Date: September 15, 2017
Place: Conference Room 10
National Institutes of Health
The 216th meeting of the National Advisory Dental and Craniofacial Research Council (NADCRC) was convened on September 15, 2017, at 8:35 a.m., in Building 31, Conference Room 10, National Institutes of Health (NIH), Bethesda, Maryland. The meeting was open to the public from 8:35 a.m. to 12:15 p.m.; it was followed by the closed session for Council business and consideration of grant applications from 1:40 p.m. until adjournment at 1:52 p.m. Dr. Martha Somerman presided as Chair.
- Dr. Shenda M. Baker
- Dr. Yang Chai
- Dr. Nisha J. D’Silva
- Ms. Tracy Hart
- Dr. Daniel Malamud (via phone)
- Dr. Daniel W. McNeil
- Dr. Phillip B. Messersmith
- Dr. Anne Louise Oaklander
- Dr. Sanjay Shete
- Dr. Anne C. R. Tanner
- Dr. Jane A. Weintraub
Ad Hoc Members
- Dr. David J. Couper
- Dr. Joyce A. De Leo
Members of the Public
- Mr. Shaun R. Abrams, NIDCR trainee, Dentist-Scientist Training Program (DSTP), Oral and Craniofacial Sciences Graduate Program, University of California, San Francisco (UCSF) School of Dentistry, San Francisco, CA
- Dr. Seun Ajiboye, Director of Science Policy and Government Affairs, International Association for Dental Research (IADR)/American Association for Dental Research (AADR), Alexandria, VA
- Dr. Marcelo W. B. Araujo, Vice President, Science Institute, American Dental Association (ADA), Washington, D.C.
- Dr. John R. Bartlett, Associate Dean for Research, The Ohio State University College of Dentistry, Columbus, OH
- Dr. Robert J. Burns, Manager, Legislative and Regulatory Policy, ADA, Washington, D.C.
- Mr. Christopher R. Donnelly, NIDCR trainee, DSTP, Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI
- Ms. Marybeth Francis, NIDCR trainee, DSTP, University of Illinois at Chicago (UIC) College of Dentistry, Chicago, IL
- Dr. Raul Garcia, Professor and Chair, Department of Health Policy and Health Services Research Director, Northeast Center for Research to Evaluate and Eliminate Health Disparities, Boston University Henry M. Goldman School of Dental Medicine, Boston, MA
- Dr. Gregg H. Gilbert, Professor and Chairman, Department of General Dental Sciences, University of Alabama at Birmingham School of Dentistry, and National Network Director, National Dental Practice-Based Research Network, Birmingham, AL
- Dr. Linda M. Kaste, Professor, Department of Pediatric Dentistry, UIC College of Dentistry, Chicago, IL, and Member, Board of Directors, IADR/AADR, Alexandria, VA
- Mr. B. Timothy Leeth, Senior Director for Federal Relations, Advocacy and Government Relations, American Dental Education Association ADEA, Washington, D.C.
- Dr. Felix Liao, Whole Health Dental Center, Falls Church, VA
- Dr. Kalu Ogbureké, Legislative Fellow, ADEA, Washington, D.C.
- Dr. Jeffrey Stewart, Senior Director, Institutional Innovation and Development, Learning Center, ADEA, Washington, D.C.
- Ms. Christina McWilson Thomas, Director for Government Affairs, Advocacy and Government Relations, ADEA, Washington, D.C.
- Dr. Gregory G. Zeller, Clinical director of the electronic health record implementation project, University of Maryland Baltimore College of Dental Surgery, Baltimore, MD
National Institute of Dental and Craniofacial Research
- Dr. Martha J. Somerman, Director
- Dr. Alicia Dombroski, Executive Secretary, and Director, Division of Extramural Activities (DEA)
- Dr. Lillian Shum, Director, Division of Extramural Research (DER)
- Dr. Robert Angerer, Scientific Director, Division of Intramural Research (DIR)
- Dr. John W. Kusiak, Office of the Director (OD), Acting Deputy Director
- Dr. Matthew P. Hoffman, Deputy Scientific Director, DIR
- Dr. Margo Adesanya, OD, Office of Science Policy and Analysis (OSPA), Science Policy and Planning Branch (SPPB)
- Dr. Jane Atkinson, DER, Center for Clinical Research (CCR)
- Dr. Nisan Bhattacharya, DEA, Scientific Review Branch (SRB)
- Ms. Karina Boehm, OD, Office of Communications and Health Education (OCHE)
- Dr. Kathi Buss, OD, OSPA
- Dr. Preethi Chander, DER, Integrative Biology and Infectious Diseases Branch (IBIDB)
- Ms. Vicki Contie, OD, OCHE, Science Communication and Digital Outreach Branch (SCDOB)
- Ms. Michelle Cortes, DER IBIDB
- Ms. Mary Cutting, DER, CCR
- Ms. Mary Daum, OD, OCHE, Health Information and Public Liaison Branch (HIPLB)
- Mr. Bret Dean, OD, Office of Administrative Management (OAM), Financial Management Branch (FMB)
- Ms. Aachal Devi, OD, OSPA
- Dr. Bruce Dye, OD, OSPA
- Dr. Olga Epifano, DEA
- Dr. Catherine Evans, OD, OCHE, SCDOB
- Dr. Dena Fischer, DER, CCR
- Dr. Leslie Frieden, DEA, Research Training and Career Development Branch (RTCDB)
- Dr. Crina Frincu, DEA, SRB
- Dr. Gallya Gannot, DER, CCR
- Dr. Nicole Garcia-Quijano, OD, OCHE, HIPLB
- Mr. Joel Guzman, DER, Translational Genomics Research Branch (TGRB)
- Dr. Emily Harris, DER, TGRB
- Mr. Gabriel Hidalgo, DEA, Grants Management Branch (GMB)
- Dr. Jonathan Horsford, OD, OSPA
- Dr. Timothy Iafolla, OD, OSPA
- Dr. Chandrashekar Janakram, OD, OSPA
- Dr. Lynn Mertens King, DEA, RTCDB
- Dr. Wendy Knosp, OD, OSPA
- Ms. Carol Loose, OAM, FMB
- Mr. Orlando Lopez, DER, IBIDB
- Dr. Nadya Lumelsky, DER, IBIDB
- Dr. R. Dwayne Lunsford, DER, IBIDB
- Ms. Jayne Lura-Brown, DER
- Dr. Kevin McBryde, DER
- Dr. Marilyn Moore-Hoon, DEA, SRB
- Dr. Dawn Morales, DER, Behavioral and Social Sciences Research Branch (BSSRB)
- Ms. Anna Nicholson, OD, Office of Clinical Trials Operations and Management (OCTOM)
- Dr. Morgan O’Hayre, OD
- Ms. Ann Poritzky, OCHE, SCDOB
- Mr. John Prue, OD, Office of Information Technology (OIT)
- Dr. Melissa Riddle, DER, BSSRB
- Ms. Delores Robinson, DEA
- Dr. David Schindler, OD, OSPA
- Dr. Steven Scholnick, DER, TGRB
- Mr. Don Seymour, OD, OIT
- Dr. Yasaman Shirazi, DEA, SRB
- Mr. Matthew Sierra, OD, FMB
- Dr. Kathryn Stein, DER, TGRB
- Ms. Kathleen Stephan, OD
- Mr. Joseph Tiano, OD, OSPA
- Dr. Yolanda Vallejo-Estrada, DER, IBIDB
- Dr. Justin Vos, OD, OSPA
- Dr. Jessica Walrath, OD, OSPA
- Dr. Jason Wan, DER, IBIDB
- Dr. S. Chiayeng Wang, DER, IBIDB
- Dr. Darien Weatherspoon, DER, CCR
- Dr. Gary Zhang, DEA, SRB
Other Federal Employees
- Dr. Bonnie J. Mathieson, Office of AIDS Research, Office of the Director, NIH
I. WELCOME AND INTRODUCTIONS
Dr. Martha Somerman, Director, NIDCR, called the 216th meeting of the Council to order. She thanked the Council members for their service and welcomed everyone, including the Council, guests, and participants attending via the NIH videocast (http://videocast.nih.gov). She especially thanked those who traveled from places affected by the recent hurricanes in Florida and Texas.
Dr. Somerman noted that the terms of three Council members are expiring. She thanked Dr. Anne Louise Oaklander, Dr. Anne C. Tanner, and Dr. Jane A. Weintraub for their service and presented each with a certificate and small gift. Dr. Somerman noted that three individuals will officially join the Council at its January 2018 meeting. She thanked two of them, Dr. David J. Couper and Dr. Joyce A. De Leo, for attending the present meeting as ad hoc members. Dr. Clark Stanford, who also will join the Council in January, was unable to attend.
Dr. Somerman invited NIDCR staff to introduce new personnel. Mr. John Prue, director of the Office of Information Technology (OIT), introduced Mr. Don Seymour, systems security officer, OIT. Ms. Carol Loose, chief of the Financial Management Branch (FMB), Office of Administrative Management, introduced Mr. Matthew Sierra, budget analyst, FMB. Dr. Bruce Dye, director of the Dental Clinical Research Fellowship Program, Office of Science Planning and Analysis, introduced three Dental Public Health Residents: Dr. Kathi Buss, Commander, U.S. Navy; Dr. David Schindler, Major, U.S. Air Force; and Dr. Justin Vos, Lieutenant Commander, U.S. Public Health Service. He also introduced two Dental Public Health Fellows: Ms. Aachal Devi and Dr. Chandrashekar Janakram. Dr. Janakram is the first NIDCR Fellow in the Dental Public Health and Oral Health Informatics program, which is cosponsored with the National Library of Medicine.
Dr. Somerman invited all guests to introduce themselves.
Dr. Alicia Dombroski, Executive Secretary, and Director, Division of Extramural Activities (DEA), welcomed all participants and extended a special welcome to those attending via the videocast.
II. FUTURE MEETING DATES
- January 31, 2018
- May 25, 2018
- September 13, 2018
- January 23, 2019
- May 23, 2019
- September 13, 2019
III. APPROVAL OF MINUTES FROM PREVIOUS MEETING
Dr. Alicia Dombroski invited the Council to consider and approve the minutes of the May 23, 2017, Council meeting. The Council unanimously approved the minutes.
IV. REPORT OF THE DIRECTOR, NIDCR
Dr. Somerman presented updates on NIDCR 2030, the NIH Clinical Trials policy, the Next Generation Researchers Initiative, and the NIDCR budget. She noted that the NIDCR Workshop for Dentist‒Ph.D. Trainees, convened by the NIDCR on September 13‒14, was a wonderful gathering of NIDCR-supported dentist scientists who came together to interact and exchange experiences. Dr. Lynn Mertens King, chief of the Research Training and Career Development Branch (RTCDB), reported on the workshop later during the meeting (see section VII below). Dr. Somerman’s written Director’s Report to the Council: September 2017 was provided to the Council members and is available at NIDCR website.
Dr. Somerman noted that NIDCR 2030: Envisioning the Future, Together is a separate effort from, and goes beyond, the NIDCR Strategic Plan 2014‒2019, to take risks with new initiatives. For 2030, the NIDCR imagines a world where dental, oral, and craniofacial (DOC) health and disease are understood in the context of the whole body; research informs the strategies used to promote health, prevent and treat disease, and overcome disparities in health; and all people have the opportunity to lead healthy lives. NIDCR 2030 embraces five research areas: oral health + overall health, precision health, autotherapies, oral biodevices, and workforce diversity. Dr. Somerman reported that 662 registered users accessed NIDCR’s Ideascale website to give input on the five areas and submitted 229 ideas and 271 comments. NIDCR staff have been reviewing the ideas submitted and, during lunch, met with the Council to discuss recommendations. A symposium and workshop on autotherapies has already been scheduled for January 25‒26, 2018.
NIH Clinical Trials Policy
Dr. Somerman strongly encouraged the Council members to access the NIH clinical trials website (https://grants.nih.gov/policy/clinical-trials.htm) to see NIH’s new definition of clinical trials, which reads as follows: “a research study in which one or more human participants are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effect of those interventions on health-related biomedical or behavioral outcomes.” She noted that the NIH aims to enhance stewardship by enhancing the accountability, transparency, and efficiency of clinical trials and the dissemination of results from trials. Toward this end, the NIH is providing new guidance at https://clinicaltrials.gov, which pertains to training in Good Clinical Practice; clinical trial-specific Funding Opportunity Announcements (FOAs); new review criteria, study timelines, and milestones; and expanded registration and results reporting. The guidance stipulates that a study will be considered a clinical trial if it (a) involves one or more human subjects, (b) involves one or more interventions, (c) prospectively assigns human subject(s) to intervention(s), and has a health-related biomedical or behavioral outcome. Investigators who are applying for research grant support and are unsure whether their study qualifies as a clinical trial may access https://grants.nih.gov/ct-decision/ for assistance.
Next Generation Researchers Initiative
Dr. Somerman noted that an NIH assessment of the percentage of awardees by NIH career stage (R01 equivalents), which was conducted in response to a directive based on the 21st Century Cures Act, showed that the percentage of early-stage investigators (ESIs) and early established investigators (EEIs) receiving NIH awards is decreasing. Through its Next Generation Researchers Initiative (NGRI), the NIH has set a goal to increase the number of ESIs and EEIs receiving NIH support by approximately 200 investigators each in Fiscal Year (FY) 2017, compared with FY 2016. Dr. Somerman noted that there also are NIH-wide efforts to extend paylines and provide help to ESIs and EEIs; to place greater emphasis on current NIH funding programs aimed at ESIs and EEIs [e.g., the Common Fund and NIDCR’s Sustaining Outstanding Achievement in Research (SOAR) award]; and to develop metrics to carefully monitor and evaluate outcomes of these programs. She referred the Council members to the NGRI website, https://grants.nih.gov/ngri.htm.
Dr. Somerman reported that the enacted budget for the NIDCR in FY 2017 is $425.75 million and that the President has signed a continuing resolution for FY 2018 which provides funds through December 8, 2017, at the FY 2017 enacted level.
V. The Opioid Crisis: An Update from the NIH and NIDCR
Dr. John Kusiak, Acting Deputy Director, NIDCR, and Dr. Yolanda F. Vallejo, Director, Neuroscience of Orofacial Pain and Temporomandibular Disorders Program, Integrative Biology and Infectious Diseases Branch, Division of Extramural Research (DER), presented briefs on the opioid crisis. Dr. Kusiak described the NIH response to the crisis, and Dr. Vallejo elaborated on NIH- and NIDCR-supported pain research.
Dr. Kusiak showed data revealing an approximately 10-fold increase in opioid overdose-related deaths across the United States, with some “hot spots,” between 1999 and 2015. While prescriptions for opioids fell by more than 15 percent between 2010 and 2015, overdose deaths from any opioids rose dramatically and remain 3 to 4 times higher than in the early 1990s. Provisional data from the Centers for Disease Control and Prevention show that, in 2016, there were approximately 64,000 overdose-related deaths from any drugs and approximately 50,000 from any opioids. Overdose-related deaths from cocaine and alcohol also have risen.
Dr. Kusiak said the NIH response to this crisis is part of a broader U.S. Department of Health and Human Services opioid strategy and Federal response outlined in a recent interim report by the President’s Commission on Combating Drug Addiction and the Opioid Crisis. The report recommends working with the pharmaceutical industry to develop additional medication-assisted options and new non-opioid pain relievers based on research clarifying the biology of pain.
Dr. Kusiak noted that the NIH supports cutting-edge research and participates in efforts to improve patients’ survival and pain management, care, and treatment. This past summer, under the direction of Dr. Francis Collins, Director, NIH, the NIH organized the NIH Opioid Research Initiative and convened three workshops, on Medications Development for Opioid Use Disorders and for Overdose Prevention and Reversal (held June 5); Development of Safe, Effective, Non-Addictive Pain Treatments (June 16); and Understanding the Neurobiological Mechanisms of Pain (July 7). The workshop participants identified research challenges and set forth both high-priority action items and overarching action items. The four overarching action items are to develop biomarkers for pain and treatment response, systematically evaluate target validation steps to accelerate drug development, develop a composite set of clinically relevant outcome measures to enhance clinical trials, and establish interdisciplinary collaborations to enhance knowledge of normal and altered pain circuits.
Dr. Kusiak said several NIDCR-supported grantees and a member of NIDCR’s Board of Scientific Counselors will participate in the National Academies Workshop: Advancing Therapeutic Development for Pain and Opioid Use Disorders through Public-Private Partnerships, to be held in Washington, D.C., on October 11‒12, 2017. He also noted that the NIH Council of Councils has approved a Common Fund proposal to support research on acute-to-chronic transition signatures (ACTS) for pain (now known as PACT). The effort will comprise a prospective clinical study to identify objective signatures associated with transition, as well as resilience, and an observational clinical study to identify objective signatures associated with chronic pain. It will include infrastructure development to support a data resource center, clinical coordinating center, and multi-omic analysis sites. Dr. Kusiak noted that PACT is similar to NIDCR’s Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) program and is a fast-track initiative to be funded in FY 2018.
Pain Research at the NIH and NIDCR
Dr. Vallejo reported that the NIH has a longstanding commitment to funding pain research. In FY 2016, approximately 1.5 percent (or $483 million) of NIH’s total budget supported pain research, of which $410 million addressed chronic pain and $73 million addressed acute pain. The NIDCR contributed 5.4 percent (or $25.9 million) of NIH’s total support, funding 68 projects. Of these, 45 percent were basic research, 43 percent clinical research (most on chronic pain), and 12 percent translational research. Most projects (73 percent) were research project grants (R01s, R21s, and R03s).
Dr. Vallejo said the NIDCR supports a wide spectrum of research, which includes genetic, neuroimmunologic, behavioral, psychosocial, and other studies on many diverse and complex orofacial pain conditions. In addition, the NIDCR participates in the NIH Pain Consortium with 20 other NIH institutes and offices. Established to enhance pain research and promote collaboration across the NIH, the consortium is guided by the NIH Office of Pain Policy, develops a comprehensive and forward-thinking pain research agenda for the NIH, identifies key opportunities in pain research, and increases visibility for pain research intramurally and extramurally.
Dr. Vallejo emphasized the need for research to end the opioid crisis. Safe, more effective strategies for pain management would include non-pharmacological treatments, improved biomarkers for pain, vaccines or antibodies against opioid- or pain-producing chemicals, and non-opioid analgesics. Dr. Vallejo highlighted three NIDCR-supported studies, two of which are exploring non-pharmacological treatments (high-definition transcranial direct stimulation, and web-based exercise and behavioral modification) for patients with temporomandibular disorders (TMDs), and one of which is a preclinical study to develop non-viral gene therapy for oral cancer pain and restoration of function. She also highlighted the following two projects in the NIDCR-supported National Dental Practice-Based Research Network (PBRN): a prospective, observational study of patients receiving treatment for TMD, and research on dental practitioners’ opioid-prescribing practices. In addition, Dr. Vallejo noted NIDCR-supported implementation science research which is aimed at reducing the time between de-implementing use of opioids and implementing other strategies to optimize pain management following dental extractions. She remarked on the complexity of pain management for DOC diseases and conditions and the need for a variety of treatment regimens that are sensitive and responsive to the needs of individuals suffering with chronic pain conditions while reducing reliance on and use of opioids.
VI. CONCEPT CLEARANCES
Dr. Dombroski, Director, Division of Extramural Activities (DEA), stated that the NIDCR is required to present the purpose, scope, and objectives of proposed concepts for research initiatives to the Council in a public forum for the Council’s review, discussion, and approval and for public comment. NIDCR staff presented eight concepts at the present meeting.
The National Dental Practice-Based Research Network
Dr. Dena Fischer, director of the Clinical and Practice-Based Research Program, Center for Clinical Research, presented a proposed initiative to support a third phase of the NIDCR-funded National Dental Practice-Based Research Network (PBRN), which conducts oral health research on topics of importance to dental practitioners and their patients, provides evidence useful in daily patient care, and facilitates translation of research findings into clinical practice. In 2005, NIDCR initiated support for three regional and geographically diverse PBRNs and in 2012 funded a second phase to support a national PBRN structure with six regional hubs. Key aspects of the national network include providing a unique venue for clinical research in which dental practitioners help frame research questions, and in which practitioners and their patients participate in launching studies in a timely manner, and efficiently enrolling large numbers of patients distributed widely geographically and among practice types.
Dr. Fischer said the third phase of funding, starting in 2019, will build on previous successes and incorporate refinements based on lessons learned. Examples of potential research topics could include, but are not limited to, the following: exploration of factors contributing to practitioners’ decision making, assessment of oral disease prevention or treatment outcomes through longitudinal studies, and determination of best treatment strategies for patients with oral disease. Other examples include dissemination of oral health evidence and PBRN research findings and implementation, topics of emerging public health interest, and questions of interest to dental specialty organizations.
Council discussants, Dr. Daniel W. McNeil and Ms. Tracy Hart, enthusiastically supported the concept. Dr. McNeil noted that PBRN-supported research has been reported in 130 articles in 39 different journals and that this visible productivity is important for energizing oral health clinicians to participate in research. Ms. Hart noted that the PBRNs enable patients to be involved early in research and to participate with trusted partners. They also create possibilities for developing additional patient registries.
The Council unanimously approved the concept.
FaceBase 3 – Bioinformatics and Data Management Hub
Dr. Steven B. Scholnick, director of the Developmental Biology and Genetics Program, Translational Genomics Research Branch, DER, presented a proposed concept to support the next iteration of the FaceBase consortium (FaceBase 3). Initiated in 2009 by the NIDCR, FaceBase is an incubator for cross-discipline collaborations to accelerate craniofacial research by developing, integrating, and disseminating large datasets to the broad research community. The data repository and knowledge base now has 705 individually downloadable datasets, as well as developmental atlases, an interface for viewing results from genome-wide studies, the 3D Facial Norms database, and other resources. In 2013, the NIDCR funded a second phase of FaceBase support which expires in April 2019.
The goal of FaceBase 3 is to build on the investments made in a manner that efficiently continues to improve the resource’s utility to the craniofacial research community and expands the range of data available for further analysis. The Bioinformatics and Data Management Hub would accomplish this by working directly with craniofacial researchers to incorporate their datasets into the FaceBase resource. Dr. Scholnick highlighted the need to enhance the utility of datasets for further data integration and visualization and the need for better access to and dissemination of large datasets in some areas of craniofacial biology. With FaceBase 3, the NIDCR proposes to switch from the current “hub-and-spoke” model to a “hub-only” model, so as to take advantage of the growing number of relevant datasets developed outside of FaceBase. The FaceBase 3 hub would be charged with continuing to integrate datasets while adopting or developing new tools to enhance visualization; working with NIDCR-funded and other investigators to bring in and structure their datasets; and reaching out to the wider research community through, for example, training sessions at conferences and tutorials. Dr. Scholnick noted that the concept would align with NIH goals regarding Big Data and data sharing, use of community data/metadata standards, and adherence to the FAIR (Findable, Accessible, Interoperable, and Reusable) principles for scientific data management and stewardship; etc.
Council discussants, Dr. Nisha J. D’Silva, and Dr. Sanjay Shete, enthusiastically supported the concept as being extremely important and useful. They noted that the proposed hub-only model would increase the data available exponentially and that tutorials in the use of data to generate more hypothesis-driven research would be crucially important. They encouraged linkage of the FaceBase platform to outside resources, including Big Data sites, and partnerships with industry.
The Council unanimously approved the concept.
Understanding Mechanisms of Gene-Environment Interaction in Dental, Oral, and Craniofacial Diseases and Conditions
Dr. Emily L. Harris, chief of the Translational Genomics Research Branch, DER, presented a proposed initiative to better understand biological mechanisms underpinning gene‒environment interaction in diseases and conditions central to NIDCR’s mission. She noted that while epidemiological and family studies provide evidence of this interaction (e.g., fluoride exposure and dental caries, maternal smoking and orofacial clefts), little is known about the biological mechanisms underpinning the statistical results. New technologies and information about gene regulatory networks may now be leveraged through animal models and in vitro approaches.
Particular areas of interest for the proposed initiative include use of animal models or in vitro approaches to study the interplay between candidate genes, identified through research in humans, and environmental risk factors, including in utero exposures and personal factors, as well as the development of new animal or organoid models that could provide insights into mechanisms of interaction. Dr. Harris said the concept is not intended to include human epidemiological or family studies of gene‒environment interactions.
Council discussants, Dr. Yang Chai and Dr. Daniel W. McNeil, supported the concept as being both timely and important. Dr. Chai noted that although many human and animal studies have focused on gene and environmental factors in congenital birth defects, few have combined research on known human risk factors in animal models. He encouraged development of new animal models based on mutations in human development and use of organoids. He noted that the new knowledge gained could foster understanding of health disparities across populations and development of approaches to benefit these populations. Dr. McNeil noted the importance of animal models for understanding basic biological mechanisms and gene‒environment interactions.
The Council unanimously approved the concept.
Bioinformatics/Data Science Jumpstart for Dental, Oral, and Craniofacial Diseases and Conditions
Dr. Emily Harris presented a second proposed concept, to support research on bioinformatics and data science pertaining to DOC diseases and conditions. The two goals are (i) to encourage data integration and data mining, with follow-up research as appropriate, to advance scientific questions central to NIDCR’s mission, and (ii) to attract more bioinformatics, computational biology, and data science projects and investigators to NIDCR.
Dr. Harris noted that applying mathematical and computational approaches to complex and multidimensional data (e.g., as in Big Data) can lead to deeper understanding of research data, foster new questions, and could be leveraged to further NIDCR’s mission. Two areas of interest are: (a) bioinformatics, computational biology, and data science research that will facilitate data mining, integration, or modeling, and (b) validation, mechanistic, or translational components, as appropriate to a research strategy. Dr. Harris noted while several current FOAs could support such work, they do not emphasize computational biology and could not accommodate especially large projects. The research fields and topics pursued under the concept could include, for example, genomics and other “omics,” research integrating electronic records, health services research, and 3D modeling of craniofacial structures.
Council discussants, Dr. Sanjay Shete, Dr. David J. Couper, and Dr. Anne Louise Oaklander, enthusiastically supported the concept as an exciting and timely initiative. Dr. Shete noted that it could take advantage of existing tools, bring new scientists into DOC research, and link with FaceBase datasets. Dr. Couper emphasized the need for good study designs; appropriate review; and rigor, reproducibility, and validation of the data science conducted. Dr. Oaklander noted the need to “arc” back to patients, clinicians, and other providers by ensuring that the research data developed from information they provide are made available to them.
The Council unanimously approved the concept.
Encouraging Novel Amelogenesis Models and Ex Vivo Cell Lines (ENAMEL) Development
Dr. Jason Wan, director of the Mineralized Tissue Physiology Program, Integrative Biology and Infectious Diseases Branch (IBIDB), DER, presented a proposed concept to advance understanding of enamel development. The goals are (i) to validate models for the study of amelogenesis that accurately reflect the developmental stage or physiological process they are intended to represent, and (ii) to generate any new or improved models, ensuring that they are robust and reproducible. Dr. Wan noted that amelogenesis (enamel formation) is a complex process and clinically heterogeneous, given the many genetic and environmental factors involved. Research on amelogenesis is difficult because of the limitations of current research tools. Rodent models have limited physiological relevance to humans, the availability of cell lines representing various stages of amelogenesis is limited and cell lines are not always predictable, and reproducibility across labs is problematic.
Dr. Wan said the proposed research would draw on tools now available to manipulate genes, control the microenvironment, and dissect molecular mechanisms. Four specific areas of interest are to (a) validate cells developed from pluripotent stem cells or other sources to reflect a continuum of ameloblast differentiation to maturation, (b) refine or develop new ameloblast cells lines and suitable animal models, (c) develop 3D cultures and engineering approaches to emulate the native ameloblast environment, and (d) standardize processes of development, share information, and test models for utility and reproducibility.
Council discussants, Dr. Yang Chai, Dr. Phillip B. Messersmith, and Dr. Anne C. R. Tanner, strongly supported the concept as a timely step forward for understanding enamel development. Dr. Chai encouraged emphasis on animal models to better understand enamel formation, repair, and regeneration, and he noted the need to ensure that the matrix structure in organoids and in vivo approaches represents that in enamel formation. Research on cell culture models would improve understanding of cellular interactions and repair and regeneration, and this knowledge would be useful in development of preventive measures for patient care. Dr. Messersmith highlighted the opportunity that new technologies, such as 3D printing and organoids on a chip, offer for development of novel materials. Dr. Tanner noted the concept’s potential for understanding interactions in enamel development.
The Council unanimously approved the concept.
Precision Imaging of Oral Lesions
Dr. Chiayeng Wang, director of the Oral and Salivary Gland Cancer Biology Program, IBIDB, DER, presented a proposed initiative on precision imaging of oral lesions, which was jointly developed with Dr. Gallya Gannot, Center for Clinical Research (CCR). The initiative would encourage research on precision imaging using cutting-edge technologies to enhance detection and diagnosis and, thereby, facilitate appropriate treatment and improve patients’ survival and quality of life. The long-term goal would be to promote accurate and timely diagnoses, improve treatment outcomes, and pave the way for personalized health care of orofacial tissues. Dr. Wang noted that while biopsy and histopathology remains the gold standard for diagnosis, use of this method is prone to misdiagnosis. Precision imaging that combines the science and technology of advanced biomedical imaging could fill the need for more analytical, precise, and accurate diagnosis and treatment. The spectrum of imaging technologies available includes radiomics, functional imaging, and molecular imaging and could be coupled with functional genomic techniques to add value to both biology research and clinical practice.
The initiative would focus on, but not be limited to, five areas of interest. These are (a) integration of emerging imaging technologies into clinical workflow for more effective solutions in characterizing and grading oral lesions and in determining extent and severity of disease, (b) optimization of single-cell analysis to define physiological states within heterogeneous oral lesions, (c) development of robust methods to detect lesions not detectable by conventional procedures, (d) development and optimization of intraoperative image-guided biopsy, surgery, and ablative therapies for management of oral disease, and (e) development of theranostic agents targeting biological pathways and processes to help identify early markers of oral disease and improve treatment and monitoring of therapeutic effects.
Council discussants, Dr. Nisha J. D’Silva, Dr. Yang Chai, and Dr. Shenda M. Baker, enthusiastically supported the proposed initiative because of its potential for addressing issues in diagnosing diseases and conditions with conventional procedures and providing more definitive diagnoses, thereby helping patients who are seeking care. Dr. D’Silva suggested that the proposed concept include clarification of the definition of imaging, benchmarks for assessing improvements over existing diagnostic tests, and investigation of molecular markers. Dr. Chai suggested combining precision imaging with traditional histopathological studies, to ensure accuracy of diagnosis, addressing ways to encourage clinicians to adapt new technologies, and considering how precision imaging will change clinical decision making. Dr. Baker noted that having tools to look at molecular and cellular changes in lesions before and during treatment would be very useful and could be combined with other research technologies.
In discussion, Dr. Marcelo W. B. Araujo, Vice President, Science Institute, American Dental Association (ADA), Washington, D.C., said the ADA Council on Scientific Affairs will be publishing clinical practice guidelines in October 2017 which will note that none of the current tools for diagnosing clinical diseases and conditions assures definitive diagnoses and that new, cost-effective tools need to be developed for clinical practitioners.
The Council unanimously approved the concept.
Basic and Translational Research on HIV and AIDS-Related Pathogens in the Oral Cavity
Dr. Gallya Gannot, director of the HIV/AIDS and Oral Health Research Program, CCR, DER, presented a proposed concept to support basic and translational research on HIV and AIDS-related pathogens in the oral cavity. The goal is to encourage innovative research into mechanisms of HIV transmission, persistence, pathogenesis, and comorbidities in the oral cavity. Dr. Gannot noted that the research would help address gaps in knowledge and could encourage development of improved local and systemic therapies for HIV-related oral infections and other complications in the current era of combination anti-retroviral therapy (ART).
The research supported would address, but not be limited to, the following areas of interest: (a) mechanisms of mother-to-child oral HIV transmission, (b) oral mucosa defense mechanisms in the context of HIV infection and ART, (c) mechanisms of oral HIV/AIDS prophylactic and therapeutic vaccination, (d) HIV and the oral microbiome, (e) mechanisms leading to development of caries and periodontitis in people living with HIV infection, and (f) oral comorbidities in people living with HIV infection.
Council discussants, Dr. Daniel Malamud (via telephone), Dr. Anne C. Tanner, and Dr. Yang Chai, were very supportive of the concept. Dr. Malamud noted that important issues concerning HIV transmission and the oral cavity have yet to be resolved (e.g., the mechanisms of a seemingly preventive effect of saliva and oral mucosa, the association between HIV infection and dental caries and periodontal diseases, the high transmission of HIV through breastfeeding, and interactions between HIV and the oral microbiome). He also noted the need to encourage dental professionals to utilize available tests to detect HIV infection in the oral cavity and suggested that this issue could be addressed in a separate concept. Dr. Tanner agreed with Dr. Malamud and said that while much work has been done on HIV in the oral cavity, there is more to do, particularly to understand how infants acquire HIV infection during breastfeeding. She suggested that multidisciplinary research on the roles of viruses and bacteria could be added to the concept. Dr. Chai said the broad concept presents a great opportunity to study mechanisms of HIV infection in diverse populations. He highlighted, in particular, the association of HIV and periodontal diseases and oral malignancies in people living with HIV/AIDS.
The Council unanimously approved the concept.
Biological Factors Underlying Oral and Craniofacial Health Disparities
Dr. Jane C. Atkinson, director of the Center for Clinical Research, DER, presented a proposed concept to encourage research to identify and understand biological factors (microbial, immune, genetic) contributing to disparities in the onset, progression, and persistence of DOC diseases. She noted that multiple behavioral, cultural, and socioeconomic factors, such as access to and use of health care, contribute to oral health disparities and that biological factors may play a significant role. Data from cancer registries indicate, for example, that, compared with whites, African-Americans with oral cancer have lower survival rates. Studies of other cancers demonstrating poorer outcomes for African-Americans suggest that differences in tumor characteristics may contribute to disparities in survival. Other DOC conditions exhibiting disparities in prevalence and severity include dental caries, which are more prevalent in children who are African-American, Hispanic, or American Indian and Alaska Native, and severe destructive periodontal disease that is more prevalent in racial/ethnic minority U.S. populations.
Dr. Atkinson noted that technological advances and scientific discoveries about the oral microbiome, inflammatory proteins mediating oral diseases, and genomics allow for more in-depth research into biological factors underlying health disparities. The proposed initiative includes, but is not limited to, research in the following four areas: (a) microbial and inflammatory mediators of oral diseases in different racial/ethnic groups and their contribution to differences in the prevalence and/or severity of disease; (b) biological responses to conventional therapy for DOC diseases that may explain the persistence of these diseases in different racial/ethnic minority populations; (c) biological responses to social, behavioral, cultural, and socioeconomic factors that contribute to or mediate DOC diseases; and (d) genetic/genomic risk or protective factors that might contribute to racial/ethnic differences in DOC diseases and the interplay with other factors.
Council discussants, Dr. Jane A. Weintraub and Dr. Anne C. Tanner, supported the proposed concept. Dr. Weintraub emphasized the need for multidisciplinary research teams to address the broad and complex array of and interaction among biological and social, behavioral, cultural, and socioeconomic determinants of health disparities and underlying health inequities. She noted that while the concept focuses heavily on racial/ethnic differences, the interaction between health and microbiome and the biological pathways of DOC diseases in different groups also need to be understood. Dr. Tanner encouraged research to tease out the underlying factors in DOC diseases (e.g., childhood caries) in populations with increased rates of disease.
The Council unanimously approved the concept.
VII. SPECIAL SESSION
NIDCR Research Training For Dentist Scientists
Dr. Lynn Mertens King, chief of the Research Training and Career Development Branch (RTCDB), DEA, reported on the NIDCR Workshop for predoctoral Dentist‒Ph.D. Trainees, convened by the NIDCR on September 13‒14, 2017, in Bethesda, Maryland. She noted that the workshop was both an exciting and engaging experience, and she thanked the 26 trainees and the NIDCR staff members who participated in the conference, notably Dr. Leslie Frieden, extramural training officer, RTCDB, who contributed greatly to organizing the workshop logistics and activities. A workshop booklet containing a message from the Director, NIDCR, the 2-day agenda, and each trainee’s personal statement and research abstract was distributed to the Council members. The Council applauded this NIDCR effort.
Dr. King described the goals of the workshop, which included an opportunity to provide a networking experience for predoctoral dual-degree trainees participating in the NIDCR Dentist Scientist Training Program (DSTP). The workshop participants are supported by NIDCR Ruth L. Kirschstein National Research Service Awards (NRSA). The NIDCR supports D.D.S./D.M.D. and Ph.D. dual doctoral degree training under the Ruth L. Kirschstein NRSA institutional T32/T90 research training grants and individual F30 fellowship awards. U.S. citizens, non-citizen nationals, and permanent residents are eligible to receive NRSA support. The NRSA dual doctoral degree programs provide up to 6 years of support (stipend, tuition, and fees) for integrated clinical training and Ph.D. research training. Trainees are required to devote full-time effort (40 hours per week) to the dual degree program activities The NIDCR currently supports institutional training grants at 17 U.S. universities and research institutions. Of these awards, 12 of the training grants support dual D.D.S./D.M.D.-Ph.D. degree programs. Each dual degree program is designed for students to complete the D.D.S./D.M.D. and Ph.D. degrees over a 7- to 8- year time frame; however, the phasing and integration of the clinical and research training program are uniquely designed to align with each university/dental school’s programmatic priorities and their institution’s clinical and graduate school requirements.
Dr. King noted that the NIDCR continues to support a broad array of research training and career development opportunities across its extramural and intramural programs and at all career levels, from high school to established investigator. In addition, the NIDCR funds research supplements to promote diversity and re-entry into the biomedical workforce. These different funding opportunities provide some flexibility in how dentists can pursue a research career pathway, including optional Ph.D. research training, and fellowship, career development, or career transition awards to achieve an independent research career and research support. NIDCR staff work individually with students and dentist postdocs to help navigate the options and tailor a pathway based on their previous experience and future research goals. Over the past 16 years, from 2001 to 2017, the NIDCR has supported 166 dual-degree D.D.S./D.MD‒Ph.D. trainees in research areas across the NIDCR extramural research portfolio. Dr. King encouraged individuals interested in NIDCR-supported research training and career development to contact NIDCR staff for guidance and to access the information available at Careers and Training
VIII. NIDCR Trainee Presentations
Three individuals who participated in the September 13-14 NIDCR Workshop for Dentist‒Ph.D. trainees gave presentations to Council. Each trainee thanked NIDCR for its research training support, described his or her research and DSTP experience, and commented on opportunities and challenges for DSTP trainees. They all warmly acknowledged and thanked their mentors and research collaborators. All three are supported by NIDCR Individual Predoctoral D.D.S./D.M.D.-Ph.D. Fellowship (F30) awards. Their plans on graduating from the DSTP include pursuing a research-focused career trajectory, gaining dental specialty and postdoctoral training, and ultimately acquiring a faculty position in a research-intensive institution.
Mr. Christopher R. Donnelly is a DSTP trainee in the Department of Biologic and Materials Sciences, University of Michigan School of Dentistry. His research focus is on understanding the function of GFL-rat signaling in the development of the peripheral sensory nervous system. Mr. Donnelly said his passion for research took shape during his undergraduate years as a pre-med student and was leading him to pursue an M.D.-Ph.D. when he decided to shift to dentistry because of its orientation to patients and communities. He did not learn about the DSTP until he interviewed for dental school. In choosing a training program, he decided on the University of Michigan because of its emphasis on the Ph.D. component; its strong research environment, particularly in neuroscience research; and the opportunity to pursue a personal interest in sensory neurobiology. At Michigan, he has been able to pursue a variety of projects related to signaling mechanisms underlying the development of peripheral neural circuits and spanning research techniques from molecular studies to animal models. The Michigan program consists of 3 years of Ph.D. research training, followed by the D.D.S. curriculum. Mr. Donnelly is in his 7th year of the dual-degree program and the 2nd year of dental school.
Commenting on opportunities for DSTP trainees, Mr. Donnelly highlighted the real potential to induce meaningful change by addressing important issues in dentistry; the number of institutes supportive of orofacial neuroscience; the small, but highly supportive community of scientists; and the ability to benefit from a “dental school niche” and an increasing demand for dentist-scientists, compared with Ph.D. and M.D.-Ph.D. scientists. He mentioned that neurobiologists often overlook craniofacial and oral sensory biology. Mr. Donnelly noted the following challenges facing DSTP trainees: deciding on whether to be a researcher or clinician, finding out about the DSTP, logistical challenges in finding time for research in varying dental curricula, and lack of a mechanism of support for DSTP graduates interested in combining residency training and postdoctoral research. He emphasized needs to “get the word out” about the DSTP, provide more flexibility and improve time management in the D.D.S. training component, and help DSTP graduates transition to residency programs or research.
Ms. Marybeth Francis is in the DSTP program at the University of Illinois at Chicago (UIC) College of Dentistry. Her research focuses on pathways of pathogenesis in patients with diabetes and periodontitis that lead to activation of the pro-inflammatory transcription factor NF-kB. Ms. Francis said she was initially interested in a pre-med or pre-dental program and upon graduation with a B.S., took a position with Covance while also pursuing an M.A. in biotechnology at the University of Wisconsin. She then decided to go to dental school at UIC, where she learned about the DSTP during her application interview. She is in year 6‒7 of the DSTP at UIC, which is structured as follows: year 1 Ph.D. training, year 2 dental school, years 3 and 4 Ph.D. training, and years 5‒7 dental school.
Ms. Francis presented a brief overview of her research. Addressing the opportunities for DSTP and D.M.D.-Ph.D. trainees, she highlighted the value of clinical experience and patient contact for identifying research problems and developing research projects. She agreed with Mr. Donnelly on the challenges facing DSTP trainees, noting that transition between the Ph.D. and D.D.S. or D.M.D. curricula is very challenging. She also noted that undergoing two demanding programs and relating to new classmates who may not be in the 7-year dual-degree program are additional challenges and that trainees have to keep in mind their long-term goals to become leaders in dental research.
Mr. Shaun R. Abrams is a DSTP trainee in the Oral and Craniofacial Sciences Graduate Program, University of California, San Francisco (UCSF) School of Dentistry. His research focuses on the role of the primary cilia transition zone complex in craniofacial ciliopathies. He said he had no research experience in his undergraduate years at a small historically black college and was set on pursuing dentistry, following his mother who is a dentist. Encouraged by a mentor to try research before going to dental school, he applied for and was accepted into the Postbaccalaureate Research Education Program at The Johns Hopkins University School of Medicine, a research-intensive training program for underrepresented groups. He noted that this experience “lit the spark” for his interest in research and led to his first publication before entering graduate school. However, it was not until he met Dr. Deborah Philp, Office of Education, Division of Intramural Research (DIR), NIDCR, at a conference that he learned about dental research. He then applied for and received a second postbaccalaureate award, the NIH/NIDCR Technical Intramural Research Training Award, which provided 3 years of research training support in the NIDCR Intramural Program. Mr. Abrams noted that it was this experience that cemented his desire to pursue a combined D.D.S.-Ph.D. degree. He subsequently entered the DSTP at UCSF, which consists of 4 years of Ph.D. training, followed by 4 years of dental school. He is in his 6th year of the program and the 2nd year of dental school. He noted that in the UCSF program, trainees can choose their thesis advisor from across the university and select three laboratories through which to rotate.
Noting that he has a broad interest in craniofacial development, Mr. Abrams elaborated on his research on ciliopathies, a class of disorders affecting the entire body and caused by cilia. Craniofacial ciliopathies include midface dysplasia, his particular focus, as well as jaw disorders, tongue abnormalities, palate defects, and abnormal dentition. Mr. Abrams highlighted the following three specific challenges he has encountered in the DSTP: choosing a Ph.D. mentor who did not have expertise in craniofacial biology, necessitating him to reach outside the laboratory for a secondary mentor, and did not previously know about the DSTP; maintaining research productivity and training during the D.D.S. phase of the program; and lack of communication and integration between D.D.S. and graduate program faculty and administration.
Dr. Matthew P. Hoffman, deputy scientific director of the DIR, invited the trainees to comment on several issues. Mr. Donnelly noted that his future efforts to combine research with a residency program could be facilitated by getting involved with the professional community of researchers in his field and placing himself in a university setting where such accommodations are possible. He suggested that creating slots in institutional training grants to support a combined research‒residency program might be helpful. Mr. Abrams commented on the issue of maintaining one’s research interests while in dental school. He said he is able to “get back” into the lab during school breaks and has forged relationships with lab personnel to help him continue to move his research forward. Ms. Francis noted that her previous experience working in industry with biotechnology has been helpful and possibly could be expanded through the NIDCR’s Small Business Innovation Research award program after she graduates from the DSTP program. The trainees agreed that the NIDCR workshop was very important in enabling them to network with other DSTP trainees, and they suggested that similar networking workshops could be held in conjunction with annual meetings of the American Association for Dental Research.
Dr. Somerman thanked everyone who participated in DSTP workshop. She noted that it was an incredible 2 days and a pleasure to host the trainees who displayed such commitment and energized the NIDCR.
IX. ADJOURNMENT OF OPEN SESSION
Dr. Dombroski adjourned the open session of the Council meeting at 12:15 p.m.
This portion of the meeting was closed to the public in accordance with the determination that it was concerned with matters exempt from mandatory disclosure under Sections 552b(c)(4) and 552b(c)(6), Title 5, U.S. Code and Section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. Appendix 2).
X. REVIEW OF APPLICATIONS
The Council considered 318 applications requesting $78,413,111 in total costs. The Council recommended 187 applications for a total cost of $46,497,471 (see Attachment II).
The meeting was adjourned at 1:52 p.m. on September 15, 2017.
I hereby certify that the foregoing minutes are accurate and complete.
Dr. Martha J. Somerman, Chairperson
Dr. Alicia Dombroski, Executive Secretary
National Advisory Dental and Craniofacial Research Council