NIDCR WELCOMES NEW DIRECTOR
The NIDCR is delighted to welcome Martha J. Somerman, D.D.S., Ph.D., as the eighth Director of the Institute. Dr. Somerman began her duties as NIDCR Director on August 29, 2011. She was officially sworn in by NIH Director Francis S. Collins at noon on August 31st. Dr. Somerman comes to the NIDCR from the University of Washington School of Dentistry, Seattle, where she served as dean since 2002.
ACTIVITIES OF THE NIDCR DIRECTOR
Since her arrival at the end of August, Dr. Somerman has been taking part in NIH leadership meetings and holding a series of overview and program briefing meetings with staff from NIDCR’s Office of the Director, Division of Extramural Research, Division of Extramural Activities, and Division of Intramural Research.
On August 31st, the NIDCR Director participated in a meeting of NIH leadership with Senator Ben Cardin (D.–MD). The following week, she attended the NIH Leadership Forum held on September 8th.
Dr. Somerman will travel to Japan early in October to deliver the keynote address at the 4th Hiroshima Conference on Education and Science in Dentistry. The title of her talk is “Personalized Medicine: Is Dentistry Ready?” The conference will be held concurrently with the 59th Annual Meeting of the Japanese Association for Dental Research.
Dr. Somerman’s committee memberships include co-chairing the NIH Pain Consortium and serving as a member of the newly established Interagency Pain Research Coordinating Committee (IPRCC). The IPRCC, established through the Patient Protection and Affordable Care Act, has been tasked with developing a summary of advances in pain care research supported or conducted by Federal agencies and identifying critical gaps in research on the symptoms and causes of pain. In addition, the committee is charged with making recommendations on how to: reduce unnecessary duplication of effort among Federal agencies; disseminate information on pain care; and expand partnerships between public and private entities to increase collaborative, cross-cutting research.
ACTIVITIES OF THE NIDCR DEPUTY DIRECTOR
NIDCR Deputy Director Isabel Garcia continued to serve as Acting Director of the Institute through the end of August. Since the last meeting of the NADCRC, she has delivered presentations at scientific conferences and meetings, spoken to patient advocate organizations, provided updates about the Institute to dental professional associations, and served on PHS and HHS-level committees. She also took part in several activities for dental students.
On June 28, Dr. Garcia, together with Dr. Amy Adams, director of the NIDCR Office of Science Policy and Analysis, and Dr. Lawrence Tabak, NIH Principal Deputy Director, attended a pre-release briefing on the Institute of Medicine’s (IOM) report on pain research, care, and education, entitled “Relieving Pain in America: A Blueprint for Transforming Prevention, Care, Education, and Research.” Dr. Phillip Pizzo, IOM committee chair, Dr. Noreen Clark, vice chair, and four additional committee members briefed NIH on their findings and recommendations before the report was publicly released.
At the request of Dr. Tabak, Dr. Garcia attended the 3rd meeting of the HHS Secretary’s Tribal Advisory Committee, held September 13-14 in Washington, D.C. Dr. Garcia has been asked to serve as the NIH point of contact for all activities related to this committee, whose purpose is to keep the HHS Secretary apprised on matters related to American Indians and Alaska Natives.
Dr. Garcia also attended a meeting of the PHS Oral Health Coordinating Committee with Dr. Howard Koh, Assistant Secretary for Health, HHS, on August 18. Also representing NIH was Dr. Renee Joskow from the National Center for Research Resources; other attendees included representatives from eight HHS operating divisions, the Office of the Secretary, and the U.S. Coast Guard. The purpose of the meeting was to brief Dr. Koh on a number of initiatives being carried out within HHS that are of key relevance to oral health, including the two recent IOM reports--“Advancing Oral Health in America” and “Relieving Pain in America”-- and the report on Oral Health Strategy from the Centers for Medicare and Medicaid Services. An annual report and summaries from each agency were prepared and highlights presented at the meeting.
Dr. Garcia also delivered two addresses at scientific meetings focused on chronic pain. On June 6, she gave the opening remarks at the 6th Scientific Meeting of the Temporomandibular Joint (TMJ) Association held in Bethesda, MD. The theme of the meeting was “Comorbid Chronic Pain Conditions – Mechanisms, Diagnosis, and Treatments.” The meeting focused on pathophysiological processes underlying chronic pain conditions that co-exist with TMD and constitute comorbid chronic pain conditions. On July 11, she gave a talk entitled “Setting a Research Agenda for a Chronic Pain Condition: NIDCR and Temporomandibular Joint Disorders” at a conference convened by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) to develop a research agenda for vulvodynia as a chronic pain condition. Vulvodynia is among the chronic pain conditions of interest to the Chronic Pain Research Alliance (in addition to temporomandibular joint disorders, chronic fatigue syndrome, and endometriosis). The Chronic Pain Research Alliance is a group of independent nonprofit organizations that seeks to advance the scientific, medical and policy needs of individuals affected by medical conditions that frequently overlap.
Other talks given by the NIDCR Deputy Director included delivering the keynote address on July 25 at the 2011 North American Craniofacial Family Conference (NACFC), held in Las Vegas, NV. Her presentation was entitled “NIDCR and NIH Research Relevant to Persons with Facial Differences.” The conference was supported by AmeriFace, an organization devoted to providing information and support to individuals whose facial differences are present at birth, as well as those who have acquired facial differences as a result of illness, disease or trauma, such as stroke, cancer, accident and burns. In addition, Dr. Garcia gave a taped interview on May 25 designed to be included in a video tribute honoring Ms. Mary Kaye Richter, founder of the National Foundation for Ectodermal Dysplasias, on the occasion of her retirement after 30 years of leading the ectodermal dysplasias community.
On July 13, the NIDCR Deputy Director provided a brief update about NIDCR activities to the American Dental Association’s Council on Scientific Affairs. Topics included the short-term budgetary outlook, proposed and ongoing NIDCR scientific initiatives, and selected examples of significant findings.
Finally, Dr. Garcia served as a panelist in NIDCR’s annual summer trainee panel discussion entitled, "Future Careers in Research and Dentistry,” which was held July 7. Other panelists included Drs. Matthew Hoffman and Ana Cotrim from NIDCR’s intramural program and Dr. Leslie Frieden, NIDCR’s extramural training officer. Dr. Deborah Philp, director, NIDCR Office of Education, moderated the event. The following day, NIDCR hosted dental students participating in the American Student Dental Association’s summer externship program. Brian Sodergren, manager of ADA’s Grassroots Education, accompanied the students as they toured the Clinical Center, visited the National Library of Medicine, met with NIDCR’s dental public health residents, and heard an overview about NIDCR from Dr. Garcia.
The FY 2011 Appropriation provided $409.6 million for NIDCR.
The President’s Budget Request would provide $420.4 million for NIDCR. The complete NIDCR budget justification to Congress is available at:
It is expected that NIDCR and the rest of NIH will begin FY 2012 under a continuing resolution with the resulting appropriation at levels that are possibly flat or below what was received for FY 2011.
HHS Tightens Financial Conflict of Interest Rules for Researchers
HHS has issued an updated Final Rule on conflict of interest that provides a framework for identifying, managing, and ultimately avoiding investigators’ financial conflicts of interest. NIH staff worked with HHS to revise the 1995 regulations to update and enhance the objectivity and integrity of the research process.
The regulations will be implemented no later than 365 calendar days after publication of the Final Rule in the Federal Register; the rule was published on August 25th.
Major changes to the regulations include the definition of significant financial interest (SFI), the extent of investigator disclosure, the information reported to the Public Health Service (PHS) awarding component, the information made accessible to the public, and investigator training. The revised regulations:
- Require investigators to disclose to their institutions all of their significant financial interests related to their institutional responsibilities.
- Lower the monetary threshold at which significant financial interests require disclosure, generally from $10,000 to $5,000.
- Require institutions to report to the PHS awarding component additional information on identified financial conflicts of interest and how they are being managed.
- Require institutions to make certain information accessible to the public concerning identified SFIs held by senior/key personnel.
- Require investigators to complete training related to the regulations and their institution’s financial conflict of interest policy.
Additional details about the major changes to the regulations can be found at: http://grants.nih.gov/grants/FCOI_Final_Rule_inspection_Desk.pdf
Also see the Financial Conflict of Interest website:
NIH-Commissioned Study Identifies Gaps in NIH Funding Success Rates for
Black applicants from 2000-2006 were 10 percentage points less likely than white applicants to be awarded research project grants from the NIH after controlling for factors that influence the likelihood of a grant award, according to an NIH-commissioned study in the journal Science. In an accompanying commentary, NIH Director Francis Collins, M.D., Ph.D., and Principal Deputy Director Lawrence Tabak, D.D.S, Ph.D., call the findings unacceptable and commit to immediate action by the NIH.
NIH initiated the study in 2008 to determine if researchers of different races and ethnicities with similar research records and affiliations had similar likelihoods of being awarded a new NIH research project grant (R01). The study, which also received funding from the National Science Foundation, was conducted by researchers at the University of Kansas, Discovery Logic/Thomson Reuters, and NIH. It found that typical measures of scientific achievement did not translate to the same level of application success for black applicants. The study controlled for education, citizenship, country of origin, training, employer characteristics, prior research awards, and publication record. Although Asian applicants also were less likely to receive an award than white applicants, those differences disappeared when the sample was limited to U.S. citizens. Award probability for Hispanic applicants did not differ significantly from white applicants.
The study is part of a larger effort by NIH to examine and improve the diversity (including race, ethnicity, gender, age, disabilities, and socioeconomic status) of its funded biomedical research workforce. This study focused solely on race and ethnicity since there are few studies on the racial and ethnic composition of federal research funding applicants. The study provides a solid benchmark for further studies of grant success rates and against which progress can be measured.
Also of concern to NIH is the low number of applications for NIH R01 grants from non-white applicants. Of the 40,069 individual applicants included in the 2000 to 2006 study, 1.5 percent self-identified as black or African-American (598), 3.3 percent as Hispanic (1,319), 13.5 percent as Asian (5,402), 71 percent as white (28,456), and 11 percent as other/unknown. These figures are consistent with data showing that the number of underrepresented populations in the fields of science and medicine remains small.
NIH has developed and is implementing a framework for action to: increase the number of early career reviewers, including those from underrepresented populations; examine the grant review process for bias and develop interventions; improve support for grant applicants; and gather expert advice on additional action steps.
Dr. Collins’ statement about diversity is found at:
Working Group on Future of Biomedical Research Workforce Requests Input
The working group established by the Advisory Committee to the NIH Director (ACD) to examine the future of the biomedical research workforce in the U.S. is seeking input from the extramural community to ensure a thorough and comprehensive evaluation of the issues involved. Comments are sought from students, postdoctoral fellows, scientists, scientific societies, and NIH grantee institutions, as well as from the general public, and should be submitted electronically by October 7, 2011 to: http://grants.nih.gov/grants/guide/rfi_files/bmw/add.cfm
The working group, which will recommend actions to the ACD and to the NIH Director, is charged with developing a model for a sustainable, diverse, and productive U.S. biomedical research workforce. The model will help inform decisions about how to train the optimal number of people for the appropriate types of positions that will advance science and promote health.
In its initial deliberations, the working group identified the following issues as important to consider when developing a model of the future biomedical research workforce: the balance between supply (including the number of domestic and foreign trained PhDs and post-docs) and demand, i.e. post-training career opportunities; characteristics of PhD training in biomedical research; characteristics of clinician-research training; length of postdoctoral training; the ratio of PhD students and postdoctoral fellows on training grants to those supported by research grants; possibilities for professional/staff scientist positions and the level of training required for such positions (e.g. PhD or MSc degrees); issues related to the attractiveness of biomedical research careers (e.g. salary, working conditions, availability of research funding); and the effect of changes in NIH policies on investigators, grantee institutions and the broader research enterprise.
NIH Blueprint Empowers Drug Development for Nervous System Disorders
NIH has made awards to investigators across the U.S. for an ambitious set of projects seeking to develop new drugs for disorders of the nervous system. The projects — aimed at treating conditions such as vision loss, neurodegenerative disease and depression — are funded through the NIH Blueprint for Neuroscience Research. The Blueprint is a cooperative effort among 16 NIH Institutes, Centers and Offices that support neuroscience research, including the NIDCR. The NIH Blueprint leverages their resources to confront major, cross-cutting challenges in neuroscience research.
The awards were made to seven research teams at six academic institutions and one drug discovery company. Detailed information about the projects is available at http://www.neuroscienceblueprint.nih.gov/bpdrugs/bpn.htm.
NIH Launches Medical Research Scholars Program
A new Medical Research Scholars Program for medical and dental students will begin in September 2012 in Bethesda, Maryland, NIH has announced. The program will offer research experiences with intramural investigators from across NIH in basic science laboratories, and in clinical and translational research conducted at the NIH Clinical Center. The program is made possible through a partnership with the Foundation for the National Institutes of Health supported by a grant from Pfizer Inc and contributions from the Howard Hughes Medical Institute.
Program applications will be accepted October 1, 2011 through mid-January 2012. About 40 students are expected to be admitted during the program’s first year. The goal is to accept up to 70 students as the program grows. Support for selected students will include a stipend and resources for education enrichment, such as travel to scientific meetings.
NIH Director’s 2012 Pioneer Award and New Innovator Award Programs Now Accepting Applications
NIH welcomes proposals for the 2012 NIH Director's Pioneer Awards and New Innovator Awards for innovative approaches to major challenges in biomedical or behavioral research. Pioneer Awards provide up to $2.5 million in direct costs over 5 years and are open to scientists at any career stage. New Innovator Awards provide up to $1.5 million in direct costs over 5 years and support exceptionally creative new investigators with highly innovative research ideas at an early stage of their career when they may lack the preliminary data required for an R01 grant. See additional information about the programs:
2012 NIH Director’s Pioneer Award Program (DP1):
2012 NIH Director’s New Innovator Award Program (DP2):
NIH Releases Best Practices for Combining Qualitative and Quantitative Research
NIH has released best practices for scientists conducting mixed methods health research--research that combines the strengths of both quantitative and qualitative research. Despite the increased interest in mixed methods research in health fields and at NIH, prior to this report, there was limited guidance to help scientists developing applications for NIH funding that featured mixed methods designs, nor was there guidance for the reviewers at NIH who assess the quality of these applications. Additional information about Best Practices for Mixed Methods Research in the Health Sciences is found at:
Computational Method Predicts New Uses for Existing Medicines
For the first time, scientists are using computers and genomic information to predict new uses for existing medicines. An NIH-funded computational study analyzed genomic and drug data to predict new uses for medicines that are already on the market. The results were reported in the August 17 online issue of Science Translational Medicine. The scientists drew their data from the NIH National Center for Biotechnology Information Gene Expression Omnibus, a publicly available database that contains the results of thousands of genomic studies on a wide range of topics, submitted by researchers across the globe. The resource catalogs changes in gene activity under various conditions, such as in diseased tissues or in response to medications. The research group focused on 100 diseases and 164 drugs.
NIH-Funded Research Network to Explore Oil Spill Health Effects
An NIH-funded network of researchers will evaluate potential harmful effects of the Deepwater Horizon disaster on reproduction and birth outcomes, the cardiorespiratory system, and behavior and mental health. The network of community and university partnerships, under the leadership of NIH’s National Institute of Environmental Health Sciences (NIEHS), will conduct research to evaluate the level of potentially harmful contaminants in air, water, and seafood, and assess their relationship to health outcomes.
The five-year, $25.2 million program will support population-based and laboratory research at Louisiana State University Health Sciences Center New Orleans; Tulane University, New Orleans; the University of Florida, Gainesville; and The University of Texas Medical Branch at Galveston. In contrast to NIEHS’ Gulf Long-term Follow-up Study, known as the GuLF Study, which is focused on the oil spill cleanup workers and volunteers, this new research will concentrate on the range of acute and long-term health effects to the general public.
National Children’s Study Upgrading Data Gathering, Analysis
The National Children’s Study is changing its approach to informatics—the science of classifying, cataloging, storing, analyzing, and retrieving information, study officials have announced. The new approach, termed facilitated decentralization, seeks to test a variety of different yet compatible information systems to identify those that will best meet the needs of the multi-site study. The National Children’s Study is examining the effects of environment and genetics on the growth, development and health of children across the United States, from pre-conception to age 21. Study officials invite interested researchers in the federal government and in research institutions to collaborate on new informatics components to be integrated into the study’s main informatics system.
Dr. Judith Greenberg Named Acting Director of the National Institute of General Medical Sciences
NIH Director Francis S. Collins has named Judith H. Greenberg, Ph.D., as acting director of the National Institute of General Medical Sciences (NIGMS) while the search continues for a permanent director. A developmental biologist by training, Dr. Greenberg has directed the NIGMS Division of Genetics and Developmental Biology since 1988. She replaces NIGMS Director Jeremy M. Berg, Ph.D., who left in June.
Leadership Transition at the National Center for Research Resources
Barbara Alving, M.D., Director of the National Center for Research Resources (NCRR), will leave the NIH on September 30th. Dr. Alving has been NCRR Director since 2007 and previously served as the Institute’s Acting Director. From 2003-2005, she was Acting Director of the National Heart, Lung, and Blood Institute.
Dr. Louise Ramm, Deputy Director and Director of Extramural Activities for NCRR, will become the Institute’s Acting Director on October 1st. Dr. Ramm has been with NCRR since 1987 when she joined the Division of Research Resources, the Institute’s predecessor organization.
Dr. Antonio Scarpa Retires; Dr. Richard K. Nakamura Appointed CSR Acting Director
Dr. Antonio Scarpa, Director of the Center for Scientific Review, retired on September 2 after serving six years in the position. CSR receives all--and reviews most--of the over 80,000 grant applications researchers send to NIH each year.
While a search is under way for a new director, Richard K. Nakamura, Ph.D., has been appointed Acting Director of the CSR. Dr. Nakamura has served at the National Institute of Mental Health (NIMH) as both Scientific Director and Deputy Director. He also was NIMH Acting Director from 2001 to 2002.
Director of New Intramural Center for Regenerative Medicine Appointed
Dr. Collins has announced the appointment of Mahendra S. Rao, M.D., Ph.D. as director of the new NIH Intramural Center for Regenerative Medicine (NIH-CRM). The NIH-CRM is an initiative to create a world-class center of excellence in stem cell technology on the NIH campus, including induced pluripotent stem cells (iPSC), which can have applications in many systems and organs of the body. A major goal for the center is to build upon existing NIH investments in stem cell research to advance translational studies and ultimately cell-based therapies in the NIH Clinical Center. The center will also serve as a resource for the scientific community, providing stem cells, as well as the supporting protocols and standard operating procedures used to derive, culture, and differentiate them into different cell types. The center is an initiative of the NIH Common Fund.
Dr. Rao is internationally renowned for his research involving human embryonic stem cells (hESCs) and other somatic stem cells. He has worked in the stem cell field for more than 20 years, with stints in academia, government and regulatory affairs and industry.
Death of Former NIH Director Bernadine Healy
It is with great sadness that we report the death of former NIH Director Bernadine P. Healy on August 6. The first woman to lead the NIH, Dr. Healy served as Director from 1991-1993. Under her leadership the Women's Health Initiative was launched, the most definitive, far-reaching clinical trial of women's health ever undertaken in the United States. It focused on strategies for preventing heart disease, osteoporosis, breast cancer, and colorectal cancer--major causes of death and disability in postmenopausal women. To better understand the different ways that diseases and treatments affect men and women, Dr. Healy also established a policy that all NIH-funded clinical trials on conditions that affect both genders must include both men and women.
Dr. Healy was a strong supporter of the effort to sequence the human genome. In addition, she recognized the promise of genomics by establishing an intramural genomic research program at NIH.
Status of Evaluation of 2009-2013 NIDCR Strategic Plan
Evaluation of the 2009-2013 NIDCR Strategic Plan is under way, led by Dr. Sue Hamann, science evaluation officer in NIDCR’s Office of Science Policy and Analysis (OSPA). Drs. Rena D’Souza and Pamela Den Besten are the NIDCR Council representatives to the evaluation and have contributed greatly to the evaluation plan. Dr. Eneida Mendonça (recommended by Council member Dr. Kyungmann Kim) is working with OSPA evaluation staff as a bioinformatics consultant. We would also like to thank Dr. Clif Carey of the Paffenbarger Research Center for his comments on the evaluation plan.
The small studies about NIDCR’s links to the Plan in official documents and comparison of our Plan to the strategic plans of other NIH ICs have been completed. The Division of Extramural Research is preparing a report that links every FY2010 newly funded award to goals and objectives in the Plan. Additional input will be sought from Council members via an electronic survey and from various stakeholders and stakeholder groups through interviews.
A written report will be prepared for the January 2012 NADCRC meeting.
Training and Career Development News
NIDCR Welcomes Two New Dental Public Health Residents
Another eventful year in NIDCR’s Residency Program in Dental Public Health ended with the successful completion of the program by Diego Capurro, D.D.S., M.P.H., and Khushdeep Malhotra, B.D.S., M.P.H. Dr. Capurro has returned to the health ministry in his native Paraguay and Dr. Malhotra is beginning a fellowship with the David Satcher Health Leadership Institute in Atlanta.
On July 1, NIDCR welcomed two new dental public health residents-- Evelyn Lucas-Perry, D.D.S., M.P.H. and Aderonke (‘Ronke’) Akinkugbe, B.D.S., M.P.H. Dr. Akinkugbe comes to the program from Salt Lake City, UT, where she served as an oral health prevention specialist at the State Department of Health. She earned her M.P.H. at the Johns Hopkins Bloomberg School of Public Health in Baltimore, MD, and her B.D.S. from the University of Lagos, Nigeria. Dr. Perry recently completed a dual D.D.S./M.P.H. program at the University of Michigan. She holds a leadership position in the National Dental Association and is on the Board of Directors of the American Dental Education Association.
Advanced Training Institute on Health Behavior
NIDCR staff are collaborating with the National Cancer Institute and other NIH institutes and centers in refining the curriculum for the upcoming Advanced Training Institute on Health Behavior Theory (ATI). The July 2010 ATI, which was held in Madison, WI, was co-sponsored by the NIDCR and included a strong oral health research community presence. The seminar provided intensive training for investigators in the conceptual, methodological, and statistical underpinnings of health behavior theory. NIDCR hopes to continue its involvement in the ATI planned for July 2012. The Institute will announce when applications to attend the ATI are available. NIDCR also will encourage investigators to apply whose work integrates health behavior theory.
T32 and T90/R90 Awards
After extensive Council discussion regarding the goals and direction of the Institute’s training programs, NIDCR introduced the new T32 and T90/R90 Institutional Training Grant FOAs in 2010. In response to these FOAs, NIDCR made three T32 awards and five T90/R90 awards in FY2011. Two of the T90s were awarded to dental schools that did not have ongoing NIDCR comprehensive T32 programs.
NIH Loan Repayment Programs
The NIH Loan Repayment Programs (LRPs) encourage promising researchers and scientists to pursue careers in biomedical, behavioral, social and clinical research by repaying up to $35,000 of their qualified student loan debt each year. NIDCR participates in the Clinical and Pediatric LRPs. This year, the Institute funded 9 clinical and 4 pediatric LRP contracts.
Supplement Programs to Promote Diversity in Health-Related Research and to Promote Reentry into Biomedical and Behavioral Research Careers
The administrative Supplement Programs to Promote Diversity in Health-Related Research and to Promote Reentry into Biomedical and Behavioral Research Careers are viewed as career development and training experiences for eligible candidates. Assessment of applications for these supplements is shared among NIDCR’s Research Training and Career Development Branch, Grants Management Branch, and Division of Extramural Research. In FY2011, NIDCR awarded seven Diversity supplements and two Reentry supplements.
The following awardees and trainees have received their first R01s:
- Current NIDCR K08 awardee, Ana Bedran-Russo, D.D.S., M.S., Ph.D.
(R01 DE021040) “Biomodification of Dentin Matrix Structure.” Dr. Bedran-Russo is an assistant professor in the Department of Restorative Dentistry and director of the Applied Dental Materials and Interfaces Laboratory at the University of Illinois, Chicago.
- Former NIDCR K22 awardee, Deborah Hogan, Ph.D.
(R01 AI091702) “Host-associated regulation of P. aeruginosa colonization and virulence.” Dr. Hogan is an associate professor in the Department of Microbiology and Immunology at Dartmouth Medical School.
- Former NIDCR T32 predoctoral trainee, Nancy Maserejian, Sc.D.
(R01 ES019155) “Health Effects of Dental Composites in Children.”
Dr. Maserejian received her Ph.D. in epidemiology from the Harvard School of Public Health through the Forsyth Institute NIDCR T32 training grant. She is a research scientist at New England Research Institutes, Inc.
- Former NIDCR T32 postdoctoral trainee, Hiroaki Misono, Ph.D.
(R01-NS067207) “Kv Channel Trafficking in Neuronal Dendrites.” Dr. Misono is an assistant professor in the Department of Neural and Pain Sciences at the University of Maryland Baltimore.
- Former NIDCR T32 postdoctoral trainee, Lyudmila Vulchanova, Ph.D.
(R01 DE021996) “VGF, Critical Role in the Transition from Acute to Chronic Pain.” Dr. Vulchanova is the contact PI for this multi-PI project (Vulchanova, Salton), which was awarded under the NIH Blueprint for Neuroscience Research Grand Challenge on the Transition from Acute to Chronic Neuropathic Pain. Dr. Vulchanova is a research assistant professor in the Department of Veterinary and Biomedical Sciences, University of Minnesota.
K99 awardee Cuong Nguyen, Ph.D., has successfully transitioned to the independent R00 phase of his award by accepting a tenure track position as assistant professor in the Department of Infectious Diseases and Pathology at the College of Veterinary Medicine, University of Florida. His R00 research project is entitled, “Immune-pathophysiology of lymphocytic foci in Sjögren's syndrome.”
Former NIDCR F32 awardee, Rebecca Fox, Ph.D., has received a NIDCR K99/R00 pathway to independence award entitled, “Drosophila salivary gland, a model for studying the molecular basis of secretion.” Dr. Fox is a postdoctoral fellow in the Department of Cell Biology at Johns Hopkins University School of Medicine.
Transition to NRSA Fellowships
One of the goals of the Research Training and Career Development Branch is to encourage trainees to move from institutional training positions to independent funding. Several trainees on NIDCR institutional training grants have successfully transitioned to individual NRSA fellowships. Six dual-degree Dentist Scientist Training Program trainees on NIDCR T32 institutional training grants-- Ami Amini at the University of Connecticut Health Center, Amanda Buff at the Medical University of South Carolina, Benjamin Chaffee, Alice Goodwin and Kyle Jones at the University of California, San Francisco, and Stephanie Nunez at the University of Michigan at Ann Arbor-- have successfully applied for and been awarded NIDCR F30 fellowships. Dana Catalfamo, a predoctoral Ph.D. trainee on an NIDCR institutional training grant at the University of Florida, was awarded an NIDCR F31 fellowship. Elaine Por, a NIDCR T32 trainee at the University of Texas Health Science Center, San Antonio, was awarded a predoctoral NIDCR F31 fellowship to promote diversity in health related research. Finally, Andrew Tarr, a postdoctoral trainee at Ohio State University, was awarded an NIDCR F32 fellowship.
2011 NIDCR Summer Research Program
The 2011 NIDCR Summer Research Program included a diverse group of 41 participants, including dental (34%), medical (5%), graduate (2%), undergraduate (39%), and high school students (20%). Sixty-one percent were female. In terms of ethnicity, Asian Americans were the largest group represented among the students (49%), followed by Caucasians (37%), African Americans (5%) and Hispanic/Latino students (2%).
Included among the participants were 14 NIDCR Summer Dental Student Award recipients (see following item). In addition, there were three summer interns who were volunteers.
NIDCR Summer Dental Student Award Program
The 2011 NIDCR Summer Dental Student Award Program hosted 14 awardees selected from schools across the U.S. Advertisements about this award were posted in newsletters from the American Dental Association, the American Dental Education Association, and the American Student Dental Association. Paper and electronic mailings were also sent to all accredited dental schools encouraging students to apply for training opportunities at NIDCR.
The 14 Summer Dental Student Award recipients came from the following schools: Howard University College of Dentistry; University of Pennsylvania School of Dental Medicine; Harvard University School of Dental Medicine; University of Connecticut School of Dental Medicine; University of Minnesota School of Dentistry; Tufts University School of Dental Medicine; University of California San Francisco School of Dentistry; University of North Carolina School of Dentistry; Texas A&M Health Science Center Baylor College of Dentistry; and University of Medicine and Dentistry of New Jersey. Highlights of this year’s activities included the summer student research welcome reception, a career panel discussion on “Future Careers in Research and Dentistry,” a field trip to the Samuel D. Harris National Museum of Dentistry in Baltimore, MD, a visit to the University of Maryland, Baltimore Dental School to hear research presentations from dental students participating in their program, oral presentations by some of the NIDCR summer dental students, and participation in the NIDCR summer intern poster session.
Grant Writing Seminar
On July 22nd, together with the Eunice Kennedy Shriver National Institute of Child Health & Human Development and the National Human Genome Research Institute, NIDCR co-hosted its annual grant writing seminar for postdocs. The morning session focused on a successful research grant and key changes in the preparation of NIH applications. The second session dealt with developing specific aims. To participate in this session, trainees had to submit specific aims that were then critiqued by the session leader. Attendees found these sessions useful and expressed an interest in seeing more sessions like this offered at NIH.
NIDCR Fellows Retreat
The DIR Office of Education hosted its 5th annual NIDCR fellows’ retreat at Rocky Gap in Cumberland, MD. The two-day event provided an opportunity for postdoctoral fellows, staff scientists, graduate students and post-baccalaureate IRTAs to share their research and present their work to their peers. In addition to oral presentations and poster sessions, the retreat included three workshops. Dr. Sharon Milgram, director of the NIH Office of Intramural Training and Education (OITE), led a workshop entitled, “How to Negotiate a Job Offer;” Dr. Shawn Mullen, deputy director of postdoctoral services at OITE, led a workshop on “How to Give a Successful Job Talk;” and Dr. Patricia Phelps, deputy director of the OITE Graduate Partnerships Program, led a concurrent Pre-IRTA trainee workshop entitled, “Keys to Career Success; Networking, Time Management and Mentors.” This was the first time that a pre-IRTA workshop was offered at the retreat. Feedback on the event was positive and fellows found the topics helpful; all indicated that they would attend again next year.
In an effort to promote oral health internationally, the DIR Office of Education supplied informational resources to an elementary school and high school in Bagamoyo, Tanzania. Emily Pinnow, a pre-dental student who is an NIDCR pre-IRTA, was invited to visit these schools while on vacation in Tanzania. Ms. Pinnow shared best oral health practices with students and faculty of the schools, along with pamphlets on oral health. She also used exercises from the “Open Wide and Trek Inside” supplemental series (published by NIDCR) to explain the importance of oral health to the students. In turn, she learned about common oral health practices in Tanzania.
Meetings, Conferences, and Lectures
Upcoming Lecture: Ambassador Eric Goosby to Present 2011 David E. Barmes Global Health Lecture
Dr. Eric Goosby, U.S. Global AIDS Coordinator, will present the 2011 David E. Barmes Global Health Lecture on Tuesday, December 13th in the Masur Auditorium (Bldg. 10) on the NIH campus.
Ambassador Goosby has over 25 years of experience with HIV/AIDS, ranging from his early years treating patients at San Francisco General Hospital when AIDS first emerged, to engagement at the highest level of policy leadership. As the leader of all U.S. government international HIV/AIDS efforts, he oversees implementation of the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), in addition to government participation with the Global Fund to Fight AIDS, Tuberculosis and Malaria. Together with the heads of the U.S. Agency for International Development and the Centers for Disease Control and Prevention, he also serves on the operations committee that leads the U.S. Global Health Initiative.
Jointly sponsored by NIDCR and the Fogarty International Center, the annual lecture series honors the late David E. Barmes, a longstanding World Health Organization employee, special expert for international health at NIDCR, and ardent spokesman for global health.
Past Meetings and Conferences:
The 6th TMJ Association Scientific Meeting
On June 5-7, the 6th Temporomandibular Joint (TMJ) Association Scientific Meeting was held in Bethesda, MD. Dr. John Kusiak, director of the DER Molecular and Cellular Neuroscience Program, participated in the organization and planning of this meeting and gave a brief presentation about recent NIH Pain Consortium activities. The meeting was supported through an NIDCR Conference and Scientific Meetings (R13) grant.
Tailoring and Targeting Behavioral and Social Interventions: Weaving a Strategy for Effective and Efficient Intervention Research
Staff from the Behavioral and Social Sciences Research Branch (BSSRB) organized an expert-consultation meeting focused on both the challenges of tailoring behavioral and social interventions for specific individuals and targeting these interventions for specific communities. The meeting took place August 2-3 in Bethesda, MD. Experts from within and outside of oral health were invited to discuss the state-of-the-science of current tailoring and targeting practices and to provide recommendations about future directions for behavioral and social intervention research. A meeting summary will be available shortly on the NIDCR web site. Recommendations provided by the expert-consultants will be considered during the development of future BSSRB proposed initiatives.
National Cancer Institute (NCI) Translational Science Meeting
Staff participated in the NCI Translational Science Meeting held in Washington, D.C., in July. The purpose of the meeting was to encourage the use of “omics” technology to improve cancer therapy, encourage novel approaches for translational research, increase collaboration among cancer investigators, and provide a venue for investigators, clinicians, NIH staff, and stakeholders to interact. In addition to meeting with NIDCR grantees, NIDCR staff also met with NCI program staff and discussed the Specialized Programs of Research Excellence (SPORE) in Head and Neck Cancer, currently co-funded by NIDCR.
Society of Behavioral Medicine Meeting
Staff attended the annual meeting of the Society of Behavioral Medicine (SBM), held April 27-30 in Washington, D.C. Behavioral medicine is an interdisciplinary science focused on integrating knowledge about biological, behavioral, and social sciences as they relate to health and illness. Staff members are collaborating with the SBM planning committee and oral health researchers to ensure that oral health research is highlighted at the upcoming SBM conference that will be held April 2012 in New Orleans. The theme of the 2012 conference is establishing new collaborations between behavioral medicine and experts from other scientific disciplines and scientific organizations to tackle clinical problems of common interest. The SBM planning committee views the oral health research community as a valuable new community for collaboration and hopes to begin building partnerships at their 2012 conference.
Association for Psychological Science
Staff attended the annual conference of the Association for Psychological Science held in May in Washington, D.C., and participated in a grant writing workshop for early career investigators. Staff also discussed NIDCR’s possible participation in the May 2012 conference to be held in Chicago, in particular continuing to encourage use of the NIDCR-supported supplemental issue of the Journal of Public Health Dentistry (JPHD) as a resource in behavioral and social intervention research. As a result, the NIDCR has been invited to organize a special session at the 2012 conference to help disseminate the tools provided in the JPHD supplemental issue more widely. Further details about that special session will be announced in the Fall of 2011.
Other Meetings Attended by NIDCR Staff:
- The HIV/AIDS Strategic Working Group Meeting organized by the National Institute of Allergy and Infectious Diseases (NIAID) and the Office of the Director/Office of AIDS Research, held May 11 in Rockville, MD.
- Workshop on “Opportunities in Translational Science Research: Enabling New Research for Patient-Centered Outcomes Research, Comparative Effectiveness Research, Health Economics and Applied Informatics,” an Air Force Medical Service-Clinical and Translational Science Awards (AFMS-CTSA) Collaboration, held May 13 in Bethesda, MD.
- Workshop on “Defining Innate Immune Responses through Functional Genomics,” hosted by NIAID on June 8 in Bethesda, MD.
- The Eighth International Enamel Conference (Enamel VIII), held June 8-12 in Utica, IL. NIDCR co-funded this conference.
- The 9th Annual Meeting of the International Society for Stem Cell Research, held June 15-18 in Toronto, Canada.
- The AIDS Clinical Trials Group-Oral HIV/AIDS Research Alliance (ACTG-OHARA) Annual Scientific Meeting, held June 20-24 in Washington, DC.
- NCI Professional Development Workshop and Cancer Health Disparities 2011 Program Meeting, held July 12- 14 in Bethesda, MD, sponsored by the NCI Center to Reduce Cancer Health Disparities.
- Gordon Research Conference on “Periodontal Diseases: 30 Years of Progress,” held July 17-22 in Davidson, NC. NIDCR funded this conference.
- American Sociological Association Meeting, held in August in Las Vegas, NV.
Staff attended to represent NIDCR’s involvement in the trans-NIH initiative on basic behavioral and social sciences research, referred to as the Opportunity Network, or “OppNet.”
- Frontiers in Basic Cancer Research Conference, organized by the American Association for Cancer Research (AACR), held September 14-18 in San Francisco, CA.
- The American Society for Bone and Mineral Research, held September 16-20 in San Diego, CA.
- Gordon Research Conference on Human Genetics & Genomics, held July 17-22 in Newport, RI.
- Structural Birth Defects meeting, held August 10.
Science Updates and Interviews with Oral Health Researchers
Since the last meeting of the NADCRC, NIDCR communications staff produced a number of "Science News in Brief" summaries of recent research findings. Topics included: A comprehensive analysis of microbiota in the mouths of caries-free and caries-rampant kids; dentin matrix protein-1 (DMP1) may have amphibian origins; microparticles within the immune system can be bioengineered to better resolve inflammation; the anaerobic bacterium P. gingivalis can be genetically engineered to express a green fluorescent protein probe; and researchers are close to crystallizing a key protein in the bacterium T. denticola.
Exhibits and Interviews with Exhibit Visitors
Over the past few months, NIDCR exhibited and distributed patient and health professional education materials at the following meetings:
Pacific Northwest Dental Conference in Seattle, WA, June 16-18
American Dental Hygienists’ Association annual session in Nashville, TN, June 17-18
National Dental Association (NDA) annual convention in Baltimore, MD, July 22-26
Staff also interviewed visitors to the NIDCR booth during the July NDA meeting. Attendees were asked about their familiarity with the Institute and its consumer and health professional publications. Interviewees also answered questions about oral health topics they’d like to see materials on, and about the preferred formats for oral health information (e.g., print, audiovisual, via social media, etc.). Similar interviews have been conducted at other exhibits/meetings and will be conducted at selected upcoming conferences. Information gathered from these interviews helps inform the development of new health and science education materials, the formats that might be most helpful to NIDCR audiences, and whether more marketing/outreach is needed in cases where audience members are not aware of NIDCR or its health education materials.
New Science of Tooth Decay Publication Under Development
Institute communications staff are developing a new publication titled “The Tooth Decay Process: How to Reverse It and Avoid a Cavity.” The publication aims to explain the tooth decay process to parents and intermediaries. Feedback on a draft of the publication was collected from participants at the National Head Start Association annual conference in Kansas City, MO. Overall, the draft publication was very well received by the Head Start directors, teachers, health services staff, and parents who reviewed it. Next steps are to address changes/additions suggested by conference attendees, including the need for a new illustration to demonstrate the remineralization-demineralization process, a PowerPoint version of the publication to be used for parent and teacher trainings, a video for audiences with limited literacy skills, and development and testing of a Spanish-language version. Additional feedback will be collected via an online survey when the publication is posted on the NIDCR website.
Planning Underway for Fall Workshop on Urban Indians
Each year NIDCR staff, as part of the NIH Trans-NIH American Indian and Alaska Native Health Communications workgroup, help plan a workshop to guide NIH communications staff in their efforts to develop culturally appropriate health information for Native communities. This year’s workshop will take place on November 16 on the NIH campus. The focus will be on urban Indians, who make up more than half of the American Indian population in the United States. The keynote speaker will be Mr. D'Shane Barnett, Executive Director of the National Council of Urban Indian Health. Dr. Kristen Nadeau with the NIDCR-funded Center for Native Oral Health Research will also speak at the event about her work on type 2 diabetes in American Indian youth, as well has her current project looking at oral health issues in urban Indian teens.
Trans-NIH Blueprint for Neuroscience Grand Challenge on Pain Initiative
DER staff continue to head the trans-NIH Blueprint for Neuroscience Grand Challenge on Pain Initiative. The Blueprint re-issued the RFA: NIH Blueprint for Neuroscience Research Grand Challenge on the Transition from Acute to Chronic Neuropathic Pain (R01): http://grants.nih.gov/grants/guide/rfa-files/RFA-DE-12-008.html. The receipt date is October 4, 2011.
New Requests for Applications
Basic Research on Decision-Making: Cognitive, Affective, and Developmental Perspectives (R01):
Sleep and Social Environment: Basic Biopsychosocial Processes (R21):
Effectiveness of Treatment for Oral Diseases in Medically Compromised Patients (R01):
Effectiveness of Treatment for Oral Diseases in Medically Compromised Patients (R21):
Collaborative Research on the Transition from Acute to Chronic Pain: New Models and Measures in Clinical and Preclinical Pain Research (R01):
Economic Research on Incentives for Efficient Use of Preventive Services (R01):
Functional Restoration of Salivary Glands (R01):
Functional Restoration of Salivary Glands (R21):
New Program Announcements
Building a Genetic and Genomic Knowledge Base in Dental, Oral, and Craniofacial Diseases and Disorders (R01):
NIDCR Institutional Career Development Award for Enhancing Research Capacity in Temporomandibular Joint Disorders and Orofacial Pain (K12):
Systems Science and Health in the Behavioral and Social Sciences (R01):
Systems Science and Health in the Behavioral and Social Sciences (R21):
Systems Developmental Biology for Understanding Embryonic Development and the Ontogeny of Structural Birth Defects (R01):
Immunopathogenesis of HIV/AIDS-related Oral Manifestations and Host Immunity (R01):
Immunopathogenesis of HIV/AIDS-related Oral Manifestations and Host Immunity (R21):
NIH Exploratory/Development Research Grant Program (Parent R21):
Research Project Grant (Parent R01):
Research Resource for Discovering New Salivary Gland Gene Functions
Oral tissues form during embryonic development under the control of precisely choreographed patterns of gene expression. Functionally important changes in gene regulation can occur rapidly and locally within each tissue. Consequently, a microanatomical atlas of gene expression for each tissue during early development should provide new insights into tissue and organ formation.
NIDCR scientists have now mapped the changing patterns of gene expression in the developing submandibular salivary glands of the mouse. Their new microanatomical atlas reveals dramatic changes in the expression of hundreds of specific genes at local tissue sites as they establish the distinctive branched architecture of salivary glands. Major differences in gene expression were identified in histologically indistinguishable cells separated by small distances. This work also provides bioinformatic analyses of the changing patterns of gene expression. The data for individual genes and classes of genes (and other types of salivary gland gene expression data) are available on the NIDCR website at: http://sgmap.nidcr.nih.gov/sgmap/sgexp.html
This type of database can be used to discover new genes that regulate tissue formation. For example, the researchers used their atlas to find that loss of GSK-3β gene expression was causally associated with the development of new clefts.
An in-depth understanding of how normal glands are created promises to provide new approaches to facilitate gland regeneration and to engineer artificial salivary glands. The research was conducted in NIDCR’s Laboratory of Cell and Developmental Biology, in collaboration with the Developmental Mechanisms Section, and was published in the Journal of Dental Research. The scientists who conducted the research were Musselmann K, Green JA, Sone K, Hsu JC, Bothwell IR, Johnson SA, Harunaga JS, Wei Z, and Yamada KM.
Researchers Close to Crystallizing a Key Protein in T. Denticola
T. denticola is a member of the so-called red microbial complex, a triad of oral pathogens that are strongly associated with the most severe and chronic forms of periodontitis. Studies show that T. denticola normally comprises less than 1 percent of the mouth’s total bacterial load. But in periodontal pockets, the bacterium can exceed 40 percent of the microbial population.
In the June issue of the journal Acta Crystallographica Section F Structural Biology Crystallography Communications, NIDCR grantees and colleagues have placed T. denticola under the microscope again, obtaining recombinant crystals to begin the process of solving the three-dimensional crystal structure of its FhbB protein. The 11.4 kDa, 102-amino-acid surface protein plays a critical role in helping the bacterium survive in gingival crevices and periodontal pockets. How, the authors explain, requires a little background. The human body produces approximately 30 different proteins that are collectively referred to as complement. Complement recognizes pathogens and tags them for killing by other components of the innate immune system. However, too much complement activity can damage our own cells. To solve this problem, the innate immune system relies on several proteins—including the glycoprotein Factor H – to negatively regulate complement activity.
Mounted on the bacterium’s surface like a biochemical magnet, the FhbB protein of T. denticola attracts circulating Factor H and exploits its negative regulatory ability as biochemical cover to evade the complement system. This allows T. denticola to survive and thrive in periodontal pockets. Interestingly, FhbB is the smallest known bacterial protein that binds Factor H. With its crystal structure in hand, the authors say they can begin to parse the protein to define the minimum molecular requirements, or signature, required to bind Factor H. This fundamental information will facilitate the development of therapeutic and preventive approaches for periodontal disease and other important infectious diseases. In addition, the study of the FH-FhbB interaction will also provide unique insight into several inheritable diseases that are attributed to aberrant factor H activity, including age related macular degenerative disease and atypical hemolytic uremic syndrome. Collaborating on this study were Miller DP, McDowell JV, Bell JK, and Marconi RT at Virginia Commonwealth University in Richmond, VA.
P. Gingivalis Genetically Engineered to Express a Green Fluorescent Protein Probe
By the early 2000s, use of Green Fluoresent Protein (GFP)—primarily found in the Pacific jellyfish, Aequoria Victoria—had become a must have to visualize a variety of cellular processes with breathtaking, glow-in-the-dark clarity. But among microbiologists, there was a rub. The GFP protein and its variants required oxygen to work their magic, and that limited greatly their applicability to anaerobic, or oxygen-phobic microorganisms. For scientists who study the oral biofilm, that can be a big problem. Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium spp., Peptostreptococcus, Eubacterium – all are anaerobic, and all are associated with chronic periodontitis. Following these bugs and their metabolic activities in real-time would provide a much-needed tool to track the onset and progression of chronic periodontitis.
In the April issue of the journal PLoS ONE, a team of NIDCR-supported scientists reports that it has the solution. They demonstrated for the first time in P. gingivalis that a strictly anaerobic microorganism can be genetically engineered to express a green fluorescent protein probe. In this case, the probe is an adaptation of the recently discovered oxygen-independent flavin mononucleotide (FMN) fluorescent proteins. Their natural fluorescence derives not from jellyfish, the original source of GFP, but from blue light-sensing proteins of the bacteria Bacillus subtilis and Pseudomonas putida.
In their initial in vitro experiments, the scientists could directly track green protein-expressing P. gingivalis as it invaded living human gingival epithelial cells. The scientists could distinguish in which cellular compartments copies of the bacterium colocalized, a microscopy term for an overlap of fluorescent tags that would indicate their close spatial proximity. The researchers also found the bioengineered bacteria were equally adept as natural P. gingivalis at invading the gingival cells and proliferating within them. Based on their initial work, the scientists said they are confident the technique will be effective in additional cell types and to track the movement of P. gingivalis and other anaerobes in animal models.
Collaborating on the study were Choi CH, DeGuzman JV, Lamont RJ, and Yilmaz Ö at the University of Florida in Gainesville, FL.
Immune System Microparticles Can be Bioengineered to Better Resolve Inflammation
In the May 15 issue of The Journal of Immunology: Cutting Edge section, NIDCR grantees and colleagues report an important new find. They show that microparticles derived from circulating white blood cells called polymorphonuclear (PMN) leukocyte cells taken from inflammatory exudates contain specialized, pro-resolution lipid mediators that help to halt acute inflammation. The implication being, the microparticles deliver the lipid mediators to signal the inflammatory sites to promote resolution.
The finding raised an intriguing possibility. If PMN-derived microparticles are inherently anti-inflammatory and can signal resolution, as their data showed, could these vesicles be employed like Trojan horses to construct and deliver other bioengineered, pro-resolution nanoparticles? If so, the approach would further enhance the resolution phase and mimic the body’s own novel healing mechanisms. But because the microparticles are natural occupants of the circulatory system, they would deliver their payload without triggering the toxic side effects that many man-made biomaterials now prompt.
To test the idea, the researchers harnessed microparticles from human PMNs and used them to construct nanoparticles that they enriched with either aspirin-triggered resolvin D1 or a lipoxin A4 analog, both well established pro-resolution lipid mediators. They then administered their novel nanomedicines intravenously to mice with experimentally induced inflammation of a temporomandibular joint (TMJ). In their proof-of-principle study, the scientists found that a dose of just 10 nanograms of microparticle-bearing resolvin D1 and the lipoxin A4 analog protected against TMJ inflammation.
Investigators on the study were Norling LV, Spite M, Yang R, Flower RJ, Perretti M, and Serhan CN at the Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School.
Dentin Matrix Protein-1 May Have Amphibian Origins
In oral biology, one of the most fascinating unfolding genomic stories involves dentin matrix protein-1 (DMP1) and dentin sialophosphoprotein (DSPP). Both belong to a currently five-member family of non-collagenous, extracellular proteins called SIBLINGs, short for “small integrin-binding ligand, N-linked glycoprotein.” These proteins seem to play an important role in regulating the mineralization of collagen fibers that, in turn, results in the production of bone and dentin.
In the late 1990s, researchers discovered that the SIBLING genes, including DMP1 and DSPP, are clustered on human chromosome four, which suggests a possible shared evolution. When researchers looked deeper into the structure of the SIBLING gene sequences, they noticed a profoundly interesting possibility. The patterns written into the sequence indicated that the SIBLINGs likely were the products of an ancient gene duplication, from which each gene followed its own evolutionarily divergent path to its functional present.
An NIDCR intramural scientist and a post doc have tracked this genomic story with a strong focus on DMP-1 and DSPP. The NIDCR scientist now moves the story forward with an intriguing possibility. As published online on May 9 in the journal Cells Tissues Organs, he proposes that an ancient, amphibian-like DMP1 gene was duplicated in a common ancestor of reptiles and mammals. The duplicated gene, consisting of simple tandem repeat DNA sequences, permanently integrated on one end of the SIBLING gene cluster. That led to at least two evolutionarily divergent outcomes: one, reptiles began using the portion of the duplicated DMP1-like gene that geographically flanks a gene called SPARCL1. The reptiles then transcribed the sequence near SPARCL1 and produced a new protein, the function of which is undetermined; two, the entire mammalian lineage, which includes humans, transcribed the opposite end of the duplicated DMP-1 gene, away from SPARCL1 and flanking another gene called IBSP. This alternate site of replication, in turn, produced a protein that evolved separately into a DSPP-like protein, a precursor of today’s DSPP in human dentin.
“Both classes of animals [reptile and mammal] retained their second copy of the DMP1 gene presumably to continue the original functions of this more ancient SIBLING gene product,” the author explained. The scientist noted that research on the evolutionary origins of SIBLING proteins will be critical in determining their precise roles in bone and dentin formation and in learning to mimic their structure and function to better regenerate these tissues in disease. The author of the study is Fisher LW from the NIDCR Craniofacial and Skeletal Diseases Branch, Matrix Biochemistry Section.
Comprehensive Analysis of Microbiota in Mouths of Caries-free and Caries-Rampant Children
How do the microbes, or microbiota, in the mouths of caries-free and caries-rampant kids differ? A team of NIDCR-supported researchers recently published its two-part answer to this question, using a combination of molecular and cell-culture approaches that it backstopped by the bioinformatics of the Human Oral Microbiome Database (HOMD). The latter is a free online encyclopedic repository of collated biological information on more than 600 oral microbes.
In the first paper, published in September 2010 on the Caries Research website, the scientists found significant differences in the microbiota of 80 preschool children, about half with severe childhood caries and the rest without decay. Their data were based specifically on the cloning and amplification of microbial DNA from plaque samples. This approach indicated that Granulicatella elegans and species within Bifodobacteriaceae seem to be caries-associated pathogens. So were Neisseria, Veillonella, and some other caries-associated species that do not produce enamel-dissolving acids. The latter finding suggests these bacteria may have a possible symbiotic or otherwise supportive role in the caries process.
Interestingly, based on their clonal analysis, the scientists found S. mutans was present infrequently in both groups of children. However, using PCR assays designed specifically for S. mutans, the bacterium was significantly associated with severe early childhood caries. They speculated that the discrepancy might be due to the greater sensitivity of PCR assays to pick out low-frequency species, such as S. mutans.
“These data are thus consistent with the observation that carious sites may harbor widely diverse bacteria, and S. mutans, while important in disease, may be present only in low proportions at carious sites,” the authors noted.
In the second paper, published in the April 2011 issue of the Journal of Clinical Microbiology, the scientists upped the investigational ante. Previous studies on the subject had identified microbes of interest primarily based on phenotype, meaning observable physical or biochemical manifestations. But looks can be deceiving. To cast a more comprehensive and informative research net, the scientists started with specially designed, more labor-intensive techniques to grow anaerobic bacteria, the predominant microbes in the oral biofilm and which can be notoriously difficult to culture. They then employed molecular techniques to pull out signature DNA sequences from the microbes that they could reference in the HOMD database.
Using this multi-pronged strategy, the scientists compared differences in the microbiota of 82 preschool children, about half with severe childhood caries and the rest without decay. They again found significant differences in the two groups. The two major bacterial species associated with decay were S.mutans and a recently named organism called Scardovia wiggsiae. Intriguingly, S. wiggsiae was associated with severe childhood caries in preschoolers without S. mutans. Previous studies suggested S. wiggsiae might play a role in childhood caries, and the organism now becomes a candidate for further study.
The first study was carried out by Kanasi E, Dewhirst FE, Chalmers NI, Kent R Jr, Moore A, Hughes CV, Pradhan N, Loo CY, and Tanner AC at The Forsyth Institute in Boston, MA. Collaborators on the second study were Tanner AC, Mathney JM, Kent RL, Chalmers NI, Hughes CV, Loo CY, Pradhan N, Kanasi E, Hwang J, Dahlan MA, Papadopolou E, and Dewhirst FE, also at Forsyth.
Dr. Sundaresan Venkatachalam Appointed Director of Epithelial Cell Regulation and Transformation Program
Dr. Sundaresan Venkatachalam joined the NIDCR in June as director of the Epithelial Cell Regulation and Transformation Program in the DER Integrative Biology and Infectious Diseases Branch. Prior to joining the NIDCR, Dr. Venkatachalam was assistant professor in the Department of Biochemistry, Cellular and Molecular Biology at the University of Tennessee, Knoxville, where he conducted NIH-supported research on the role of chromatin remodeling proteins, transcription factors and epigenetic mechanisms in DNA damage responses and tumor suppression, and the development of in vivo and in vitro test systems for genetic toxicology and carcinogenesis. He also was a faculty member of the Genome Science and Technology Program and course director of undergraduate and graduate level cancer biology. Dr. Venkatachalam earned his Ph.D. in biochemistry from the Ohio State University and received postdoctoral training at the Baylor College of Medicine. At the NIDCR, he will manage a portfolio of grants and cooperative agreements in basic and translational research on the molecular mechanisms of oral epithelial cell regulation as they relate to the onset and progression of diseases of the oral mucosa, head and neck cancers (including oral/oropharyngeal), and salivary gland cancers.
Dr. Dena Fischer Joins Center for Clinical Research
In August, Dr. Dena Fischer joined the DER Center for Clinical Research as a program officer. She previously was a faculty member at the University of Illinois at Chicago College of Dentistry for the past five years. Dr. Fischer received her dental degree from the University of Michigan in 1998 and then completed a two-year general practice residency at the University of North Carolina Hospitals. Her residency was followed by four years of training in oral medicine at the University of Washington. During this time, she also earned a master’s degree in epidemiology. Since graduating from dental school, Dr. Fischer has provided oral health care to medically complex patients, patients with HIV-infection, TMJD patients, adult patients with severe disabilities, and patients with dysplastic oral lesions. Her past research includes studies of the reliability of histopathologic diagnosis of oral pre-malignant and malignant lesions, studies of oral pain, and oral health issues at the end of life.
Dr. Lauren Davidson Named New Animal Program Director
Lieutenant Commander Lauren Davidson is DIR’s new Animal Program Director. Dr. Davidson completed a laboratory animal medicine residency at NIH and comes to the NIDCR with about five years experience as a senior staff laboratory animal veterinarian at NICHD. She also previously worked as a veterinary officer at the Uniformed Services University of the Health Sciences (UHSUS) and at the Food and Drug Administration. Dr. Davidson received her D.V.M. from University of Florida College of Veterinary Medicine. She obtained a master’s of comparative medicine at UHSUS and holds a small animal clinical internship certificate, with one year of postdoctoral internship in small animal medicine and surgery. Her primary interest in laboratory medicine is with rodents; she also has a broad range of expertise, including working with primates and as a practicing small animal veterinarian.
Dr. Ken Yamada Named NIH Distinguished Investigator
Dr. Ken Yamada, chief of the Laboratory of Cell and Developmental Biology, was selected by NIH for promotion to NIH Distinguished Investigator.
The title of Distinguished Investigator is reserved for NIH tenured intramural senior investigators who are at the very highest level of career accomplishments in their respective fields. This promotion is an acknowledgement by NIH of his significant contributions and scientific achievements to date and made in anticipation of his future novel research advances.
IETP Fellow is Winner of Endocrine Society Poster Competition
Alison Boyce, M.D., an Inter-institute Endocrine Training Program (IETP) fellow working in the Skeletal Clinical Studies Unit, DIR Craniofacial and Skeletal Diseases Branch, was the winner of the Presidential Poster Competition at the 2011 Meeting of the Endocrine Society. Her abstract was entitled, “A novel syndrome of neurocutaneous melanosis, FGF23-mediated hypophosphatemia, and a mosaic skeletal dysplasia.”
Dr. Pamela Robey Appointed Journal Editor
Pamela Gehron Robey, Ph.D., chief of the DIR Craniofacial and Skeletal Diseases Branch, was recently appointed as an associate editor of the journal Stem Cell Research.
Division of Intramural Research
Alevizos I, Alexander S, Turner JT, Illei GG. MicroRNA expression profiles as biomarkers of minor salivary gland inflammation and dysfunction in Sjögren’s syndrome. Arthritis and Rheumatism 63:535-44, 2011
Ambudkar IS. TRPV4 mediates tumor-derived endothelial cell migration via arachidonic acid-activated actin remodeling. Oncogene. 2011 Jun 20. doi: 10.1038/onc.2011.231. [Epub ahead of print] PMID: 21685934
Fiorio Pla A, Ong HL, Cheng KT, Brossa A, Bussolati B, Lockwich T, Paria B, Munaron L, Greenwell-Wild T, Moutsopoulos NM, Gliozzi M, Kapsogeorgou E, Rangel Z, Munson PJ, Moutsopoulos HM, Wahl SM. Chitinases in salivary glands and circulation in Sjögren's syndrome - macrophage harbingers of disease severity. Arthritis Rheum. 2011 May 25. [Epub ahead of print]
Ishikawa I, Iwamoto T, Nakamura T, Doyle A, Fukumoto S, and Yamada Y. Pannexin 3 functions as an ER Ca2+ channel, hemichannel, and gap junction to promote osteoblast differentiation. J Cell Biol 193:1257-74, 2011
Kondratowicz AS, Lennemann NJ, Sinn PL, Davey RA, Hunt CL, Moller-Tank S, Meyerholz DK, Rennert P, Mullins RF, Brindley M, Sandersfeld LM, Quinn K, Weller M, McCray PB Jr, Chiorini J, Maury W. T-cell immunoglobulin and mucin domain 1 (TIM-1) is a receptor for Zaire Ebolavirus and Lake Victoria Marburgvirus. Proc Natl Acad Sci U S A. May 17;108(20):8426-31. 2011
Martin D, Galisteo R, Molinolo AA, Wetzker R, Hirsch E, and Gutkind JS. PI3Kγ mediates kaposi's sarcoma-associated herpesvirus vGPCR-induced sarcomagenesis. Cancer Cell. 19:805-813, 2011.
Masedunskas A, Sramkova M, Parente L, Sales KU, Amornphimoltham P, Bugge TH, and Weigert R. Role for the actomyosin complex in regulated exocytosis revealed by intravital microscopy. Proc Natl Acad Sci U S A. 108: 13552-13557, 2011
Musselmann K, Green JA, Sone K, Hsu JC, Bothwell IR, Johnson SA, Harunaga JS, Wei Z, Yamada KM. Salivary gland gene expression atlas identifies a new regulator of branching morphogenesis. J Dent Res 90(9):1078-84, 2011
Sakurai A, Jian X, Lee CJ, Manavski Y, Chavakis E, Donaldson J, Randazzo PA, and Gutkind JS. PIP5 kinase and GEP100/Brag2 mediate antiangiogenic signaling by semaphorin3E-Plexin-D1 through Arf6. J Biol Chem. 2011 [Epub ahead of print]
Schafer JM, Peters DE, Morley T, Liu S, Molinolo AA, Leppla SH, and Bugge TH. Efficient targeting of head and neck squamous cell carcinoma by systemic administration of a dual uPA and MMP-activated engineered anthrax toxin. PLoS One. 6:e20532, 2011.
Szabo R, Rasmussen AL, Moyer AB, Kosa P, Schafer JM, Molinolo AA, Gutkind JS, and Bugge TH. c-Met-induced epithelial carcinogenesis is initiated by the serine protease matriptase. Oncogene. 30:2003-2016, 2011
Utreras E, Terse A, Keller J, Iadarola M, and Kulkarni AB. Resveratrol inhibits Cdk5 activity through regulation of p35 expression. Mol Pain 7(1):49, 2011
Wei, Z, Angerer, RC, Angerer, LM (2011) Direct development of neurons within foregut endoderm of sea urchin embryos. Proc. Nat. Acad. Sci USA, 108:9143-9147, 2011.
Wen J, Nikitakis NG, Chaisuparat R, Greenwell-Wild T, Gliozzi M, Jin W, Adli A, Moutsopoulos N, Wu T, Warburton G, Wahl SM. Secretory leukocyte protease inhibitor (SLPI) expression and tumor invasion in oral squamous cell carcinoma. Am J Pathol. 178(6):2866-78, 2011
Zheng C, Cotrim AP, Rowzee A, Swaim W, Sowers A, Mitchell JB, Baum BJ. Prevention of radiation induced salivary hypofunction following hKGF gene delivery to murine submandibular glands. Clin Cancer Res 17:2842-2851, 2011.
Zheng C, Voutetakis A, Goldstein B, Afione S, Rivera VM, Clackson T, Wenk ML, Boyle M, Nyska A, Chiorini JA, Vallant M, Irwin R, Baum BJ. Assessment of the safety and biodistribution of a regulated AAV2 gene transfer vector after delivery to murine submandibular glands. Toxicol Sci. May 30. 2011 [Epub ahead of print]
Szabo R and Bugge TH. Membrane-Anchored Serine Proteases in Vertebrate Cell and Developmental Biology. Annu Rev Cell Dev Biol. 2010 [Epub ahead of print].
Harunaga J, Hsu JC, Yamada KM. Dynamics of salivary gland morphogenesis. J Dent Res 90(9):1070-7, 2011
Mezey E. The therapeutic potential of bone marrow derived stromal cells. J Cell Biochem. 2011 June 15 [Epub ahead of print].
Chen W. Tregs in immunotherapy: opportunities and challenges. Immunotherapy. 2011 Aug;3(8):911-4.
Maruyama T, Konkel JE, Zamarron BF, Chen W. The molecular mechanisms of Foxp3 gene regulation. Semin Immunol. 2011 Jul 11. [Epub ahead of print]
Recent publications from K awardees:
Chen IP, Wang L, Jiang X, Aguila HL, Reichenberger EJ. Phe377del mutation in ANK leads to impaired osteoblastogenesis and osteoclastogenesis in a mouse model for craniometaphyseal dysplasia (CMD). Hum Mol Genet. 2011 Mar 1;20(5):948-61. PMCID: PMC3033186
Chi DL, Momany ET, Jones MP, Damiano PC. Timing of first dental visits for newly Medicaid-enrolled children with an intellectual or developmental disability in Iowa, 2005-2007. Am J Public Health. 2011 May;101(5):922-9. PMCID: PMC3076421
Dos Santos PH, Karol S, Bedran-Russo AK. Long-term nano-mechanical properties of biomodified dentin-resin interface components. Biomech. 2011 Jun 3;44(9):1691-4. PMCID: PMC3111941
Gule MK, Chen Y, Sano D, Frederick MJ, Zhou G, Zhao M, Milas ZL, Galer CE, Henderson YC, Jasser SA, Schwartz DL, Bankson JA, Myers JN, Lai SY. Targeted therapy of VEGFR2 and EGFR significantly inhibits growth of anaplastic thyroid cancer in an orthotopic murine model. Clin Cancer Res. 2011 Apr 15;17(8):2281-91. PMCID: PMC3079006
Ioannidou E, Swede H. Disparities in periodontitis prevalence among chronic kidney disease patients. J Dent Res. 2011 Jun;90(6):730-4. PMCID: PMC3092844
Jiffar T, Yilmaz T, Lee J, Hanna E, El-Naggar A, Yu D, Myers JN, Kupferman ME. KiSS1 mediates platinum sensitivity and metastasis suppression in head and neck squamous cell carcinoma. Oncogene. 2011 Jul 14;30(28):3163-73. PMCID: PMC3136629
Karthikeyan R, Amaechi BT, Rawls HR, Lee VA. Antimicrobial activity of nanoemulsion on cariogenic Streptococcus mutans. Arch Oral Biol. 2011 May;56(5):437-45. PMCID: PMC3064956
Kim, RH; Lee, R S; Williams, D; Bae, S; Woo, J; Lieberman, M; Oh, J-E; Dong, Q; Shin, KH; Kang, MK; Park, NH. Bisphosphonates induce senescence in normal human oral keratinocytes. J Dent Res 2011 Jun; 90(6), 810-6. PMCID: PMC3144120
Kopycka-Kedzierawski DT, Billings RJ. Prevalence of dental caries and dental care utilisation in preschool urban children enrolled in a comparative-effectiveness study. Eur Arch Paediatr Dent. 2011 Jun;12(3):133-8. PMCID: PMC3111947
Tseng ZJ, McNitt-Gray JL, Flashner H, Wang X, Enciso R. Model sensitivity and use of the comparative finite element method in mammalian jaw mechanics: mandible performance in the gray wolf. PLoS One. 2011 Apr 29;6(4):e19171. PMCID: PMC3084775
Recent publications from F awardees:
Black KC, Liu Z, Messersmith PB. Catechol Redox Induced Formation of Metal Core-Polymer Shell Nanoparticles. Chem Mater. 2011 Mar 8;23(5):1130-1135. PMCID: PMC3109993
Niu K, Saloman JL, Zhang Y, Ro JY. Sex differences in the contribution of ATP-sensitive K+ channels in trigeminal ganglia under an acute muscle pain condition. Neuroscience. 2011 Apr 28;180:344-52. PMCID: PMC3124308
Scanlon CS, Marchesan JT, Soehren S, Matsuo M, Kapila YL. Capturing the Regenerative Potential of Periodontal Ligament Fibroblasts. J Stem Cells Regen Med. 2011 Jan 1;7(1):54-56. PMCID: PMC3129699
Schwend T, Loucks EJ, Snyder D, Ahlgren SC. Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in zebrafish. J Lipid Res. 2011 Jul;52(7):1328-44. PMCID: PMC3122913
Van Tubergen E, Vander Broek R, Lee J, Wolf G, Carey T, Bradford C, Prince M, Kirkwood KL, D'Silva NJ. Tristetraprolin regulates interleukin-6, which is correlated with tumor progression in patients with head and neck squamous cell carcinoma. Cancer. 2011 Jun 15;117(12):2677-89. PMID: 21656745