American Recovery and Reinvestment Act of 2009

NIH Challenge Grants in Health and Science Research
(RFA-OD-09-003)

National Institute of Dental and Craniofacial Research

NIH anticipates funding 200 or more grants, each of up to $1 million in total costs, pending the number and quality of applications and availability of funds. In addition, Recovery Act funds allocated to NIH specifically for comparative effectiveness research (CER) may be available to support additional grants.  Projects receiving these funds will need to meet this definition of CER: “a rigorous evaluation of the impact of different options that are available for treating a given medical condition for a particular set of patients. Such a study may compare similar treatments, such as competing drugs, or it may analyze very different approaches, such as surgery and drug therapy.” Such research may include the development and use of clinical registries, clinical data networks, and other forms of electronic health data that can be used to generate or obtain outcomes data as they apply to CER.

The application due date is April 27, 2009.

Broad Challenge Areas and Specific Challenge Topics

Note: Those marked with an asterisk (*) are the highest priority topics; however, applicants may apply to any of the topics.

For NIDCR, the Challenge Topics are:

(01) Behavior, Behavioral Change, and Prevention

01-DE-101         Mechanisms of Behavior Change Research
Understanding how behavior change happens, and how and for whom behavioral interventions work, are key components of a strong science of oral health behavior.  Goal:  Research is encouraged that identifies and tests the mechanisms of behavior change related to oral health.  Basic science studies are encouraged that identify the mechanisms underlying the initiation and maintenance of oral health behaviors, and the mechanisms of action of behavioral interventions targeting oral health, across a variety of populations.  Responsive studies include, but are not limited to, laboratory-based studies testing the causal relationships between hypothesized key variables; analysis of archived or existing observational and/or self-report data testing mechanisms of action hypotheses; and enhancement of ongoing intervention studies with additional assessments or methods that allow for mechanisms of action tests. Contact: Dr. Melissa Riddle, 301-451-3888, riddleme@mail.nih.gov


01-DE-102        Behavioral and Social Intervention Research
Studies are encouraged that develop behavioral interventions for oral health.  Goal:  For populations for which data suggest tailored interventions are needed, adaptation and testing of tailored behavioral interventions is appropriate.  For populations for which data do not identify a need for tailoring, testing of evidence-based behavioral interventions is encouraged.  For populations for which inadequate data are available, collection of foundational data followed by intervention development and/or testing would be responsive. Contact: Dr. Melissa Riddle, 301-451-3888, riddleme@mail.nih.gov

(02) Bioethics

02-OD(OSP)-101*     Unique Ethical Issues Posed by Emerging Technologies
Advances in biotechnology and biomedical science raise novel ethical, legal, and social issues. Research in this area is needed to understand the unique ethical concerns related to emerging technologies (e.g. biotechnology, tissue engineering, nanomedicine, and synthetic biology).  These include issues such as dual use research, privacy, safety, intellectual property, commercialization and conflict of interest, among others. Research is also needed to assess how these novel issues are addressed under current oversight and regulatory structures and identify where there may be gaps and/or need for revised or new oversight approaches. OD(OSP) Contact:  Abigail Rives, 301-594-1976, rivesa@od.nih.gov; NIDCR Contact: Dr. Nadya Lumelsky, 301-594-7703, Nadya.Lumelsky@nih.gov

02-OD(OSP)-102*     Ethical Issues in Health Disparities and Access to Participation in Research
Research is needed to assess the under-representation in biomedical and clinical research of U.S. minority populations, underserved populations, and populations who may be vulnerable to coercion or undue influence, to identify barriers to participation in research and to develop approaches for overcoming them. Additionally, studies are needed to assess the impact and ethical considerations of conducting biomedical and clinical research internationally in resource-limited countries.  OD(OSP) Contact:  Abigail Rives, 301-594-1976, rivesa@od.nih.gov; NIDCR Contact: Dr. Ruth Nowjack-Raymer, 301-594-5394, nowjackr@nidcr.nih.gov and Dr. Melissa Riddle, 301-451-3888, riddleme@mail.nih.gov

02-OD(OSP)-103*     Ethical Issues Associated with Electronic Sharing of Health Information
The development of an electronic health information infrastructure and the sharing of health information for patient care and research offer enormous promise to improve health care and promote scientific advances.  However, the broad sharing of such data raises numerous ethical issues that may benefit from additional studies (e.g. those related to privacy and confidentiality).  Examples include studies to assess risks associated with health information technology and the broad sharing of health information for research, and novel approaches for mitigating them. Examination could also include analysis of current oversight paradigms and suggestions for enhancements, as well as assessments of how privacy risks may change in the future. OD(OSP) Contact:  Abigail Rives, 301-594-1976, rivesa@od.nih.gov; NIDCR Contact: Dr. Emily Harris, 301-594-4846, harrisel@nidcr.nih.gov

02-OD(OSP)-104*     Ethical Issues in the Translation of Genetic Knowledge to Clinical Practice
Genetics and genomics have great promise for the development of personalized medicine, yet the ethical, legal and social implications of both the research and application of genetic and genomic knowledge and technology are far reaching. Studies are needed to better understand the factors that influence the translation of genetic information to improved human health and the associated ethical issues. Examples of studies include those to address ethical issues related to broad sharing and use of new genetic information and technologies for research to improve human health, human subjects protection in genetic and genomic research, the identifiability of genetic/genomic information and how our understanding of identifiability is evolving, return of research results and incidental findings to subjects, alternative models of informed consent for broad data sharing for research, and the impact of intellectual property (IP) issues on development of new technologies.  OD(OSP) Contact:  Abigail Rives, 301-594-1976, rivesa@od.nih.gov;  NIDCR Contact: Dr. Emily Harris, 301-594-4846, harrisel@nidcr.nih.gov

02-OD(OSP)-105*     Ethical Issues Raised by the Blurring between Treatment and Research
The distinction between clinical practice and research is growing less clear, a trend that may be more pronounced with respect to genetic information and medical records research. Studies are needed to better understand the ethical issues associated with this trend.  Examples of studies include those to identify how this blurring in roles affects traditional human subjects protections, including, for example, essential practices such as informed consent, conceptions of the doctor/patient and investigator/subject relationship, and privacy protections.  OD(OSP) Contact:  Abigail Rives, 301-594-1976, rivesa@od.nih.gov; NIDCR Contact: Dr. Jane Atkinson, 301-435-7908, Jane.Atkinson@nih.gov

(03) Biomarker Discovery and Validation

03-DE-101       Development, Refinement, or Validation of Biomarkers Relevant to Oral or Craniofacial Disorders
Clinical trials evaluating treatments for oral diseases such as periodontal disease or autoimmune salivary gland diseases are well suited to complementary biomarker studies.  Biofluids such as parotid saliva or gingival crevicular fluid can be collected using non-invasive techniques.  Goal:  Identification of biomarkers from oral fluids, validation against other biofluids or bioassays, and development of diagnostic platforms to predict, diagnose or profile oral and systemic health, and to determine if therapeutic interventions are impacting the biological target.  Other biomarker studies of interest to NIDCR include those seeking to define novel pain biomarkers, biomarkers associated with stress-related responses, and objective and quantifiable measures of pain severity that are independent from self-report based instruments. Contact: Dr. Jane Atkinson, 301-435-7908, Jane.Atkinson@nih.gov

(04) Clinical Research

04-DE-101        Clinical Outcomes of Dental Procedures
Many approaches are used to treat oral diseases and conditions.  The long term successes of different treatment and restorative approaches have not been assessed completely, particularly in patients with complex medical problems or rare dental diseases.  Goal: Assessment of the comparative effectiveness of diagnostic technologies with differing costs, or cost-effectiveness of new and innovative interventions; cost-effectiveness or comparative effectiveness of existing interventions with demonstrated effectiveness, including in patients with compromised oral health such as those having undergone head and neck radiation, Sjögren’s syndrome or rare syndromes such as the Ectodermal Dysplasias. Contact: Dr. Jane Atkinson, 301-435-7908, Jane.Atkinson@nih.gov

04-DE-102       Classification Criteria for Craniofacial Diseases
New classification criteria have been proposed for genetic diseases that significantly impact the oral structures, but validation studies are needed to establish their utility.  Goal: Refinement or validation of current classification criteria for rare genetic diseases with significant oral and craniofacial manifestations. Contact: Dr. Jane Atkinson, 301-435-7908, Jane.Atkinson@nih.gov

04-DE-103        Feasibility of Evaluating Effectiveness Using Current Infrastructure
There is a limited evidence base to support common interventions in dental care and management options in craniofacial disorders. It is not certain to what degree the current infrastructure can support evaluation of effectiveness in oral health or craniofacial conditions. Goal:  Assessment of, or demonstration of the usefulness of current infrastructure for evaluating the effectiveness of prevention or treatment approaches in oral health or craniofacial conditions. Contact: Dr. Jane Atkinson, 301-435-7908, Jane.Atkinson@nih.gov

04-DE-104     Survival of Resin Dental Composites
Resin dental composites are one of the most frequently used materials for restoration of teeth.  Multiple formulations are available commercially.  The long-term outcomes of different composite materials have not been compared extensively.  For example, resin dental composite shrinkage is implicated as the main cause of failure of dental restorations. However, this hypothesis has not been clinically evaluated by comparing outcomes of low shrinkage and high shrinkage resin composite restorations. Studies allowing survival comparisons of different resin dental composites are encouraged.   This could be accomplished by examining patients treated previously, or through analyses of records that indicate the type of resin material used for restoration.  NIDCR Contact: Dr. James Drummond, 301-402-4243, drummondj@nidcr.nih.gov

(05) Comparative Effectiveness Research

05-DE-101*    Validating dental caries risk assessment guidelines
Traditionally, dental caries is prevented and managed with surgical restoration of damaged teeth and by recalling patients at regular six-month intervals.  New strategies propose tailoring dental caries management to the individual’s risk for dental disease.  However, proposed caries risk assessment approaches have not been validated extensively. Projects that answer this challenge could include planning projects for large-scale definitive clinical trials or sophisticated analyses of existing datasets or records.  NIDCR Contact: Dr. Ruth Nowjack-Raymer, 301-594-5394, nowjackr@nidcr.nih.gov

05-DE-102*     Treatment of tobacco and drug dependence in dental settings
Use of tobacco and other drugs is a major culprit in oral diseases. The dental office provides a potentially important entry point for supporting drug-abusing patients in cessation efforts. However, busy dental practices may have difficulty finding the resources, staff, training time, and patient acceptance to incorporate comprehensive drug abuse treatment into clinical practice. Approaches that involve Screening for drug use, Brief Intervention, and Referral to Treatment (SBIRT) provide a promising, practical solution. Studies in other busy clinical settings have found that simple provider-delivered and computer-assisted SBIRT approaches increase identification of drug use, and importantly, increase cessation rates. Similar studies are needed in the dental setting comparing provider-delivered substance abuse SBIRT to computer-assisted SBIRT for tobacco use, or abuse of alcohol or other drugs. Projects that answer this challenge could include proposals to design and pilot a randomized clinical trial comparing different therapies in the dental setting. Applicants would need to submit a future NIDCR Clinical Trial Implementation grant for support of any proposed clinical trials, which could be considered for support through regular NIDCR appropriated funds. NIDCR Contact: Dr. Melissa Riddle, 301-451-3888, riddleme@nidcr.nih.gov

05-DE-103*    Treatment and Outcomes Cleft Palate/Cleft Lip Anomalies
Cleft lip and/or palate are among the most common of all birth defects, occurring once in every 600 to 800 births.  The care of affected infants is complex and requires coordination with surgeons, orthodontists, dentists, surgical support staff, speech therapists, audiologists, and other specialists.  Surveys of care centers in the United States and Europe demonstrate that there are enormous variations in timing and type of reconstruction procedures.  Practices associated with best outcomes need to be identified. Projects that answer this challenge could address: (1) Presurgical appliances, whether to use and what type (NAM or Latham); (2) Surgical timing, at what age to repair unilateral and  bilateral cleft lip and with what technique; (3) Use of lip adhesion and indication for its use; (4) Cleft palate repair technique and timing of repair.  Investigators could compare existing approaches to repair of cleft lip and cleft palate, evaluating efficacy, cost effectiveness, speech outcomes and quality of life measures.   Approaches could include:   1) establishment of observational patient registries to follow outcomes and identify best practices; or 2) planning grants for a definitive RCT or practical trial to address a significant issue.  Applicants would need to submit a future NIDCR Clinical Trial Implementation grant for support of any proposed clinical trials, which could be considered for support through regular NIDCR appropriated funds. Contact: Dr. Holli Hamilton, 301-451-3852, hamiltonho@nidcr.nih.gov

05-DE-104*    Adjunctive techniques for detection of oral premalignant and malignant lesions
Approximately 35,000 Americans are diagnosed each year with oral cancer, and early detection, usually during a regular dental check-up, is critical to successful treatment of this disease. Adjunctive techniques have been developed to enhance visual detection of oral premalignant and malignant lesions. Overall, there is insufficient evidence to support their effectiveness.  Projects that answer this challenge could include planning for randomized clinical trials that compare visual and tactile oral mucosal examination with adjunct-assisted examination in dental settings. Projects responsive to this challenge could estimate the effectiveness of existing adjunctive techniques for detection of oral premalignant and malignant lesions from available datasets or records, including cost effectiveness analyses.  Applicants would need to submit a future NIDCR Clinical Trial Implementation grant for support of any proposed clinical trials, which could be considered for support through regular NIDCR appropriated funds. Contact: Dr. Jane Atkinson, 301-435-7908, jatkinso@nidcr.nih.gov

05-DE-105*    Infrastructure for Comparative Effectiveness Studies in Oral Health and Craniofacial Conditions
There is a limited evidence base to support common interventions in dental care and management options in craniofacial disorders. Having adequate infrastructure for evaluating effectiveness in oral health and craniofacial conditions, as distinguished from effectiveness in medical care, is critical because much of oral health care is delivered outside of medical care (e.g., dental offices) or fragmented to address the complex needs of individuals with certain conditions affecting oral/craniofacial structures (e.g., birth defects such as cleft lip and palate, ectodermal dysplasias, or conditions resulting in hypodontia).  Projects that answer this challenge could support planning grants to develop infrastructure as well as feasibility studies to assess existing infrastructure.  Support for planning grants to develop infrastructure will be provided, as well as support for feasibility studies to assess existing infrastructure. Successful two-year projects may lead to applications to: implement and assess infrastructure (e.g. development of datasets or registries); enhance and re-assess existing infrastructure; or conduct comparativeness effectiveness studies. Contact: Dr. Emily Harris, 301-594-4846, harrisel@nidcr.nih.gov

(06) Enabling Technologies 

06-DE-101        Imaging of Oral Diseases
High resolution imaging modalities with enhanced specificity and sensitivity can be powerful tools for early detection of oral diseases, and for monitoring of treatment outcome.  Goal: Development, refinement or testing of novel imaging modalities for the early detection of oral and dental lesions, including but not limited to oral squamous cell carcinoma, demineralized tooth surface, or alveolar bone loss or necrosis.  Development of non-invasive or minimally-invasive approaches for the early detection, diagnosis, and measurement of response to treatment of diseases that are currently difficult to diagnose, detect, or treat. Contact: Dr. Yasaman Shirazi, 301-594-4812, Yasaman.Shirazi@nih.gov

06-DE-102        Structural and Molecular Atlases of Craniofacial Development
Craniofacial developmental processes are complex events that set up temporal and spatial tissue morphogenetic boundaries.  Although much work has contributed to our knowledge base, a comprehensive high resolution map of the morphogenetic template has not been accomplished.  Goal: Development of high resolution imaging of developmental processes and development of markers and probes to track normal and abnormal developmental processes at the single cell level for the construction of structural and molecular atlases of craniofacial development that will be shared through FaceBase. Contact: Dr. Lillian Shum, 301-594-0618, Lillian.Shum@nih.gov

06-DE-103        Novel Technologies for Cultivation of Oral Microbes
Recent molecular studies reveal that nearly 800 taxa comprise the human oral microbiome.  Initial identification of un-named phylotypes, and in many cases not-yet cultivated species or those incapable of in vitro growth, has been accomplished primarily through metagenomic studies.  While metagenomics can indicate the presence of particular organisms, direct laboratory examination via cultivation ultimately will be needed.  Goal:  Development of new methods and technologies to allow for in vitro growth of organisms refractory to standard microbiological cultivation, including co-cultivation, domestication, and identification of host-derived nutrients for morphological analysis and classical biochemical and metabolic characterization. Contact: Dr. R. Dwayne Lunsford, 301-594-2421, lunsfordr@nidcr.nih.gov

06-DE-104       Click Chemistry for Oral, Dental and Craniofacial Applications
“Click chemistry” was coined in 2001 by Barry Sharpless and colleagues to describe a synthetic chemical method to link simple organic molecules together through highly efficient, highly selective, and non-toxic reactions.  Currently, the centerpiece of click chemistry is a reaction to connect building block molecules that can occur at physiological temperatures in aqueous medium.  This reaction has proven useful for: developing reporters and tags for DNA, proteins, and carbohydrates in vivo through bioconjugation; developing protease inhibitors or a spectrum of anti-infective and anti-tumor agents; creating molecular libraries; synthesizing novel polymer materials; and functionalizing material surfaces for microarray, biosensor or microfluidic platforms.  Goal:  Application of “click chemistry” for oral, dental and craniofacial applications, including but not limited to the development of small molecules to disrupt oral biofilms or anti-infective agents for oral diseases, head and neck cancer detection agents and therapeutics, new dental materials, or novel in vivo molecular imaging modalities. Contact: Dr. Lillian Shum, 301-594-0618, Lillian.Shum@nih.gov

06-DE-105       Oral Fluid-based Point-of-care Diagnostic Platforms
Cataloging the salivary proteome is a significant first step toward understanding how salivary protein levels and states may provide a profile of oral and systemic health and disease.  Many of these proteins already serve as biomarkers in lab-based bioassays of various bodily fluids.  Goal:  Using a targeted approach, development and validation of these bioassays for adaptation to oral fluid-based point-of-care diagnostic platforms. Contact: Dr. Lillian Shum, 301-594-0618, Lillian.Shum@nih.gov

06-DE-106        Real Time Feedback of Changing Conditions of Oral and Systemic Health
Continuous measurement and monitoring of physiological variables face major challenges in the home setting for patients and especially for infants and the elderly.  Non-invasive, non-restrictive health monitoring devices would allow continuous evaluation of an individual’s current health to provide immediate patient awareness of changing conditions that could be corrected before entering a detrimental phase.  Goal:  Development of proof-of-concept biosensor wearable in the oral cavity for continuous and dynamic monitoring of changing conditions of oral and systemic health to allow immediate feedback. Contact: Dr. James A. Drummond, 301-402-4243, drummondj@nidcr.nih.gov

06-DE-107       Technologies to Facilitate Oral Health Behaviors
New or adapted technologies provide opportunities to enhance oral health behavior, and allow for flexible delivery of evidence-based oral health behavioral interventions, without extensive staff time or training.  Goal:  Studies are encouraged that develop (or adapt) and test technologies to enable oral health behavior assessment, monitoring and/or intervention. Research is also encouraged that tests technologies to measure physiologic, behavioral, and social factors demonstrated to be important in oral health (e.g., novel measures of adherence to care-provider recommendations, remote monitoring of oral hygiene and nutrition practices, reliable and valid remote measures of tobacco use). Contact: Dr. Melissa Riddle, 301-451-3888, riddleme@mail.nih.gov

(07) Enhancing Clinical Trials 

07-DE-101       Enhancing Clinical Trials
Data capture in clinical trials is costly and time-consuming, and subject adherence can be difficult to monitor.  Goal: Improvement of methods to enhance automated full capture of oral health status and dentist-patient interactions would greatly benefit clinical trials for oral diseases, oral health research and practice-based research conducted in private dental practice settings.  This would include affordable technologies to enable: remote capture of oral health measures, study medication compliance and adverse event monitoring. Contact: Dr. Jane Atkinson, 301-435-7908, Jane.Atkinson@nih.gov

(08) Genomics

08-DE-101 *     Planning Grants for Genome-wide Studies of Understudied Oral and Craniofacial Diseases and Disorders [Temporomandibular Joint Disorder, Oral Cancer, Sjögren’s Syndrome, Periodontal Disease]
Genome-wide studies have yielded significant insights into the genetic etiologies of many common complex diseases, but this approach has not been widely adopted for highly complex oral and craniofacial diseases such as TMJ disorder, oral cancer, Sjögren’s syndrome, or periodontal disease.  Goal: Assessment of the adequacy and consistency of clinical, risk factor, endophenotype, behavioral and demographic data of participants from different research groups; adequacy of tissue specimens for genome-wide technologies; and feasibility of the initial genome-wide study and follow-up studies. [High Priority Topic for NIDCR.]  Contact: Dr. Emily Harris, 301-594-4846, harrisel@nidcr.nih.gov

08-DE-102        Measurement of Behavioral and/or Social Factors in GEI Studies
The quality of Gene-by-Environment Interaction Studies (GEI) depends in large part on the quality of measures of the environmental influences on health.  Goal:  Studies are encouraged that develop measures, assessments and/or methods that capture the environmental factors (e.g., behavioral, social) hypothesized to interact with genetic influences on oral health or craniofacial disorders. Contact: Dr. Melissa Riddle, 301-451-3888, riddleme@mail.nih.gov

08-DE-103          Epigenomics and Epigenetics of Oral Health and Disease
The maintenance of health and susceptibility to disease are, in part, the result of epigenetic regulation of the genetic blueprint.  Epigenetic/epigenomic regulation of gene transcription is an emerging frontier of science that directs functional processes in development across the lifespan as well as in disease states.  Goal:  Elucidation of the epigenetics/epigenomics basis and environmental influences on the molecular mechanisms underlying the susceptibility, development, progression and resolution of oral, dental and craniofacial diseases and conditions, including but not limited to craniofacial disorders, head and neck cancer, periodontal disease, Sjögren’s syndrome, orofacial pain; elucidation of the epigenetic/epigenomic regulation of orofacial stem and progenitor cells; production of epigenome-wide information for the identification and characterization of therapeutic targets and predictive biomarkers. Contact: Dr. Emily Harris, 301-594-4846, harrisel@nidcr.nih.gov

08-DE-104    Genotyping of Existing Cohorts in Craniofacial, Dental, and Oral Conditions
These studies will utilize existing clinical cohorts to add to the broadly shared data resources available to genetic researchers. The immediate result of the work will be the submission of large genotype-phenotype datasets to the database of Genotypes and Phenotypes (dbGaP) (http://www.ncbi.nlm.nih.gov/sites/entrez?db=gap). This is expected to allow the submitting investigators and others to pursue analytical projects that will identify genetic loci contributing to disease risk. The datasets will also provide a testing ground for new methodological approaches for the identification of genetic risk factors. Medical sequencing, fine-mapping, and replication studies are included, but recruitment of new cohorts is not. Contact: Emily Harris, 301-594-4846, harrisel@nidcr.nih.gov

(09)  Health Disparities

09-DE-101        Behavioral and Social Sciences to Reduce Oral Health Disparities
Many ongoing studies seek to determine if behavioral and social science approaches can reduce health disparities in the U. S. population.  These projects often test interdisciplinary approaches to change health behaviors. Oral health messages could be incorporated into these programs.  Goal:  Basic behavioral and/or social sciences research is encouraged that identifies specific, mutable, causal factors responsible for disparate oral disease or oral health outcomes in specific populations.  Applied behavioral and/or social sciences research is encouraged that develops or adapts and tests interventions to reduce hypothesized causes of oral health disparities in specific populations.  For intervention studies, applicants need to provide a strong justification for the need to develop a new behavioral or social intervention, e.g., providing evidence that an existing intervention is not adequate for the target population, or providing a compelling rationale for why an existing intervention does not address the causes of oral health disparities.  Populations of particular interest include racial or ethnic minority populations, economically disadvantaged communities, those in rural geographic areas, older adults with complex medical conditions, institutionalized individuals, etc. Contact: Dr. Ruth Nowjack-Raymer, 301-594-5394, ruth.nowjack-raymer@nih.gov

(10) Information Technology for Processing Health Care Data for Research

For this RFA, there is no NIDCR-specific Challenge Topic in this Challenge Area.

(11)  Regenerative Medicine

11-DE-101         Craniofacial Tissue Regeneration
Every hour, a baby is born with a craniofacial birth defect that requires complex surgical correction.  In addition, numerous procedures are performed each year for maxillofacial reconstruction following head and neck cancer surgery, and trauma and injuries from accidents, violence, and, more recently, combat.  Technological advances present the timely research opportunity to promote craniofacial tissue regeneration using bioengineering and biomimetic approaches.  Goal:  Design of strategies to promote craniofacial tissue regeneration using bioengineering and biomimetic approaches, including the development of novel biomaterials and scaffolds, directed differentiation of stem and progenitor cells, modulation of mechanical and other physical properties of tissues to guide their morphogenesis, control of the wound healing microenvironment, tissue printing and local delivery of therapies. Contact: Dr. Nadya Lumelsky, 301-594-7703, Nadya.Lumelsky@nih.gov 

(12) Science, Technology, Engineering and Mathematics (STEM) Education

For this RFA, there is no NIDCR-specific Challenge Topic in this Challenge Area.

(13) Smart Biomaterials - Theranostics

13-DE-101*         Novel Self-Healing Smart Dental and Bio-Restorative Materials
Dental materials and other biomaterials have limited survival when placed in the human body.  Goal:  Development of a new generation of “self-healing” and “smart” dental and bio-restorative materials that can diagnose structural failure and repair themselves to minimize the loss of natural structures associated with materials failure.  These new materials can also be designed with properties to survive in extreme and adverse conditions, such as in patients with xerostomia. Contact: Dr. James A. Drummond, 301-402-4243, drummondj@nidcr.nih.gov

13-DE-102           Dental Resin Composites and Caries
Half of all dental restorations fail within 10 years, and replacing them consumes 60% of the average dentist’s practice time.  Dental materials are challenged by the harsh mechanical and chemical environment of the oral cavity with secondary decay being the major cause of failure.  Goal:  Development of stronger and longer-lasting biocompatible dental restorations by engineering novel dental materials or new resin systems, enhancing existing materials, and incorporating bioactive agents in materials to combat microbial destruction and to sustain the harsh mechanical and chemical environment of the oral cavity. Contact: Dr. James A. Drummond, 301-402-4243, drummondj@nidcr.nih.gov

(14) Stem Cells

14-DE-101*        Precise Reprogramming of Cells from Oral and Craniofacial Tissues
Recent advances in reprogramming of somatic cells into induced pluripotent stem cells (iPS) cells constitute an important breakthrough, but the utility of iPS cells for future cell-based therapies is limited by the scarcity of efficient differentiation protocols to guide developmentally primitive iPS cells through a long progression of developmental stages toward fully-differentiated functional somatic cells.  Goal: Development of novel approaches for partial reprogramming of somatic cells of the oral and craniofacial complex (e.g. periodontal ligament cells, pulp cells, oral mucosal cells, salivary acinar cells, fibrocartilaginous cells of the temporomandibular joint) for cell-based therapies to heal and restore these tissues following disease or trauma. Contact: Dr. Nadya Lumelsky, 301-594-7703, Nadya.Lumelsky@nih.gov

14-DE-102          Characterizing the Normal and Pathological Oral Mucosal Stem Cell Niche
Despite efforts in oral cancer research, the molecular and cellular events leading to the initiation and early progression of oral cancer remain elusive.  Notably, the structure and function of the normal oral mucosal stem cell niche that support the regenerative capacity of oral mucosa have not been characterized and the mechanisms of malignant transformation of normal mucosal cells are unknown.  Goal:  Elucidation of the interactions between the stem cell niche, the stromal microenvironment and the immune system that induce and support oral cancer progression and control regeneration of normal mucosa. Contact: Dr. Nadya Lumelsky, 301-594-7703, Nadya.Lumelsky@nih.gov

14-DE-103          Enhancing Human Embryonic Stem (ES) Cell Culture Systems
Cell differentiation and tissue morphogenesis during normal development is guided by the highly orchestrated temporal, spatial and combinatorial action of multiple of ligands, signaling pathways, transcription factors, and extracellular matrices.  In light of this tremendous complexity, the existing human ES cell in vitro culture systems lack appropriate sophistication thus necessitating the need for strategies to better mimic normal developmental processes.  Recent progress in the fields of bioengineering, nanotechnology, biomaterials and bioimaging offer a wealth of tools that can lend tight control of the multiple parameters needed to improve the existing human ES culture systems.  Goal:  Integration of engineering disciplines with developmental biology and with ES cell technology for deriving a new generation of human ES cell culture protocols that will facilitate the application of ES cell-based therapies for the treatment of a multitude of human tissue degenerative diseases and trauma, including those of oral and craniofacial complex. Contact: Dr. Nadya Lumelsky, 301-594-7703, Nadya.Lumelsky@nih.gov

(15) Translational Science

15-DE-101*        Molecular Profiling and Developing Mouse Models for Salivary Gland Tumor Research
The biggest challenge in salivary gland tumor research is the lack of molecular phenotypic characterization of a heterogeneous class of tumors, and the lack of appropriate mouse models for charting the molecular pathogenesis of and testing therapeutic agents for the tumors.  Goal: Initiation of systematic and comprehensive profiling of the genomics, proteomics, epigenomics, metabolomics and glycomics of salivary gland tumors. Informed by this information, develop xenograft models, MMTV-associated transgene models, and transgenic and knock-out gene-disruption models for preclinical testing in mice. Contact: Dr. Yasaman Shirazi, 301-594-4812, Yasaman.Shirazi@nih.gov


15-DE-102*          New Models and Measures in Pre-clinical Chronic Pain Research
Existing animal models of temporomandibular or orofacial pain conditions inadequately reflect the pathology or the phenotypes of the human state. Goal:  Development of new animal models to study the transition from acute to chronic pain in temporomandibular joint disorders or other orofacial pain disorders. Coupled with the development of new functional and behavioral assays of acute and chronic pain, these animals models would be a powerful means to enhance our understanding of the biological mechanisms underlying the development of these chronic pain conditions and the responses of patients to therapeutic interventions. Contact: Dr. John Kusiak, 301-594-7984, John.Kusiak@nih.gov

15-DE-103      Translational Application of Gene Silencing Strategies to Oral and Craniofacial Disorders
The application of oligonucleotide-based methods for modifying gene expression has emerged as a powerful research tool that has vast potential for understanding disease processes and for the development of new therapeutics.  These methods have become widely used based on the ease of designing and testing oligonucleotides for any host gene or pathogen whose nucleic acid sequence is known.  Goal:  Development of translational research by harnessing oligonucleotide-based approaches such as RNA interference (RNAi) to modify the expression of genes associated with oral, dental, and craniofacial diseases and disorders, coupled with technological innovations to improve the efficiency of delivery, specificity, processing or stability of the oligonucleotide-based strategy. Contact: Dr. Yasaman Shirazi, 301-594-4812, Yasaman.Shirazi@nih.gov

15-DE-104       Functional Restoration of Salivary Glands
Saliva is essential for maintaining oral homeostasis; reduction in salivary function causes serious oral disease.  Severe reductions in salivary function occur in patients with Sjögren’s syndrome, an autoimmune exocrinopathy that primarily affects women, and individuals who have had external beam radiation for treatment of head and neck cancers.  Despite a volume of knowledge in the biology and pathophysiology of salivary glands, few breakthroughs have been made to restore salivary gland function; artificial saliva is not a long-term solution.  Goal: Development of cell-, protein/peptide-, small molecule-, and gene-based approaches to stimulate fluid secretion by increasing the activities of channels and transport proteins, or repairing defective acinar and ductal cells in secretory units; development of dynamic tools to reliably examine salivary function. Contact: Dr. Lillian Shum, 301-594-0618, Lillian.Shum@nih.gov

15-DE-105        Pathophysiology of Bisphosphonate-associated Osteonecrosis of the Jaw (ONJ)
Published reports on bisphosphonate-associated ONJ have overwhelmingly focused on the epidemiology, presentation and conservative treatment options of this morbid oral condition, whereas the underlying pathophysiology remains unexplored.  Goal: Elucidation of the underlying pathophysiology and clinical resolution of bisphosphonate-associated osteonecrosis of the jaw, including how bisphosphonates may interfere with bone healing and repair at the genetic, molecular, cellular and tissue levels, and the identification of risk factors, onset, progression and management of this condition in patients. Contact: Dr. Lillian Shum, 301-594-0618, Lillian.Shum@nih.gov

15-DE-106        Developing Oral Topical Formulations for Enhancing Oral Mucosal Defenses and Controlling Oral Infections and Lesions
Ulcerative oral lesions such as necrotizing ulcerative periodontitis, acute necrotizing ulcerative gingivitis, and aphthous ulcers are a major cause of morbidity in patients with a variety of disease conditions. Oral topical formulations of compounds with combined microbicidal, analgesic and anti-inflammatory activities are not currently available to eradicate oral pathogens, inhibit the spread of infections, and alleviate discomfort and inflammation.  Goal:   Development of new oral topical medication formulations to enhance oral mucosal defenses, eradicate oral pathogens, control oral infections and lesions, and alleviate discomfort and inflammation. Contact: Dr. Isaac Rodriguez-Chavez, 301-594-7985, Isaac@nidcr.nih.gov

15-DE-107       Metagenomics of the Oral Microbiome in Health and Disease
Studies have shown that the microbial composition of the oral cavity is highly diverse, and that this composition is dynamically altered during the onset, progression and treatment of oral diseases, such as with dental caries or oral infections in immunocompromised patients with HIV/AIDS, stem cell transplantation, and cancer.  Goal:  Application of metagenomic approaches to characterize the oral microbiomes that are associated with oral diseases and to compare with the core dataset associated with health that is being generated by the Human Microbiome Project, including but not limited to conditions such as dental caries, periodontal diseases, oral manifestation of immunosuppression, and oral complications of cancer therapies. Contacts: Dr. R. Dwayne Lunsford, 301-594-2421, lunsfordr@nidcr.nih.gov (for non-HIV/AIDS component) and Dr. Isaac Rodriguez-Chavez, 301-594-7985, Isaac@nidcr.nih.gov (for HIV/AIDS component)

15-DE-108        Oral Health in HIV/AIDS Patients with Central Nervous System Manifestations
A spectrum of neurologic disorders associated with HIV/AIDS infections, including dementia and pain derived from neuropathies and inflammation, affect between 30% and 70% of infected individuals, even for those on antiretroviral therapy.  These comorbid conditions adversely affect oral health status and adherence to therapies in HIV/AIDS patients; however, the scope of the problem and risk factors for these neurologic disorders have not been identified.  Goal: Determination of: 1) the incidence and prevalence of central nervous system manifestations, generation of pain from neuropathies and inflammation, and oral health status in HIV/AIDS patients in demographically and genetically diverse cohorts; and 2) genetic susceptibility to central nervous system manifestations with oral complications among HIV/AIDS patients. Contact: Dr. Isaac Rodriguez-Chavez, 301-594-7985, Isaac@nidcr.nih.gov

15-DE-109          Novel Immunotherapies to Treat HIV/AIDS-related Oral Manifestations and AIDS Malignancies
While HIV/AIDS-related oral manifestations and AIDS malignancies can be managed, there are few novel immunotherapies in the pipeline that can be developed into effective treatment.  Goal:  Development of novel immunotherapies for modulation of the immune response against HIV-associated oral pathogens and AIDS malignancies through the use of cytokines, chemokines, adjuvants (e.g., neo-adjuvants, nano-adjuvants, and mucosal adjuvants), antibodies and other molecules of the immune system alone or in combination with other treatment modalities. Contact: Dr. Isaac Rodriguez-Chavez, 301-594-7985, Isaac@nidcr.nih.gov


 

For general information on NIDCR's implementation of NIH Challenge Grants, contact:

Dr. Pamela McInnes
Director, Division of Extramural Research
NIDCR
National Institutes of Health 
Phone: 301-443-8618
E-mail: pmcinnes@nidcr.nih.gov  

For Financial or Grants Management questions, contact:

Ms. Mary Daley
Chief Grants Management Officer
NIDCR
National Institutes of Health
Phone:  301-594-4808
E-mail:  md74u@nih.gov