans bacterium is shown before (left) and after treatment with the C16G2 specifically targeted antimicrobial peptide.
A Streptococcus mutans bacterium is shown before (left) and after treatment with the C16G2 specifically targeted antimicrobial peptide. Dr. Wenyuan Shi/UCLA School of Dentistry

 

The finding is a critical advance because, as scientists have understood for about two decades, the vast majority of bacterial cells in the human mouth are not harmful. However, most common broad-spectrum antibiotics and conventional mouthwashes indiscriminately kill both beneficial and harmful bacteria, and their effects last for only about 12 hours.

In addition, overusing broad-spectrum antibiotics can not only increase bacterial resistance, but also seriously disrupt the body’s ecological balance, which can make people more susceptible to microbial infections. As a result, there is no effective treatment for bacteria-induced tooth decay. While fluoride has been an effective weapon against tooth decay, it works by strengthening tooth enamel rather than attacking the Streptococcus mutans bacteria, which convert sucrose to lactic acid that attacks the teeth.

The STAMP approach, on the other hand, restructures the mouth’s microbiome, or microorganism population, to produce an environment that supports better oral health. Moreover, the STAMP approach could possibly be used against other microbiome-related diseases, meaning it could have an impact far beyond dentistry, said Dr. Dr. Wenyuan Shi, the study’s lead author and chair of the section of oral biology at the UCLA School of Dentistry.

Dr. Jeffrey McLean
Dr. Jeffrey McLean

A growing number of studies have linked  changes in the composition of the human microbiome to numerous disease states. When bacteria cause diseases, it is typically because they grow beyond their normal population size or niche (which can occur when the body’s immune system is compromised), or because microbes enter parts of the body that are normally sterile, such as the blood, lower respiratory tract or abdominal cavity.

“This is a truly momentous discovery that provides proof-of-concept on re-engineering human microbiome for treatment and prevention of diseases,” Dr. Shi said. “It demonstrates that this targeted approach actually works and that it is an incredibly powerful tool that can be used to manipulate our microbiomes.”

The researchers’ latest work builds on earlier studies that led Dr. Shi to develop an experimental STAMP mouthwash in 2011. The new study shows that the STAMP, in addition to eradicating  Streptococcus mutans, also increased the abundance of  other Streptococcus species that are highly prevalent in healthy oral cavities, including one that is strongly linked with healthy dental plaque.

Study co-author Dr. Jeffrey McLean of the University of Washington School of Dentistry said, “Targeted killing of individual species that can trigger or significantly advance disease within our delicately poised microbiome is crucial to keep the entire system in balance. Importantly, this study also represents a major step towards understanding how that balance may be shifted towards a healthy state after removing a single disruptive member of the human microbiome community.”

The C16G2 STAMP is now delivered via a gel tray, which the researchers have chosen as a more promising vehicle than the mouthwash. It is being developed for use in preventing tooth decay and cavities under an investigational new drug application with the U.S. Food and Drug Administration by Los Angeles-based C3 Jian, a company Dr. Shi founded around patent rights he developed at UCLA. It is currently in Phase 2 clinical trials.

Dr. John Mekalanos, chair of microbiology and molecular genetics at Harvard Medical School, and the article’s editor, said, “The challenge of trying to modulate the abundance of a single member of our complex microbiota is enormous. Dr. Shi and his colleagues have provided an exciting new way to do just that.”

The study’s other main authors include Dr. Xuesong He of UCLA Dentistry and Brian Varnum of C3 Jian. The study was supported by the National Institutes of Health and by C3 Jian.

Dentistry faculty helps lead Latin American research workshop

School of Dentistry faculty members helped lead the second Latin American Workshop on Clinical Research Methods in Oral Health, held Feb. 22-27 at Cayetano Heredia University in Lima, Peru.

Latin American Workshop
University of Washington faculty presenters at the second Latin American Workshop on Clinical Research Methods in Oral Health in Lima, Peru included (all in front row) Dr. Timothy DeRouen (fourth from left), Dr. Susan Coldwell (third from right), Dr. Charles Spiekerman (second from right) and Dr. Ana Lucia Seminario (far right). Workshop faculty also included Dr. Lilliam Pinzon (third from left) of the University of California at San Francisco and Dr. Jorge Luis Castillo (second from left), who received his orthodontics specialty training at the UW and is now chair of pediatric dentistry at Caetano Heredia University.

The conference, whose theme was “An Update on HIV,” was conducted jointly with the University of Washington School of Public Health. Dr. Joseph Zunt, Professor of Neurology and Professor of Global Health in that school, was principal investigator on a Fogarty International Center training grant that funded the conference.

Thirty-two people attended this year’s conference, drawn from a pool of about 70 applicants made up mostly of junior faculty from Latin American universities.

Dentistry faculty presenters included:

  • Susan Coldwell, Associate Dean (behavioral sciences)
  • Timothy DeRouen, Director of the Center for Global Oral Health (randomized clinical trials)
  • Ana Lucia Seminario, Pediatric Dentistry (epidemiology)
  • Charles Spiekerman (biostatistics)

Dentistry alumnus Dr. Jorge Luis Castillo (Orthodontics Class of 2000), chair of pediatric dentistry at Caetano Heredia University, was a conference faculty member, as he was last year. The faculty also included Dr. Lilliam Pinzon of the University of California at San Francisco.

Last year’s workshop, which was also held at Cayetano Heredia University, marked the School of Dentistry’s first clinical training research foray into the Southern Hemisphere. The workshop is a shorter version of the school’s annual six-week Summer Institute in Clinical Dental Research Methods, which has helped hone the skills of researchers from around the world for more than 20 years.

Dr. Seminario, who also helped organize the 2014 workshop, said last year that it underscored the value of a face-to-face presentation.

“Culturally, it has a lot of impact when someone from a developed country goes to a developing country,” she said. “It also shows us the need for more training, and our goal is to encourage more evidence-based research.”

David Shin, Dr. Emily Chu win Research Day honors

Second-year student David Shin and oral biology graduate student Dr. Emily Chu won top honors in poster competitions during the School of Dentistry’s annual Research Day on Sept. 19 at the UW Health Sciences Center.

Research Day pre-doctoral poster competition finalists were (from left) Alex Stanton, Isabella Weng, David Ludwig, Moniqu Luu, David Shin and Adam Szajman.
Research Day pre-doctoral poster competition finalists were (from left) Alex Stanton, Isabella Weng, David Ludwig, Moniqu Luu, David Shin and Adam Szajman.

Shin won the pre-doctoral student competition and was named to receive the 2014 American Dental Association (ADA) Student Clinician Award. David Ludwig, president of the Class of 2015, earned second place in the pre-doctoral competition, while first-year student Alex Stanton won third place.

Shin’s project, “Condylar Bone Loss After Repeated Botox Injections in Rabbit Masseter,” was co-authored by Dr. Kathy Rafferty, and he was mentored by Dr. Sue Herring of the Departments of Orthodontics and Oral Health Sciences. He will represent School of Dentistry at the National Student Research Competition at the November 2015 ADA meetings in Washington, D.C. Shin also received a $200 prize from the UW chapter of the Omicron Kappa Upsilon dental honorary society, which co-sponsored the competitions along with the Seattle Section of the American Association for Dental Research (AADR).

Dr. Chu
Dr. Emily Chu discusses her work during the Research Day poster presentation.

Dr. Chu, of the Department of Oral Health Sciences, won the first-ever graduate student/trainee research competition, which was organized by AADR’s Seattle Section. Her project, “Investigating Contributions of the CLP Protein, IRF6, in Orofacial Ectodermal Polarity Using a Tooth Model,” was co-authored by M.R. LaCourse and B.L. Foster, and she was mentored by Dr. Martha Somerman of the National Institute for Dental and Craniofacial Research and Dr. Timothy Cox of the UW Department of Pediatrics. Dr. Chu, who received her DDS from the UW in 2012, won a $100 prize from the AADR Seattle Section.

Dr. Gregory Wilson, Associate Professor of Biology at the UW, presented the day’s keynote speech, “An Odontologist’s Delight: A View of Mammalian Evolution.” School of Dentistry faculty also gave oral presentations:

  • Dr. Daniel Chan, Professor of Restorative Dentistry and Associate Dean for Clinical Services, discussed his research on dental hard tissue.
  • Dr. Avina Paranjpe, Assistant Professor of Endodontics, discussed research on dental pulp.
  • Dr. Tracy Popowics, Associate Professor of Oral Health Sciences, discussed research on periodontal ligament fibroblasts.

Dr. Darveau, colleagues shed new light on link between gum disease, vascular inflammation

A new journal publication co-authored by Dr. Richard Darveau, Chair of the Department of Periodontics, has shed further light on how the bacterium that causes periodontal disease can evade the body’s immune response and trigger inflammation in blood vessels outside the oral cavity.

Dr. DarveauThe study by Dr. Darveau and several co-authors was published in the current issue of PLOS Pathogens.

“We had published earlier that this mechanism could be used by P. gingivalis to evade host detection, and this paper is the first to demonstrate it in an animal model of disease,” Dr. Darveau said.

The findings by Dr. Darveau, Dr. Caroline Attardo Genco of the Boston University School of Medicine and their colleagues hold broader implications in light of a growing body of evidence that ties chronic inflammation to an elevated risk of serious illnesses such as heart disease, cancer and diabetes.

The PLOS Pathogens paper focuses on Porphyromonas gingivalis, a pathogen that causes periodontal or gum disease, and its link to atherosclerosis. According to a PLOS summary of the paper, P. gingivalis and other gram-negative bacteria have an outer layer comprising sugars and lipids. The immune system recognizes parts of this coating and swings into action. In turn, P. gingivalis modifies its outer coat to avoid the immune system’s counterattack.

The researchers focused on a specific lipid on the outer surface of P. gingivalis, called lipid A, which is known to interact with a key regulator of the host’s immune system called TLR4. P. gingivalis can produce different versions of lipid A, and the researchers sought to explain how these alter the immune response and allow the pathogen to survive and cause inflammation.

They concluded: “P. gingivalis modifies its lipid A structure in order to evade host defenses and establish chronic infection leading to persistent systemic low-grade inflammation.” They also found an attribute unique to P. gingivalis among gram-negative pathogens: “P. gingivalis evasion of TLR4-mediated host immunity results in progression of inflammation at a site that is distant from local infection by gaining access to the vasculature.”

Earlier this year, Dr. Darveau was elected a Fellow of the American Academy of Microbiology. He also  received the American Association for Dental Research/International Association for Dental Research William J. Gies Award in the Biological Research category.

UW leads oral health research workshop in Peru

In May, the School of Dentistry led a weeklong workshop in Peru that expanded its clinical research training activity into the Southern Hemisphere for the first time.

The First Latin American Workshop on Clinical Research Methods in Oral Health, held May 12-16 at  Cayetano Heredia University in Lima, marked an extension of similar training the UW has offered for more than two decades in Seattle and in Asia.

UW SOD in latin America
UW faculty members leading the First Latin American Workshop on Clinical Research Methods in Lima, Peru included (front row) Dr. Joanna Scott (far left), Dr. Lisa Heaton (second from left), Dr. Tim DeRouen (third from right) and Dr. Ana Lucia Seminario (far right). Another key participant was Dr. Jorge Luis Castillo (front row center), who received his orthodontics specialty training at the UW and is now chair of pediatric dentistry at Caetano Heredia University and president of the International Association of Pediatric Dentistry.

The 35 participants, culled from 60 applicants, represented mostly junior faculty from Latin American colleges and universities who had a strong interest in oral health research, according to Dr. Ana Lucia Seminario, one of the workshop organizers along with Dr. Tim DeRouen, director of the Center for Global Oral Health at the UW. Since 1992, he has directed the Summer Institute in Clinical Dental Research Methods, and for the last several years has led clinical research training sessions at several universities in Thailand under a grant from the Fogarty International Center of the National Institutes of Health. He is also the president of the American Association for Dental Research for 2014-15.

The Peru Workshop, also supported by a $25,000 Fogarty grant, was led by School of Dentistry faculty including Dr. DeRouen and Dr. Seminario, as well as Dr. Joanna Scott and Dr. Lisa Heaton. The workshop faculty also included the UW’s Deborah Dickstein, from the Division of Human Subjects, and Dr. Jorge Luis Castillo, chair of pediatric dentistry at Caetano Heredia University and president of the International Association of Pediatric Dentistry. Dr. Castillo also completed orthodontics residency training at the UW in 2000.

The workshop covered subjects including:

Introduction to epidemiologic research methods

  • Behavioral research in dentistry
  • Randomized Clinical Trials
  • Ethical issues
  • Biostatistics
  • Study design

Dr. Seminario said the workshop underscored the value of a face-to-face presentation.

“Culturally, it has a lot of impact when someone from a developed country goes to a developing country,” she said. “It also shows us the need for more training, and our goal is to encourage more evidence-based research.”

School researchers patent new antibacterial agent

Four School of Dentistry faculty members have received a patent for a new way of using titanium-based materials to fight oral bacteria.

The patent culminates several years of work in which the group studied a novel class of substances called titanates and peroxotitanates, which can inhibit bacterial growth when bound to metal ions. These titanates could be incorporated into a gel or a solution that would be applied by a dentist after a procedure such as a root canal or a filling, reducing the chances of infection or tooth decay at that site.

Titanates could also be used in bandages, skin gels, mouthwashes and toothpaste to limit bacterial growth, said Dr. Whasun Oh Chung, one of the four researchers. The others are Dr. Daniel Chan, Dr. Bruce Rutherford and Dr. John Wataha.

The group’s work grew out of nearly a decade of research performed by Dr. Wataha and Dr. David Hobbs of South Carolina’s Savannah River National Laboratory, who is also listed on the patent as an inventor.  Their studies formed the basis for a four-year, $1.5 million federal grant by the National Institute of Dental and Craniofacial Research to the School to evaluate titanates’ antibacterial properties.

Dr. Chan, the School of Dentistry’s associate dean for clinical services, was co-principal investigator on the grant with Dr. James Bryers of the UW Department of Bioengineering.  Dr. Chung and another School of Dentistry faculty member, Dr. Albert K.H. Chung, were co-investigators.  Dr. Charles Spiekerman of the School of Dentistry’s Department of Oral Health Sciences is the group’s biostatistician, while Dr. Wataha, a member of the school’s Department of Restorative Dentistry, is  a consultant. Dr. Hobbs also was involved in securing the grant.

Metals have long been known to have antibacterial properties, said Dr. Whasun Oh Chung, but when used in concentrations high enough to be effective, they also carry a risk of toxic side effects. What makes the work with titanates promising, she said, is that the therapeutic benefits are achieved with less risk of toxicity.

“It is very new and novel,” said Dr. Chung. “Nothing has delivered materials at such a non-toxic level. We’re working with something we know is effective. Metals have been around a long time, and the bacteria haven’t become resistant to them.”

That is also an important consideration at a time when growing bacterial resistance to antibiotics places greater urgency on the need to find antimicrobial alternatives, she noted.

“The use of metal ions to control bacterial infections remains of interest as drug-resistant bacteria are becoming increasingly common and dangerous to human health,” Dr. Chung said.

Aside from their uses in the mouth or other topical applications, titanates could even be used in narrowly targeted treatments for internal organs, she said.

Titanates could also be used in dental or medical materials and devices, she said, including suture material, catheters, shunts, and dental fillings. They could even show up in toothpastes and mouthwashes some day, she said.

“[Titanate-metal complexes have] proven to be effective against endodontic, cariogenic  and periodontic bacteria,” Dr. Chung said. “The idea is to make it easy for people to use every day.” At the same time, Dr. Wataha cautioned that the practical or clinical benefits have yet to be conclusively demonstrated for the new patent-related application.

The researchers are now conducting human trials and expect to finish this spring, Dr. Chung said. However, she declined to predict when titanates might be approved for general use.

 

Sunstar Americas boosts UW pediatric oral health research

Dr. Donald Chi of the UW Department of Oral Health Sciences faculty has been named the recipient of the initial Sunstar Americas Pediatric Prevention Award.

Dr. ChiDr. Chi received the new $25,000 unrestricted award to conduct research on pediatric oral health. He plans to study the risk of caries in children and adolescents with cystic fibrosis (CF).

“I’m delighted that Sunstar’s support will help this outstanding young teacher and researcher make an important contribution to our understanding of this element of oral health,” said Dean Joel Berg. The award from Sunstar, a leading maker of oral care and other health care products, is intended to support the study of prevention in pediatric dentistry.

Dr. Chi’s research will examine why children with CF appear to lose their protection against caries as they age into adolescence. One possible explanation, according to Dr. Chi’s research abstract, may lie in the fact that children with CF are typically prescribed varieties of penicillin that kill the Gram-positive oral bacteria that cause decay. Adolescents with CF, however, generally receive a different form of inhaled antibiotic that is not effective against Gram-positive bacteria.

Dr. Chi’s main collaborators are Dr. Sun Oh Chung of Oral Health Sciences, who was also his mentor for the award, and Drs. Margaret Rosenfeld and Ronald Gibson of Seattle Children’s hospital. Their work will also be aided by an additional $80,000 from the Cystic Fibrosis Research Developmental Program, an initiative funded by the CF Foundation.

Dr. Chi said he was extremely gratified to receive the Sunstar award, and added: “These funds will support the largest U.S.-based clinical oral health study of children and adolescents with CF since 1980. Our team is honored and thrilled for the opportunity to conduct important translational research that will advance our understanding of oral diseases in patients with CF.  We will work hard to generate knowledge that we hope will ultimately optimize the dental care we provide to patients with CF.”

Along with his position as assistant professor of Oral Health Sciences, Dr. Chi is also an  investigator at the UW’s Northwest Center to Reduce Oral Health Disparities. He holds board certifications in pediatric dentistry and dental public health.

He has recorded 45 contributions to peer-reviewed journals, along with 36 published research abstracts and three book chapters. Among his numerous recognitions are two awarded this year:  the Bengt Magnusson Memorial Prize in Child Dental Health and a five-year appointment as  a William T. Grant Foundation Scholar.

Dr. Larry Kessler to present keynote talk at Research Day

Dr. Larry Kessler, Chair of the UW Department of Health Services, will discuss “Regulatory and Scientific Challenges in Advancing Dental Technology” in the keynote address at the School of Dentistry’s annual Research Day on Friday, Sept. 20.

Dr. Larry KesslerDr. Kessler, who is also Adjunct Professor of Pharmacy at the UW, served as Director of the Food and Drug Administration’s Office of Surveillance and Biometrics, Center for Devices and Radiological Health until 2008. From 1984 to 1995, he headed and developed the Applied Research Branch at the National Cancer Institute. In 2001, he spent a year as a visiting scientist at the Fred Hutchinson Cancer Research Center and served on the faculty of the Department of Health Services.

His research focuses on the cost-effectiveness and diagnostic value of medical technology in screening for cancer and other diseases.

Dr. Kessler’s talk will be followed by presentations from School of Dentistry faculty:

  • Dr. Johan Aps, Clinical Associate Professor of Pediatric Dentistry, will discuss his research on new imaging modalities in the diagnosis of dental and craniofacial diseases.
  • Dr. Richard Presland, Associate Professor and Graduate Program Director, will discuss his research on salivary diagnostics in graft-versus-host disease.
  • Dr. Mark Drangsholt, Chair of the Department of Oral Medicine and Professor of Oral Medicine and Oral Health Sciences, will discuss his research on quantitative sensory testing in the diagnosis of orofacial pain.

Research Day lectures will be held in Room T-625 of the UW Health Sciences Center from 8:15 to 10:50 a.m., followed by student poster presentations in the Health Sciences Center lobby  from 11:00 a.m. to 12:30 p.m.

Grad Pros resident earns top research honor

Dr. Marta Revilla, a third-year UW Graduate Prosthodontics resident, was awarded first place in the 2013 Pacific Coast Society of Prosthodontics Graduate Student Research Competition at this year’s annual session in Anchorage, Alaska.  Dr. Revilla’s research was titled “Influence of Fluorescence on the Color Perception of Lithium Disilicate Glass Ceramic with Different Ceramic Thicknesses and Glaze Pastes.”

Marta RevillaDr. Revilla  and four other residents from Pacific Coast universities, including Dr. Tijana Stijacic and Dr. Blake Barney from the UW, presented their research on the opening day with the headline speakers. Dr. Revilla received a $1,500 cash award for first place.

Dr. John Sorensen of the Department of Restorative Dentistry, her mentor on the research project, said, “It is extremely satisfying to see such a strong UW presence in the Prosthodontic Graduate student research competition with three of our residents being selected to compete and present their research and then have Dr. Revilla win first place.”

The annual session took place June 27-29, with Dean Joel Berg among those attending from the UW. Dr. Sorensen was also a program co-chair and speaker at the session.