GOAL ONE: Bring the best science to bear on problems in oral, dental and craniofacial health.
Science is advancing rapidly, and the next generation of technological innovation may greatly accelerate the next breakthroughs in oral, dental and craniofacial research. Researchers have already created prototypes for "labs-on-a-chip," bioengineered tissue replacements, and developed powerful molecular imaging tools that provide a new window into complex biological systems about which we continue to learn. This emerging wave of knowledge and tools will accelerate the development of molecular-based oral health care, and thus it is vital that the NIDCR support a diverse portfolio of research to achieve that end.
Objective I-1: Integrate molecular, clinical, and population health approaches to improve diagnostics and optimize outcomes.
Most oral diseases and disorders arise from the interplay of complex biological, behavioral, environmental and genetic factors. Scientists now have the tools to understand health and disease from a powerful systems perspective. Such deep insights will enhance our ability to predict and more effectively manage many oral, dental diseases and craniofacial abnormalities such as orofacial clefting and ectodermal dysplasias. However, understanding and addressing complex oral diseases will take more than figuring out the molecular pieces of the puzzle. It will require melding these advances with state-of-the-science clinical, epidemiological and bioinformatics approaches to more precisely identify diseases at their earliest inception, direct individualized therapies, and predict disease outcomes.
The NIDCR will support a variety of efforts to integrate the basic, clinical, and population sciences to help clinicians devise prevention strategies, early detection and diagnostic tools and personalized therapies. Oral health research stands to benefit greatly from this complementary and integrated approach.
Scientists now have the tools to understand health and disease from a powerful systems perspective.
One area that offers considerable opportunity is oral and pharyngeal cancer, which kills about 7,600 Americans each year. These deaths are particularly tragic because, in most cases, detection and treatment of early stage oral cancer results in much higher survival rates than if the disease is diagnosed and treated at late stages. Despite annual U.S. spending of approximately $3.2 billion1 on head and neck cancer treatment, relative survival rates have not improved during the past 16 years and remain among the lowest of all major cancers. Oral cancer survival among African American men has actually decreased2. The NIDCR will support development of a multifaceted program that integrates several new technologies and methods into a clinical protocol aimed to improve oral cancer detection and survival. Approaches under development include devices to aid in earlier detection: rapid gene-expression measurement tools that assess suspicious lesions removed for biopsy, and integration of screening, diagnosis and treatment. For example, toward achieving this goal, NIDCR-supported researchers recently devised a customized optical device3 that allows clinicians to visualize in a completely new way areas in the oral cavity that may be developing oral cancer. An Institute priority is to conjoin these efforts with the results of research to reduce oral cancer in high-risk groups. Approaches include genetic association studies and research on improving community outreach, education and behavioral modification.
Dental caries, or tooth decay, offers another prime example where an integrative approach could offer new therapeutic insights. Over the last several decades, dental researchers have made tremendous progress in defining events in the decay process and learning how to reverse them. However, more precise identification of the genes and pathways that characterize decay will allow scientists to more clearly define how bacteria thrive and communicate within a biofilm. The Institute also will support research to further develop and refine sensitive imaging tools that will enable detection of the earliest signs of enamel demineralization. Approaches to halt and remineralize these early lesions would save the tooth from further decay and avert the need for invasive restorations. Recognizing the role of oral health behavior in tooth decay—and especially the role of families in the development of childhood caries—the Institute seeks to recruit the interest of behavioral science experts to investigate the role of behavioral change in oral health improvement.
The integration of existing knowledge with the results of genetic, behavioral, epidemiological and clinical studies will identify practical solutions to confront stubbornly evasive conditions such as HIV/AIDS-associated oral diseases, temporomandibular muscle and joint disorders, and a host of other conditions affecting the craniofacial complex.
Objective I-2: Increase the Institute's commitment to basic and applied research in the behavioral and social sciences.
Community characteristics and the organization of health care systems are key aspects of the social context that contribute to oral health. Many of the opportunities for improving oral health lie in achieving behavioral, lifestyle and social changes—objectives that are shared with many other scientific areas.
Drawing from the expertise of diverse fields within the social and behavioral sciences presents an important opportunity to develop models and approaches that will produce meaningful improvements in oral health. This approach dovetails with the view of oral health as an essential component of general health as cited in the Surgeon General's report on oral health in America (2000)4.
The NIDCR will seek to engage researchers in child development, family theories, social systems, geriatrics, and treatment adherence to broaden the understanding of oral health and frame new approaches to improve it. Other vital areas for NIDCR investment include behavioral interventions in non-dental settings, interventions for reducing risk behaviors and the integration of evidence-based health recommendations into communities. Recognition of multiple principal investigators on NIH research applications5 should smooth the way for such collaborations across and within disciplines.
Objective I-3: Embrace and support research discovery through genetic, genomic and proteomic approaches to understanding oral, dental and craniofacial disease.
The NIDCR will prioritize research that exploits advances in the genetics, genomics and proteomics of dental, oral and craniofacial diseases. The development of quantitative approaches to better understand the developmental and physiological circuitry underlying craniofacial structures in both health and disease will play an increasingly important role. Bioinformatics and computational approaches are necessary to integrate, analyze and model the large data sets generated by these modern research tools. The Institute also will encourage efforts to share bioinformatics platforms between intramural and extramural projects.
The emerging science of genome-wide association studies, or GWAS, and other rapidly evolving genome-wide technologies is producing exciting findings in oral, dental and craniofacial health, including those from an ongoing NIDCR-funded GWAS of oral clefts and dental caries. A recent family-based genome-wide linkage study indicated possible developmental links between cleft lip and/or palate, caries and a range of dental malformations8 and identified several candidate genes for caries risk, pointing unexpectedly to genetic loci for salivary flow and diet preference9. The NIDCR's continued support of genomic approaches may yield important new insights into the causes and progression of other complex conditions such as temporomandibular muscle and joint disorders associated with chronic orofacial pain, oral cancer, periodontal diseases and Sjögren's syndrome. Research to elucidate the fundamental biological mechanisms and pathways of oral diseases will be required to translate the findings from genome-wide association studies into clinical applications.
In addition to funding innovative, investigator-initiated genomics and proteomics projects, the NIDCR supports the recently launched FaceBase Consortium10. This project will establish a publicly available database to serve as a resource that will promote enhanced understanding of the genetic and environmental influences that drive craniofacial development. These efforts will likely yield new opportunities for preventing and treating craniofacial defects. The FaceBase Consortium will provide researchers a portal and a platform to provide access to large data sets. This will facilitate the analysis, integration and dissemination of research results, fostering interactions and collaborations with the Consortium and with the broader scientific community. The Consortium will also house projects for the development of novel methods and technologies that could be applied to probe molecular, cellular and physiological processes during craniofacial development.
Objective I-4: Promote the oral cavity as a model for understanding other organ systems and diagnosing a range of health conditions.
NIDCR-supported research using the oral cavity as a research tool and delivery platform will pave the way to a future of targeted therapies for a range of conditions. Therapeutic manipulation of immune and/or humoral responses through gene delivery approaches such as RNA interference via the oral cavity may lead to better control of autoimmune diseases such as Sjögren's syndrome, which destroys salivary function and the production and secretion of tears. Another expected benefit of immune modulation via the mouth is the potential for novel ways to halt the chronic inflammation that contributes to periodontal disease, a condition that affects an estimated 80 percent of U.S. adults and has a well-documented link with diabetes11, 12.
The ease of access of the oral cavity makes it an ideal model for research on multiple questions including oral HIV transmission, dissemination and pathogenesis; oral manifestations initiated by multiple oral infectious pathogens; AIDS-related oral malignancies; and mechanisms of immunosuppression.
Saliva-based diagnostic tests offer significant potential for improving both oral and general health. Thus further development and validation of these approaches will enable improved preemptive care by detecting molecular markers predictive of disease before symptoms arise, or by providing diagnosis of the earliest signs of disease. Recently, a consortium of NIDCR-supported research groups compiled the first comprehensive list of proteins secreted by the major salivary glands13, leading to a compendium of salivary proteins that will form the basis for future efforts in salivary diagnostics and therapeutics.
The NIDCR participates in the trans-NIH Human Microbiome Project14, which will lay a foundation for efforts to explore how complex communities of microbes interact with the human body to influence health and disease. This project supports the development of innovative technologies and computational tools; coordination of data analysis; and an examination of ethical, legal and social implications of human microbiome research. The choice of five sampling sites—the skin, vagina, gastrointestinal tract, nose and oral cavity—will enable a broad-based discovery approach that will have important implications for systemic health in addition to oral, dental and craniofacial health.
Objective I-5: Facilitate reconstruction and regeneration of diseased or damaged oral and craniofacial tissues and organs through biological, bioengineering and biomaterials research approaches.
Creating fully functional craniofacial bone, salivary glands, and artificial teeth with performance properties equivalent to natural tissues or organs is also an Institute priority...
The NIDCR has a longstanding interest in oral, dental and craniofacial tissue and organ reconstruction and regeneration, and was a pioneer in the study of the chemical properties and molecular structure of collagen and other extracellular matrix components—key elements of bones, teeth and the periodontium (the tissues that surround and support teeth). The ultimate goal of tissue engineering and regenerative medicine is to create, rebuild and preserve permanent, functional tissues by applying both biological and engineering principles. Future efforts capturing new knowledge in developmental biology, immunology and computational modeling provides unprecedented opportunity to develop biomimetic and bioengineering tools that coax the body to repair itself. Creating fully functional craniofacial bone, salivary glands, and artificial teeth with performance properties equivalent to natural tissues or organs is also an Institute priority area with potential for significant impact on a range of conditions.
NIDCR-funded research in craniofacial tissue and organ reconstruction will not only inform approaches to correct craniofacial birth defects, but also address the urgent needs of the thousands of Americans who suffer disfiguring wounds and chronic pain from accidents or military conflicts. Through the integration of tissue engineering and regenerative medicine, biomaterials approaches, nanotechnology efforts, and stem cell research, NIDCR-supported scientists will create new options for reconstructing malformed parts of the craniofacial complex or injured tissues of the face and head caused by severe trauma. Cutting-edge techniques, such as stem cell-mediated regeneration, have the potential to supplant the use of artificial materials—metals, plastics, and latex—that are limited in their ability to functionally replace missing structures.
Even today, virtually everyone in the U.S. is at risk for tooth decay, which remains the single most common chronic childhood disease—five times more common than asthma4. Despite steady progress in learning how to better formulate and cure, or harden, dental composites in a damaged tooth, large composites shrink and stress the teeth to which they are bonded. Studies have shown that dental resin composites have an average replacement time of 5.7 years due to secondary decay and fracture of the restoration15. It will thus be important to improve our ability to predict the structural and mechanical properties of dental materials and develop stronger and longer-lasting restorations. The NIDCR will support research that explores whether oral biofilms accelerate the degradation of dental resin composites, leading to secondary decay and restoration failure, as previous studies have suggested. The Institute also will support research toward a new generation of materials, including nanocomposites and smart self-healing materials with enhanced adhesive bonding to a tooth's surface, improved durability, better aesthetics, and maximum biocompatibility.