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Dental, Oral, and Craniofacial Research: the View from the NIDCR

NIDCR, Building 31, Room 2C39, 31 Center Drive, MSC 2290, Bethesda, MD 20892-2290; Lawrence.Tabak{at}nih.gov

Key Words: NIDCR • research • strategic plan

The man who dreamed up personal computing and laptop computers, Dr. Alan Kay, once said: "The best way to predict the future is to invent it." The dental research community is inventing a future in which all people will enjoy good dental, oral, and craniofacial health. There’s every reason to predict that we will succeed. Consider the rest of Dr. Kay’s statement: "Really smart people with reasonable funding can do just about anything that doesn’t violate too many of Newton’s Laws."

It’s no exaggeration to say that we are standing on the threshold of an unprecedented time in science. Think of how long it took to purify and sequence a protein or clone and sequence a transcript, 10 or even 5 years ago. Today, scientists can accomplish these goals in weeks! With the recent completion of the Human Genome Project, the emergence of powerful new research technologies, and strong public support for health-related research, the scientific opportunities are seemingly endless, and the challenge becomes choosing wisely among them. I welcome this chance to describe a few of the areas in which NIDCR is making investments—areas that my colleagues and I in the Institute believe offer extraordinary promise for improving oral health. I will also take the opportunity to point out how NIDCR’s activities dovetail with the trans-NIH initiatives termed "Roadmap".

THE NIH ROADMAP

Under the leadership of NIH Director Dr. Elias Zerhouni, NIH as a whole is embarking on an exciting new way to identify and support initiatives that are truly transforming in nature and so significant in scale that no single Institute at the NIH could support the effort alone. Three major areas emerged from a year-long analysis of scientific needs: New Pathways to Discovery, Interdisciplinary Research Teams of the Future, and Re-engineering the Clinical Research Enterprise.

The Roadmap’s New Pathways to Discovery—in particular the initiative Building Blocks, Biological Pathways and Networks—seeks to create a better "toolbox" for researchers that includes innovative ways for capturing real-time images of molecular and cellular events that occur in the human body. The scientific goals of this initiative are closely linked to NIDCR’s molecular anatomy efforts to identify the full complement of genes, proteins, and protein networks expressed in both oral cancer and periodontal disease. Advances in proteomic analysis platforms will be crucial for NIDCR to achieve its goal of defining the salivary proteome—a critical step in the Institute’s long-term goal to exploit salivary secretions for diagnostic purposes. The Molecular Libraries and Molecular Imaging initiative holds great promise for accelerating NIDCR’s progress in defining the molecular pathways of pain reception and in elucidating new therapeutic targets to manage chronic pain. The availability of more robust molecular libraries and facile screening assays will revolutionize our ability to dissect the complex cascade of molecular events responsible for the development of the craniofacial complex, using a chemical genomics approach.

The Roadmap Initiative Research Teams of the Future will stimulate new mechanisms to facilitate the conduct of interdisciplinary research. NIDCR’s work—particularly in areas such as Sjögren’s syndrome, temporomandibular muscle and joint disorders, cleft lip and palate, ectodermal dysplasia, cancer, chronic pain, and infectious diseases—has traditionally included researchers from many disciplines, such as immunology, microbiology, neurobiology, and pain research. Ongoing studies, designed to determine the linkages between oral infections and systemic conditions such as preterm birth and cardiovascular events, have required collaborations among physicians, dentists, and nurses. By integrating several disciplines and their approaches in a more sustained and systematic way, this Roadmap Initiative will enable NIDCR’s ongoing inter- and multidisciplinary efforts to expand and develop new ways to approach research questions.

The Initiative on Re-engineering Clinical Research will promote the integration of academic centers working on clinical research that includes community-based health-care providers. The integration of dentists into this new clinical research infrastructure is key, given that overall health and oral health are interrelated and that certain systemic conditions—such as diabetes, Sjögren’s syndrome, HIV/AIDS, and osteoporosis—have important oral symptoms, manifestations, or complications. NIDCR is creating an oral health practice-based network to support research that answers questions facing dentists in the routine care of their patients and that accelerates the transfer of research findings into practice. In time, linking the oral health practice-based research networks with existing medical networks supported through the Roadmap Initiative will provide additional patients, professional expertise, and integration of resources for conducting research across a broad spectrum of health-care specialties.

NIDCR INVESTMENTS

Clinical Research
Our investments in basic research must go hand in hand with support of clinical and translational research if we are to achieve our ultimate mission of improving people’s health. I am convinced that we can do a better job of translating fundamental knowledge into improvements in clinical practice and oral health. That is why the NIDCR is increasing support for all forms of clinical research. To advance our efforts, we have revised the Institute’s clinical trials program to focus on definitive, multi-center Phase III clinical trials—the kind of research that can provide an evidence base for health policies and standards of care. We also have recently launched an initiative for practice-based research networks. There are many practical questions that require study in a "real-world" environment. Practitioners around this nation could help provide much-needed evidence to better inform approaches to improving oral health. A major Roadmap Initiative will be to integrate existing Clinical Research Networks around the country. We need to assemble practice-based research networks rapidly to ensure that oral health is integrated into medical research networks throughout the Nation.

Tissue Engineering and Nanomedicine
With considerably more knowledge about the basic biology of oral and craniofacial tissues, it will one day be possible to engineer replacement tissues that perform as well as natural bone, muscle, nerves, and other tissues. To further this potentially high-yield area of research, the NIDCR is investing heavily in regenerative medicine. Stem cell biology, while still in its infancy, holds one likely key. Deciduous teeth offer a particularly intriguing source of stem cells that our investigators will exploit to create biological solutions to the restoration of function and form in the craniofacial complex. Biological engineering will one day provide the nanotools required to switch pain signals off in chronic pain situations or dysregulate the quorum sensing required to form dental biofilms. Biological engineering will also yield a remodeling of the cell surfaces to render malignant cells more susceptible to powerful new, and highly specific, therapeutics.

Real-time Health Surveillance
Rather than detecting disease after the fact, real-time health surveillance would allow us to detect early markers of disease rapidly and intervene much sooner. That is the goal of the salivary diagnostics research being pursued by the NIDCR. Scientists have long recognized that saliva serves as a mirror of health, in that it contains the full repertoire of proteins, hormones, antibodies, and other analytes frequently measured in blood tests. The NIDCR is undertaking a major research effort to develop the technologies to create a comprehensive catalog of all proteins found in the saliva of healthy people. Knowledge gained from this salivary proteome project will be invaluable to efforts to develop an artificial salivary gland that mimics the function of natural glands. It also sets the stage for functional studies of salivary secretory components. We envision that these investments could one day lead to miniature "labs on a chip" used to monitor an individual’s health and detect changes that could signal the beginnings of disease.

Oral-Systemic Connections
Research has uncovered associations between oral infections—primarily periodontal disease—and diabetes, heart disease, stroke, and poor birth outcomes. The next step is to resolve the question of whether oral infections cause or contribute to the development of these systemic problems. To that end, the NIDCR is supporting two, multi-center, clinical trials to learn if treating periodontal disease during the second trimester of pregnancy lowers the rate of preterm delivery and increases the birth weight of premature infants. An intervention that lowers the incidence of high-risk births would have a tremendous public health impact. The Institute is also funding a pilot study of heart patients that may ultimately lead to a randomized clinical trial to determine whether periodontal treatment can reduce the occurrence of myocardial events.

Transforming Dental Practice
Our collective goal is to move from the current surgical model of dental practice to a chemotherapeutic or biotherapeutic model. Instead of waiting for caries to become clinically obvious, we need tools that allow us to identify people at high risk and diagnose their disease very early. Instead of removing carious tooth substance, we need treatments that enable us to reverse early disease, such as remineralization agents for incipient caries. And instead of managing bone and connective tissue damage from periodontal infections, we need strategies for preventing the attachment and colonization of disease-causing bacteria in the first place. The NIDCR is pursuing a research agenda designed to lead to better diagnostics and therapeutics. Fueled by the completion of several bacterial genomes, we continue to support many investigations on the nature of bacteria-host cell interactions. Quorum sensing, antimicrobials based on salivary proteins and other naturally occurring substances, and the use of nanomedicine as antimicrobials will play an increasingly important role.

Researchers for the New Era
To ensure the future of oral health research, we must encourage young people to pursue careers in science, and we must develop research-oriented academic environments that cultivate the intellectual talent for research. At NIDCR, we are devoting considerable effort to helping dental schools strengthen their research infrastructure. Our support allows schools to assess their research infrastructure needs and to develop and implement plans to improve them. The schools can use NIDCR funds to hire, support, and mentor investigators; to recruit outstanding scientists; to re-train senior scientists as needed; and to provide a well-organized biomedical research environment that includes technical support staff, equipment, supplies, shared resources, and linkages within and among institutions.

CONCLUSIONS

These are some of the areas in which our collective investment of resources and talent can pay off handsomely in terms of oral health improvements. I encourage you to take a look at NIDCR’s new strategic plan (http://www.nidcr.nih.gov/about/strat-plan/) for a more detailed picture of our research agenda for the next few years. Your feedback, pro and con, is always most welcome (Lawrence.Tabak{at}nih.gov). My colleagues and I at NIDCR urge you to help us invent a future in which all people truly enjoy good health.

ACKNOWLEDGMENTS

I acknowledge, with many thanks, the essential contributions made by my colleagues at NIDCR to achieve the goals of the NIDCR.

Received for publication January 13, 2004. Accepted for publication January 15, 2004.

Journal of Dental Research, Vol. 83, No. 3, 196-197 (2004)
DOI: 10.1177/154405910408300301


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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Tabak, L. A. Search for Related Content PubMed PubMed Citation Articles by Tabak, L. A. Social Bookmarking                         What's this?