Date: May 20, 2015
Place: Conference Room 10
National Institutes of Health
The 209th meeting of the National Advisory Dental and Craniofacial Research Council (NADCRC) was convened on May 20, 2015, at 9:00 a.m., in Building 31, Conference Room 10, National Institutes of Health (NIH), Bethesda, Maryland. The meeting was open to the public from 9:00 a.m. to 12:38 p.m.; it was followed by the closed session for Council business and consideration of grant applications from 1:30 p.m. until adjournment at 1:57 p.m. Dr. Martha Somerman presided as Chair.
Dr. Hector G. Balcazar
Dr. Yang Chai
Dr. Teresa Ann Dolan
Dr. Yvonne L. Kapila
Dr. Jane B. Lian
Dr. Mary L. Marazita
Dr. Anne C. R. Tanner
Dr. Jane A. Weintraub
Dr. Benjamin Alexander White, Jr.
Dr. J. Leslie Winston
Ex Officio Members
Dr. Patricia E. Arola
Ad Hoc Members
Dr. Richard Peters Darveau
Ms. Tracy Hart
Members of the Public
Dr. Brad A. Amendt, Director, Craniofacial Anomalies Research Center, and Professor of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City
Mr. Benjamin Anders, 2015 ADEA/Sunstar Americas, Inc./Jack Bresch Student Legislative Intern, American Dental Education Association (ADEA), Washington, D.C., and dental student, University of North Carolina at Chapel Hill School of Dentistry
Dr. Azeez Butali, Assistant Professor, Department of Oral Pathology, Radiology, and Medicine and Dows Research Institute, College of Dentistry, University of Iowa, Iowa City
Mr. Ryne Chua, Program Associate, Policy Center - Advocacy and Government Relations, ADEA, Washington, D.C.
Dr. Yvonne Knight, Senior Vice President for Advocacy and Government Relations, ADEA, Washington, D.C.
Dr. Sarah Knox, Assistant Professor, Department of Cell and Tissue Biology, School of Dentistry, University of California, San Francisco
Mr. B. Timothy Leeth, Senior Director for Federal Relations, Policy Center- Advocacy and Government Relations, ADEA, Washington, D.C.
Dr. Daniel Meyer, Senior Vice President of Professional Affairs and Chief Science Officer,
American Dental Association, Chicago, IL
Ms. Carolyn Mullen, Director of Government Affairs, American Association for Dental Research (AADR), Alexandria, VA
Dr. Gregory Olson, ADEA/Sunstar Americas, Inc./Harry W. Bruce, Jr. Legislative Fellow,
Policy Center - Advocacy and Government Relations, ADEA, Washington, D.C., and Assistant Professor, Lorna Linda University School of Dentistry, California
Federal Employees Present
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. Margo Adesanya, OD, Office of Science Policy and Analysis (OSPA)
Dr. Karina Boehm, OD, Office of Communications and Health Education (OCHE)
Dr. Preethi Chander, DER, Integrative Biology and Infectious Diseases Branch (IBIDB)
Ms. Patty Chestnut, Office of Administrative Management (OAM)
Dr. Dave Clark, DER, Behavioral and Social Sciences Research Branch (BSSRB)
Dr. Kevin Crist, DEA, Grants Management Branch (GMB)
Ms. Mary A. Cutting, DER, Center for Clinical Research (CCR)
Mr. Bret Dean, OAM, Financial Management Branch (FMB)
Dr. Donald DeNucci, DER, CCR
Dr. James L. Drummond, DER, IBIDB
Dr. Olga Epifano, DEA
Dr. Dena Fischer, DER, CCR
Dr. Leslie Frieden, DEA, Research Training and Career Development Branch (RTCDB)
Dr. Crina Frincu, DEA, Scientific Review Branch (SRB)
Mr. Joel Guzman, DER
Dr. Emily Harris, DER, Translational Genomics. Research Branch (TGRB)
Ms. April Harrison, DEA, GMB
Ms. Jeannine Helm, DER
Dr. Victor Henriquez, DEA, SRB
Mr. Gabriel Hidalgo, DEA, GMB
Dr. Matthew Hoffman, DIR, LCDB, MMS
Dr. Laura Hsu, DER, CCR
Dr. Wendy Knosp, OD, OSPA
Ms. Susan Lowenthal, DEA, GMB
Dr. R. Dwayne Lunsford, DER, IBIDB
Ms. Jayne Lura-Brown, DER
Dr. Amanda Melillo, DER, IBIDB
Dr. Dawn Morales, DER, BSSRB
Dr. Ruth Nowjack-Raymer, DER, CCR
Ms. Lisa Peng, OD, Office of Information Technology (OIT)
Mrs. Debbie Pettitt, DEA, GMB
Ms. Ann Poritzky, Web Analytics Lead, OD, OCHE
Mr. Fernando Portillo Ventura, OD, OIT
Mr. John Prue, OD, OIT
Dr. Melissa Riddle, DER, BSSRB
Ms. Delores Robinson, DEA
Dr. Isaac Rodriguez-Chavez, DER, IBIDB
Ms. Diana Rutberg, DEA, GMB
Dr. Steven Scholnick, DER, TGRB
Dr. Yasaman Shirazi, DEA, SRB
Dr. Katie Stein, DER, TGRB
Ms. Kathleen Stephan, OD, Associate Director for Management, OAM
Mr. Larry Sutton, OD, OAM
Ms. Loan Ta, OD, OSPA
Dr. Sundaresan Venkatachalam, DER, IBIDB
Dr. Jason Wan, DER, IBIDB
Ms. Delores Wells, OSPA
Dr. Lois K. Cohen, Consultant
Other Federal Employees
Dr. Eric Green, Director, National Human Genome Research Institute, NIH
Dr. Gary Schumacher, ADA Foundation Volpe Research Center, National Institute of Standards and Technology, Department of Commerce, Gaithersburg, MD
I. WELCOME AND INTRODUCTIONS
Dr. Martha Somerman, Director, NIDCR, called the 209th meeting of the Council to order. She welcomed Council members, guests, and attendees participating via the NIH videocast. Dr. Somerman invited guests at the meeting to introduce themselves and then invited NIDCR staff to introduce new personnel.
Dr. Lillian Shum, Director, Division of Extramural Research (DER), introduced two staff members who have assumed new responsibilities, as follows: Dr. Amanda Melillo has been appointed director of the Salivary Biology and Immunology Program within DER's Integrative Biology and Infectious Diseases Branch (IBIDB), and Ms. Jeannine Helm has been promoted to health specialist at the DER division level. Dr. Shum also introduced Dr. Preethi Chander, who recently joined IBIDB as a health specialist.
Dr. Yasaman Shirazi, chief of the Scientific Review Branch (SRB), Division of Extramural Activities (DEA), introduced Dr. Crina Frincu, who has joined SRB as a scientific review officer. Ms. Diana Rutberg, DEA's chief grants management officer, welcomed Mr. Gabriel Hidalgo back to the NIDCR as lead grants specialist in the Grants Management Branch. Dr. Ruth NowjackRaymer, director of the Health Disparities Research Program, Center for Clinical Research' (CCR), introduced Dr. Laura Hsu, who has joined CCR as a health specialist. Dr. Emily Harris, chief of DER's Translational Genomics Research Branch (TGRB), introduced Dr. Kathryn Stein, who has joined TGRB as a health specialist. Dr. Melissa Riddle, chief of DER's Behavioral and Social Sciences Research Branch (BSSRB), introduced Dr. Dawn Morales, who has joined BSSRB as a health specialist. And, Dr. Margo Adesanya, acting director of the NIDCR's Office of Science Policy and Analysis (OSPA), introduced Ms. Loan Ta, who has joined OSPA as a program analyst.
Dr. Somerman applauded all the new staff members and noted that they came from within and outside the NIH as great candidates to fill openings at the NIDCR.
II. FUTURE MEETING DATES
September 18, 2015
January 22, 2016
September 20, 2016
January 24, 2017
May 23, 2017
September 15, 2017
III. APPROVAL OF MINUTES FROM PREVIOUS MEETING
Dr. Alicia Dombroski, Executive Secretary, NADCRC, also welcomed the Council members, guests, and virtual participants. She invited the Council to consider and approve the minutes of the January 27, 2015, Council meeting. The Council unanimously approved the minutes.
IV. REPORT OF THE DIRECTOR, NIDCR
Dr. Somerman invited Council's questions on the written Director's Report to Council: May 2015, which was provided to the Council members and is available on the NIDCR website. Later, following a presentation on the Precision Medicine Initiative at the NIH, Dr. Somerman reported on NIDCR activities to advance precision oral health care through research (see section VII below).
V. SPECIAL SESSION ON THE NIDCR PATHWAY TO INDEPENDENCE (K99/ROO) PROGRAMS
Dr. Leslie Frieden, Extramural Training Officer, Research Training and Career Development Branch, DEA, presented an overview of the NIDCR Pathway to Independence Awards (K99/ROO) programs. Following her presentation, she introduced two invited speakers who shared their experiences in utilizing these programs to gain research independence.
Dr. Frieden described the NIDCR's use of the K99/ROO award mechanism, the characteristics of K99/ROO applicants and awardees, and the outcomes thus far. She noted that the NIDCR supports a broad range of research training programs, which include individual and institutional awards, intramural and extramural training, career opportunities for high school students up to established investigators, and research supplements to promote diversity and career re-entry.
Dr. Frieden specified that the NIDCR supports two distinct K99/ROO programs: the parent NIH Pathway to Independence Award, for which the NIDCR initiated support in Fiscal Year (FY) 2007, and the NIDCR Dentist Scientist Pathway to Independence Award, which began in FY 2010. The goal of both is to enable postdoctoral trainees to transition to tenure-track faculty positions at earlier stages in their careers. The K99/ROO is a 5-year award that supports mentored research training in the K99 phase (1-2 years) and independent research in the ROO phase (3-4 years). The NIDCR Dentist Scientist Pathway award offers an optional 2-year extension of the ROO phase to accommodate part-time dental specialty training, for an award total of 7 years. For both programs, eligible candidates may be U.S. citizens, permanent residents, or non-citizens; must have a doctoral degree, which for the NIDCR Dentist Scientist Pathway award would be a dual D.D.S.-D.M.D. and Ph.D.; be in a mentored research position; have fewer than 4 years of postdoctoral research; and be sponsored by a domestic institution. For awardees, 75 percent of their effort is protected research time, and 25 percent may be dedicated to non-research activities, including clinical practice, clinical training, teaching, and administrative responsibilities. For the K99 phase, each awardee receives $75,000 as salary and $25,000 for research; for the ROO phase, each receives $249,000 in total costs.
Dr. Frieden highlighted possible career pathways by which citizens and non-citizens could utilize NIH mechanisms of support to obtain NIH postdoctoral research training, proceed to a K99/ROO, and eventually attain independent research and career development support. Summarizing data on the characteristics of K99/ROO applicants and awardees, Dr. Frieden noted the following points. (a) The number ofNIDCR applications for K99 awards is small and fluctuates (in FY 2014, there were 14 applications for the NIH parent award and 6 for the NIDCR Dentist Scientist award); (b) the overall success rates are higher than the average for the NIH (50 percent and 33 percent respectively in FY 2014, compared with 22 percent for the NIH); (c) the mix of citizen and non-citizen applicants and awardees is approximately equal (of the 115 applicants and 51 awardees for the NIDCR K99/ROO in FY 2010-FY 2014, 59 percent were citizens and 41 percent were non-citizens); (d) postdoctoral and predoctoral T32 awards are the most frequent prior NIH training support, excluding non-citizens; and (e) the NIDCR is the largest source of prior training support for the awardees.
Dr. Frieden noted specifically that (f) introduction of the NIDCR Dentist Scientist Pathway K99/ROO in FY 2010 increased the number of D.D.S.-Ph.D. applicants; (g) dual-degree dentist scientists comprised a higher number of K99/ROO applicants and awardees in FY 2010-FY 2014 than in FY 2007-FY 2009 (24 and 10, respectively, versus 11 and 3) and had a higher success rate (44 percent versus 27 percent); and (h) the 7-year project period was used as an option (requested by 32 percent and 40 percent of applicants and awardees, respectively). Dr. Frieden mentioned that the NIH has few K99/ROO physician-scientist (M.D.-Ph.D.) applicants (e.g., 34, compared with 700 Ph.D. applicants, in FY 2012).
Dr. Frieden highlighted outcomes of the two NIDCR K99/ROO programs. In the NIH parent K99/ROO program, the NIDCR made 41 awards beginning in FY 2007 through FY 2014. Of these, 13 are active K99s, 25 transitioned to ROOs, and 3 did not transition. Of the 25 awardees in the ROO phase, 18 transitioned to a new institution and 7 transitioned within their training institution. The median time spent in the K99 phase prior to transitioning to the ROO phase was 12 months (with a range of 6-38 months). In the NIDCR Dentist Scientist K99/ROO program, the NIDCR made 10 awards beginning in FY 2010 through FY 2014. Of these, 4 are active K99s and 6 transitioned to ROOs. Of the 6, 2 received 5-year project periods, to accommodate part-time clinical specialty training, and 4 requested 3-year project periods; 5 individuals transitioned in place, while 1 transitioned to a new institution. The median time in the K99 phase prior to transitioning to the ROO phase was 24.5 months (with a range of 24-27 months).
Dr. Frieden reported that 234 publications are attributed to NIDCR K99/ROO awardees in FY 2007-FY 2014. She noted that the award facilitated achievement of tenure-track research faculty positions: That is, 33 (or 65 percent) of awardees have research-intensive independent positions, 16 (or 31 percent) have research-intensive dependent positions, and 8 are in industry or research-related positions. Of the 25 individuals who transitioned to the ROO phase in the NIH parent K99/ROO program, 21 have applied for an NIH research project grant (RPG) and 12 have received an RPG, while 19 have applied for an independent investigator-initiated RPG (R01), and 9 have received an R01.
In closing, Dr. Frieden said that continued evaluation and tracking of the two K99/ROO programs are necessary to establish comprehensive outcomes. She noted that in FY 2012, based on the success of the NIH K99/ROO program, the NIH Advisory Committee to the Director's Biomedical Workforce Working Group recommended that the NIH increase the number of K99/ROO awards supported. And in July 2014, in recognition of the success ofthe NIDCR Dentist Scientist Pathway K99/ROO, the NIH Advisory Committee to the Director's NIH Physician-Scientist Workforce Working Group recommended that the NIH develop a K99/ROO tailored to physician scientists.
In response to questions, Dr. Frieden said that dental schools hired 100 percent of the ROO awardees in the NIDCR Dentist Scientist K99/ROO program and approximately 60 percent of the ROO awardees in the NIH parent K99/ROO program. The Council commented on the ratio of citizens and non-citizens participating in the K99/ROO programs, the trend for trainees to remain at their institutions of training, and the need for flexibility by institutions to accommodate the 25 percent of time required for specialty training and clinical duties. The Council encouraged the NIDCR to continue its outreach to inform dental school deans, department chairs, and research groups about the importance of the K99/ROO programs for developing the dental scientists who are very much needed in dental schools.
Genetics and Genomics of Cleft Lip and Palate in Sub-Saharan African Populations
Dr. Azeez Butali, Assistant Professor, Department of Oral Pathology, Radiology, and Medicine, and Dows Research Institute, College of Dentistry, University of Iowa, Iowa City, described his career progression, from trainee to independence, and his current work on genetics and genomics of clefting. Dr. Butali said that he received a degree in dentistry in 2001 from the University of Lagos, Nigeria, and that while serving as a dental intern, first experienced cleft lip and/or palate (CL/P) in Sub-Saharan African children. After several years of national service and private clinical practice in periodontology, he entered a Ph.D. program in 2006 at the World Health Organization (WHO) Collaborating Center, University of Dundee, and received a Ph.D. in 2010, with a focus on dental facial deformities.
Dr. Butali related the progress he has made toward accomplishing his fourfold plan to: (i) work closely with CL/P teams across Africa, (ii) set up craniofacial birth defect registries in Africa, (iii) investigate the causes of orofacial clefts in different groups, and (iv) plan strategies for prevention. He said that he has established close working relationships with government and non-government organizations across Africa, has been able thus far to set up hospital registries of birth defects, is developing the infrastructure to investigate causes of orofacial clefts, and is collaborating on strategies for prevention. For the future, his plan is to influence government policies to make craniofacial abnormalities a health priority in Africa. Dr. Butali noted that through publications and conferences, such as the Pan African Association for Cleft Lip and Palate Meeting in 2006, and through groups, such as the Nigerian Craniofacial Anomalies Network of 10 collaborating centers, he has been able to enlist physicians and scientists across Africa to address CL/P and promote registries and research.
Dr. Butali stated that his own research to understand the molecular genetics of individual CL/P began in 2008 while he was a visiting scholar in Dr. Jeffrey Murray's laboratory at the University of Iowa. On receiving a postdoctoral research fellowship there in 2009, he focused specifically on two genes implicated in CL/P in Asian populations, PAX7 and VAX7. On Dr. Murray's suggestion, he sought and received a K99/ROO award to provide a solid platform for becoming a successful independent researcher. Dr. Butali noted that the K99/ROO award enabled him (a) to enhance his skills in scientific communication and writing (which resulted in his publishing 10 articles and receiving four research grants, including two from the NIDCR) and (b) to broaden his understanding of the responsible conduct of research (which led to his receiving approval from institutional review boards for four applications and being named a faculty facilitator at the University of Iowa).
Dr. Butali said that the K99/ROO experience and follow-up support has made it possible to expand multidisciplinary collaborations on CL/P in Africa (e.g., through the African Craniofacial Anomalies Network); to extend research collaborations to identify sub-clinical cleft phenotypes
in African populations; and to deepen his understanding of the genetics of complex diseases across different populations. He noted that the genome-wide association studies (GWAS) which have identified 16 loci associated with clefts are mainly representative of European and Asian populations. Dr. Butali emphasized the need to identify new risk loci specific to African populations and to thereby gain additional insights into the biology of non-syndromic clefts. He noted that he is currently funded to conduct the first GWAS of clefts in African populations and to participate in multiethnic CL/P studies. In addition, he is involved in next-generation sequencing studies of the exome to identify and understand variants in gene expression. This research will make possible genetic counseling for at-risk families, primary prevention, and improved treatment to gain better outcomes.
Dr. Butali noted also that with the K99/ROO, he benefited from having a strong and successful mentor and, in turn, has successfully mentored undergraduate and dental students from the United States and overseas and has had the opportunity to advise and mentor postdoctoral fellows, associates, and young investigators, which include one K99/ROO awardee and three current K99/ROO applicants. He said his vision for the future is to continue to play a leading role in craniofacial research globally and to participate actively in the International Association for Dental Research (IADR) Global Oral Health Inequalities Research Network (GOHIRN), the International Cleft Lip and Palate Association, and other global efforts to prevent cleft lip and palate.
Salivary Glands and the Nervous System: A Story of Development and Regeneration
Dr. Sarah Knox, Assistant Professor, Department of Cell and Tissue Biology, School of Dentistry, University of California, San Francisco (UCSF), described her transition from working in the NIDCR intramural program to "flying solo" in the extramural research community via use of the K99/ROO mechanism. She emphasized that the K99/ROO award helped her move from intramural research to extramural research and to pursue her passion and enthusiasm for studying development and regeneration of salivary glands and the associated nervous system.
Initially, as an investigator in the intramural NIDCR Laboratory of Cell and Developmental Biology, led by Dr. Matthew Hoffman, Dr. Knox focused on neuronal-epithelial interactions regulating salivary gland development and regeneration in mice. In this research, she observed that the parasympathetic ganglion and salivary gland epithelium develop in parallel and in 2006, submitted a K99/ROO application to investigate the importance of nerves in salivary gland development and, in particular, the role of secretory vesicles containing neurotransmitters (e.g., acetylcholine). Subsequently, with K99/ROO support and in collaboration with Dr. Hoffman and others, she determined that neuronal signals maintain K5+ progenitor cells, that neurturin produced by the end bud epithelium promotes the outgrowth of axons and the function and survival of neurons, and that treatment with neurturin after irradiation increases glandular growth and restores parasympathetic function. She and colleagues further found that patients with head and neck cancer who have been treated with irradiation exhibit a decreased number of acini cells, neurturin expression, and parasympathetic innervation. Dr. Knox noted that this finding, which suggests that neurturin could be helpful in restoring salivary gland function in such patients, was crucial to her later R01 application.
Dr. Knox noted that the K99/ROO award facilitated her research development, skill in creating and writing research grant applications (for R21 and R01 awards), and mentoring of research students. She remarked that the award enabled her to attract the attention of eight research universities, from which she selected the UCSF for pursuing the ROO phase. There, she received guidance and direction under the ROO to enable her to establish her own research laboratory and to apply for an R01. Dr. Knox said that she also benefited by being a member of a diverse cohort of K99/ROO recipients.
Dr. Knox noted that her current research builds on the foundation made possible by the K99/ROO award. She continues to focus on how nerves guide the development and regeneration of organs, and in her laboratory, she and colleagues are working on mouse genetics, adult regeneration, human fetal and adult tissues, aging and senescence, and Sjögren's syndrome. In continued studies of neurturin, they have shown that blocking neurturin reduces innervations and disrupts duct formation; that neurturin up-regulates vasoactive intestinal peptide (VIP) by nerves; and that neuronal VIP regulates multiple steps during duct development. They also are screening for genes that are changed in the absence of nerves and are studying the importance of SOX2 in human tissue and organ development. In addition to these studies of how nerves regulate progenitor cell maintenance and morphogenic processes, Dr. Knox and colleagues are newly focusing on understanding the contribution of progenitor cells (e.g., SOX2) and neuronal signals to regeneration of adult organs during homeostasis and after injury.
Dr. Knox noted that her current work on neuronal control of salivary progenitors during development and regeneration is supported by an RO1. She said that her research continues to benefit from daily interactions in multiple clinics at UCSF and monthly meetings with clinicians.
The Council commended Dr. Butali and Dr. Knox on their presentations and research and asked them to comment on how the K99/ROO program could be improved. Dr. Butali and Dr. Knox both applauded the K99 phase for providing positive, immense, and proactive support. With respect to the ROO phase, Dr. Butali suggested that the NIDCR might help assure that institutional program directors honor the 25 percent specialty/clinical training time allotted for dentist scientist awardees, and Dr. Knox noted that more mentoring and networking support is needed to help awardees
identify and decide "where to go next" in their transition to other institutions.
VI. PRECISION MEDICINE INITIATIVE
Dr. Eric Green, Director, National Human Genome Research Institute (NHGRI), NIH, described the background, vision, and planning for the U.S. Precision Medicine Initiative, which President Obama formally launched on January 30, 2015. He noted that the concept of precision medicine (i.e., medical care based on individual genetic, environment, and lifestyle characteristics) reflects the President's longstanding interest in genomics and builds on the National Research Council's 2011 report, Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease (The National Academies Press).
Dr. Green stated that the President began to explore the possibility of a broad genomics initiative in spring 2014 in discussion with Dr. Francis Collins, Director, NIH, Dr. Eric Lander, Co-Chair, President's Council of Advisors on Science and Technology (PCAST), and White House staff. In early October, these leaders presented an informal plan and budget for precision medicine to the President, and on January 20, the President announced the initiative in his State of the Union address to Congress, receiving applause from both parties. Dr. Green noted that on January 28, when Secretary of Health and Human Services (HHS) Sylvia Mathews Burwell came to the NIH for a "town hall" meeting, she stated that precision medicine is a Presidential priority. He emphasized that the President views the initiative as part of his legacy and wants it to be rigorous, multidisciplinary, and audacious.
Addressing the vision for the initiative, Dr. Green referred the Council to a perspective article entitled "A New Initiative on Precision Medicine," co-authored by Dr. Collins and Dr. Harold Varmus, as former director of the National Cancer Institute (NCI), and published online by the New England Journal of Medicine (NEJM) on January 30, 2015 (www.NEJM.org). He noted that in the near term, cancer, a ready-to-go opportunity and model for precision medicine, is the "leading edge" of the initiative, and in the longer term, the model will be expanded to other diseases. The aim is to create a national research cohort of more than 1 million volunteer individuals who will contribute to a knowledge base for precision medicine. Dr. Green noted that barriers to clinical participation are being addressed and that Federal rules and regulatory frameworks will be updated with oversight by the U.S. Food and Drug Administration (FDA). He referred the Council to a perspective article by Dr. Lander addressing the changes needed in
regulatory frameworks (see "Cutting the Gordian Helix—Regulating Genomic Testing in the Era of Precision Medicine," published online by the NEJM on February 17, 2015, www.NEJM.org).
Dr. Green reported that the proposed budget for the Precision Medicine Initiative begins with $215 million in FY 2016. This first-year appropriation will be allocated among the NIH ($200 million), the FDA ($10 million), and the Office of the National Coordinator for Health Information Technology ($5 million). And, the NCI will administer the cancer component for the NIH. Dr. Green said that while no formal plan is in place yet, many planning activities are underway. A first, major step will be recruitment of the national research cohort of volunteer participants, from existing and newly recruited cohorts, who will share their genomics data, lifestyle characteristics, biological samples, and electronic health records (ERRs). Dr. Green noted that the initiative will forge a new model for doing science—one that is founded on research-client partnerships, open and responsive data sharing, and strong privacy protections. By using EHR data for research, the entire health care system will be converted into a "learning system."
Dr. Green commented that "everything old is new again," for in 2004, Dr. Collins had envisaged development of a national cohort for studying gene-environment interactions (see the insight commentary entitled "The Case for a U.S. Prospective Cohort Study of Genes and Environment," published in Nature 429:475-477, 27 May 2004). He noted that although this idea was ahead of its time then, the momentum for it has accelerated with advances in genomics (e.g., dramatically decreased costs of gene sequencing), expanded use of EHRs (now in 95 percent of health care settings), new technological opportunities (e.g., wearable sensors, smartphones), the transformation of biomedical research by data science, and the expressed interest of Americans in participating and partnering in research (e.g., citizen science movements).
Dr. Green said that the NIH is currently exploring ways to develop the national cohort and has set forth an aggressive timeline of next steps, which move forward from the NIH kickoff event, the Public Workshop on Building a Precision Medicine Research Cohort, which was held at the NIH on February 11-12, 2015, and was widely viewed on videocast. He noted that additional meetings and workshops, which will be webcast and video-archived, will be held this summer and that the Advisory Committee to the Director's Working Group on the Precision Medicine Initiative will deliver an interim report on the cohort in September 2015. Dr. Green said that, in coordination with the White House and other U.S. Government agencies, the NIH anticipates announcing specific funding opportunities in fall 2015, with initial awards to be made in October 2016. Trans-NIH collaboration and funding may also be possible through the NIH Common Fund and Big Data to Knowledge (BD2K) initiative. In addition, there will be opportunities for private-sector participation and partnership with government (e.g., with Apple Inc.) Dr. Green emphasized that transparency will be assured throughout as all activities and events, and all requests for information, will be posted on the NIH website for the initiative (www.nih.gov/precisionmedicine).
In closing, Dr. Green commented that precision medicine is "all the rage" in the media and while much is not known, it is the "right thing" to do. He noted that the NIH leadership is comfortable with the uncertainty surrounding the initiative thus far, for it was in the same situation 25 years ago, in 1990, when the Human Genome Project was launched.
In response to the Council's questions about the national cohort, Dr. Green said that establishing a cohort that is representative of the U.S. population is a high priority and that inclusion of children is being actively discussed. He also noted that the NIH will draw on the expertise and experience of patient advocacy groups, particularly with respect to rare diseases, and anticipates sharing data with international data banks such as the UK Biobank.
Dr. Somerman commented on the continuing struggle to include dental health records in medical EHRs. She suggested that the Precision Medicine Initiative could be viewed as an opportunity to overcome the existing barriers and to galvanize the change that is needed.
VII. PRECISION ORAL HEALTH RESEARCH AT NIDCR
Dr. Somerman reported on NIDCR efforts to advance precision oral health care through research. She presented an overview of precision medicine in the NIDCR extramural portfolio and NIDCR Strategic Plan: 2014-2019, examples of NIDCR-supported precision health research, and a list of NIDCR-supported cohort studies and multi-institute collaborations that could contribute to the national research cohort envisaged for the Precision Medicine Initiative.
Dr. Somerman noted the many different areas in the NIDCR's FY 2014 extramural portfolio that align with the President's Precision Medicine Initiative. These include, for example, translational genomics, tissue engineering and regenerative medicine, dental and other biomaterials, salivary biology and immunology, developmental biology and genetics, and health disparities. She noted that Goal II of the NIDCR Strategic Plan is to "enable precise and personalized oral health care through research." Dr. Somerman commented on the different terms used for precision medicine (e.g., personalized or individualized medicine, genomic medicine) and said that they all refer to precision health care, "an emerging approach for disease prevention and treatment that takes into account people's individual variations in genes, environment, and lifestyle." Dr. Somermati noted that the NIH already facilitates this research through its NIH Genomic Data Sharing policy, which was issued in final fonn in 2014 and serves both to accelerate translation of data into knowledge and to protect the privacy of research participants. She further noted that at the March 2015 House Appropriations Committee Hearing on the NIH Budget, Dr. Francis Collins stated that dental caries and periodontal diseases would be included in the Precision Medicine Initiative.
Dr. Somerman highlighted 10 of the research opportunities in precision medicine that the NIDCR supports. These are as follows:
- The National Dental Practice-Based Research Network. This network comprises six regional research centers, involves almost 5,000 practitioners who are addressing oral health care issues that have an immediate impact for the more than 29,000 individuals enrolled, and has collected blood samples from all enrollees.
- BigMouth. This open-access multi-institutional dental data repository (EHRs) is funded in partnership with axiUm and, as the largest oral health research database, contains standardized diagnostic dental data from more than 1 million patients.
- FaceBase and 3-dimensional craniofacial imaging. In this coordinated extramural-intramural effort, researchers are collecting genomic and gene expression data along with facial imagery to identify genetic changes and evaluate genetic mechanisms of craniofacial development and disorders.
- GWAS of CL/P. Investigators are identifying candidate genes for CL/P, the most commonly occurring craniofacial birth defect, and setting the stage for translation from animal research to human studies.
- Cancer biology. NIDCR researchers are moving most rapidly toward precision medicine in this area, focusing on head and neck cancers and human papillomavirus (HPV)-related oropharyngeal cancer, which accounts for 37 percent of HPV-associated cancers. Through stratification of patients using genetic-based methods, the goal is to combine targeted therapy with companion diagnostic tests for all cancers.
- Temporomandibular joint disorders (TMDs). Three specific NIDCR initiatives for research on TMDs, which are associated with severe orofacial pain, are: Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA); an upcoming clinical trial to determine whether a genetic variation modifies patients' response to the beta-blocker propranolol; and studies of the pharmacogenomics of orofacial pain management.
- Advances in salivary diagnostics. The research advances, which include tests that are already on the market, non-invasive brush biopsy, and tissue arrays, have strong potential applicability for diagnosis and treatment of periodontal disease, caries, cancer, heart disease, Sjögren's syndrome, and post-traumatic stress disorder.
- The oral microbiome. This area is one of five selected for the Trans-NIH Human Microbiome Project. The research, which is generating a huge amount of information important for targeted diagnosis and treatment, includes development of the Human Oral Microbiome Database and definition of difficult-to-cultivate bacterial communities.
- Genetics of dental caries. Research is focused on several genes that have a potential biologic role in caries and on the effects of enamel matrix genes on caries, as moderated by fluoride exposure.
- Precision periodontal research. The aim is to ascertain biomarkers of periodontal disease progression and to identify early markers of aggressive periodontitis.
Dr. Somerman cited four cohort and collaborative studies which are funded by the NIDCR and offer significant opportunities for research collaboration and integration in the President's Precision Medicine Initiative. These are:
- OPPERA, in which researchers are (a) monitoring the development of TMD and (b) determining genetic risk factors for TMD in a cohort of more than 2,700 healthy men and women.
- COHRA I and II: Center for Oral Health Research in Appalachia, in which researchers are (a) analyzing psychosocial, genetic, and microbial risks for childhood caries and (b) identifying factors underlying oral health disparities in a cohort of pregnant women.
- The Iowa Bone Development Study, in which scientists are (a) studying the effects of diet, physical activity, and fluoride exposure on bone development and (b) identifying genes involved in bone mineralization, matrix structure, and growth in a cohort of children from birth through adolescence.
- The Pediatric HIV/AIDS Cohort Study (PHACS), a multi-institute-funded effort in which investigators are studying (a) the effects of perinatal HIV infection and antiretroviral therapy on growth, development, and maturation of children and (b) the genetics and epigenetics of HIV infection and treatment in a cohort of children and adolescents.
In closing, Dr. Somerman commented on the enthusiasm for precision medicine, as well as precision dentistry, and remarked that it is "an incredibly exciting time to be in research and practice."
VIII. ADJOURNMENT OF OPEN SESSION
Dr. Somerman adjourned the open session of the Council meeting at 12:38 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).
IX. REVIEW OF APPLICATIONS
The Council considered 549 applications requesting $148,413,123 in total costs. The Council recommended 385 applications for a total cost of $107,994,170 (see Attachment II).
The meeting was adjourned at 1:57 p.m. on May 20, 2015.
I hereby certify that the foregoing minutes are accurate and complete.
Dr. Martha J. Somerman
National Advisory Dental and
Craniofacial Research Council
Dr. Alicia Dombroski
National Advisory Dental and
Craniofacial Research Council
I. Roster of Council Members
II. Table of Council Actions