NIDCR Workshop: Study of Mineralized Tissues as a Paradigm for Integration of Dental, Oral, and Craniofacial Diseases with Other Physiological Systems

September 11-12, 2019
Bethesda, Md.

NIDCR envisions a future where dental, oral, and craniofacial (DOC) health and disease are understood in the context of the whole body. Fully integrating oral health into the study of overall health is one of the five goals of NIDCR 2030, a strategic visioning initiative to guide the next 15 years of DOC research.

In mineralized tissues research, advances in knowledge of rare and understudied disease mechanisms have provided insights into the biological underpinnings of more prevalent diseases within and outside of the DOC complex, including osteoporosis, periodontal disease, and other skeletal inflammatory conditions. Insights gained from studies of DOC diseases can inform understanding of diseases in other organ systems, and vice versa.

To explore ways to enhance this cross-fertilization, NIDCR convened “Study of Mineralized Tissues as a Paradigm for Integration of Dental, Oral, and Craniofacial Diseases with Other Physiological Systems.” The workshop, held in September 2019 in Bethesda, Md., drew experts in genetics, pathology, dentistry, surgery, craniofacial biology, veterinary science, and patient advocacy. Their charge was to identify gaps and opportunities for integrating DOC and non-DOC research and chart strategies and recommendations to guide future integrative research. 

Disease- and organ-specific siloing of biomedical research impedes integrative science, according to workshop participants. One strategy to overcome this barrier is to better leverage community-wide scientific resources. Linking and centralizing existing trans-disciplinary bioinformatics resources (e.g., International Mouse Phenotyping Consortium, Online Mendelian Inheritance in Man, FaceBase, and Genotype Tissue Expression (GTEx)) is one potential solution. Machine learning/artificial intelligence could be used to mine, compile, link, and standardize data from various platforms. Some of the participants cited the potential usefulness of merging research data with patients’ dental and medical records. Another potentially valuable resource is a database designed to link scientists with similar interests from different fields; one existing platform connects investigators interested in the same gene for disease gene discovery. 

Similar trans-disciplinary opportunities exist for collecting data. Workshop participants called for more concerted efforts to include DOC tissues and cells in unbiased platform science, centralized biorepositories, and “whole body” research (e.g., All of Us, tissue chips). These approaches might encourage comparisons of molecular and cellular mechanisms, disease pathogenesis, and treatment responses across different tissue types.

While community-wide scientific resources are potentially powerful tools for integrative science, researchers are often unaware they exist. The workshop participants recommended developing strategies to better inform and update the research community on the full array of available tools.  

Another way to overcome biomedical research siloing is through culture and behavior change. Participants agreed that institutions could do more to foster interactions and collaborations among scientists and clinicians from different disciplines, starting at the training stage. Schools could develop curricula that facilitate interactions among dental, medical, pharmacy, nursing, veterinary, and doctoral students. NIH institutes and centers could build on existing efforts to collaborate on exploratory workshops, research and training grants, and grant review panels specifically geared toward cross-discipline collaboration and integrative science. Participants cited the need for formal training in how to initiate, develop, and maintain successful research collaborations. 

Patient advocacy groups and professional societies are important partners in driving culture change. Workshop participants discussed strategies to increase the inclusion of speakers and sessions from outside fields at professional society conferences. Funding organizations could offer support via travel grants and session sponsorships. Patient advocacy groups can be important champions for inclusion of integrative events at scientific conferences. More broadly, patient advocacy groups can be key players in outreach and engagement of patients, clinicians, dentists, and scientists in integrative research. The workshop participants also suggested cultivating opinion leaders in the DOC field who can raise awareness (such as at non-DOC meetings) and request inclusion of DOC measures in trans-disciplinary research efforts (e.g., Helping End Addiction Longterm (HEAL) and All of Us).

Workshop participants discussed another major hurdle to integrative science: the time and cost required for scientists to gather the pilot data needed to expand their research into a new disease or tissue. Supplemental funding opportunities for exploratory studies could provide researchers with the critical support needed to gather enough data to obtain new grants. Another potential strategy is to generate pilot data using artificial intelligence, machine learning, and mathematical modeling to rapidly predict effects in other systems. With these methods, it’s possible to generate data in a matter of minutes that would otherwise take years to collect manually. NIH intramural scientists looking to explore a new area could join existing clinical protocols as co-investigators before deciding to commit the time and effort required for developing a new protocol.

Next, the workshop participants discussed strategies for expanding DOC tissue knowledge to non-DOC tissues and vice versa. Focusing on understanding common, basic biological processes such as stem cell/developmental biology, microbiology, immunology, and cancer mechanisms can lead to insights about both DOC and non-DOC tissue. Participants called for more robust efforts to convey the utility of DOC-specific animal and human models and the mouth’s accessibility for non-DOC research. 

Participants addressed ways to encourage the DOC research community to adopt tools and methods successfully employed in other fields. Mineralized tissue researchers have been slower to adopt molecular technologies widely used in other fields because of the inherent difficulty in working with the unique molecular features of mineralized tissue. More generally, 3D modeling/printing, biomarker collection, and ‘omics technologies could be more widely applied in DOC tissue research. The holistic approach used in veterinary research to understand biology is informative, and collaborations with veterinarians may be valuable. Veterinarians can lend expertise in identifying useful, naturally occurring animal models with DOC manifestations (e.g., tooth resorption in cats, gingival hyperplasia in dogs).
Finally, participants discussed the possibility of developing an integrative science funding program that compiles many of the resources discussed over the course of the workshop under one large umbrella of support. Such a program might provide features including core support, an inventory of available community resources (bioinformatics, tissue, and computational platforms), supplemental funding for exploratory research, education in effective team science, conference support, and more. 

At the conclusion of the workshop, participants summarized the strategies, suggestions, and recommendations that emerged over the course of the discussions. NIDCR will carefully consider this input to chart directions for future research-related efforts.