DEPARTMENT OF HEALTH AND HUMAN SERVICES
NATIONAL INSTITUTES OF HEALTH
Witness appearing before the
Senate Subcommittee on Labor-HHS-Education Appropriations
Lawrence A. Tabak, D.D.S., Ph.D.
National Institute of Dental and Craniofacial Research
June 22, 2007
Mr. Chairman and Members of the Committee:
I am pleased to present the President’s budget request for the
National Institute of Dental and Craniofacial Research (NIDCR) of the
National Institutes of Health (NIH). The Fiscal Year (FY) 2008 budget
request for NIDCR is $389,722,000.
FACING THE FUTURE: INTEGRATIVE APPROACHES TO ADVANCE PUBLIC HEALTH
Innovation has long been the great engine of progress in American
life, including the tremendous progress made in improving the Nation's
oral health over the last half century. From the tube of fluoridated
toothpaste in the medicine cabinet to the high-resolution digital X-ray
unit in the dentist's office, scientific innovations have helped more
people than ever keep their teeth for a lifetime.
The Nation's oral and craniofacial researchers stand on the
threshold of even greater innovations to improve the lives of millions
of Americans. No longer must they attempt to understand health and
disease one gene and protein at a time. Today, they can click the
computer mouse on their desks and call up vast databases of biological
information. In essence, thousands of pieces to the biological puzzle
are now on the table. If we meet the challenge to integrate the pieces
- intentionally blurring in the process the lines that have defined the
traditional research disciplines - great progress can be made in
understanding the molecular underpinnings of oral and craniofacial
health and disease. This year, I would like to offer a few of the many
examples of how integrative science will lead to greater innovation.
I’d also like to highlight how this innovation ultimately will lead to
more personalized dentistry and medicine in which treatment can be
tailored to a patient’s specific disease and healthcare needs.
CRANIOFACIAL CONSTRUCTION AND RECONSTRUCTION
The human face has been celebrated in art and literature since time
immemorial and rightfully so. It is among the body’s most distinctive
structures and, is also one of the most developmentally complex
structures of nature. Tremendous progress has been made in recent
years in unraveling the genetic programs that are activated in the
embryo to produce the face and the skull. Similar progress has been
made in pinpointing which genes can go awry to produce a cleft lip
and/or palate.
But much work remains. We must decipher the
developmental programs that give rise to the various craniofacial
tissues, hard and soft. By knowing how the craniofacial complex is
assembled, it will be possible to better reassemble tissues that are
damaged, either at birth or due to injury later in life. Exciting
research is under way to explore the viability of regenerating damaged
bone, teeth, and soft tissues with stem cells, novel biomaterials, and
growth-promoting proteins. NIDCR-supported researchers recently
reported success using stem cells to engineer a replacement
root/periodontal complex that could support a porcelain crown and
provide normal tooth function in studies with mini pigs. Other
investigators are well on the way to creating a replacement gum tissue
that can be produced in sufficient quantity to repair large oral
defects.
The developmental programs will be helpful not only in treating
craniofacial abnormalities but in preventing them. This year, for
example, a team of NIDCR grantees determined that women who smoke
during pregnancy and carry a fetus whose DNA lacks both copies of a
gene involved in detoxifying cigarette smoke substantially increase
their baby’s chances of being born with a cleft lip and/or palate.
About a quarter of babies of European ancestry and possibly up to 60
percent of those of Asian ancestry lack both copies of this gene. This
finding reinforces in a concrete, personal way the public health
message that women, especially those who are pregnant, should not
smoke.
HEAD AND NECK CANCER
The NIDCR also has made a major investment in promoting integrative
approaches to head and neck cancer. Our intent is to move beyond the
current imprecise clinical definitions of these tumors, which are
generally based on their appearance and patterns under a microscope.
We need to examine the genetic hard drives of these tumors’ cells to
understand their abnormal and often deadly behaviors. This work
already is taking place. NIDCR scientists have compiled comprehensive
profiles of proteins expressed in some head and neck cancers. This
information should help in developing true biomarkers with diagnostic
and prognostic value.
NIDCR-supported scientists are also developing new and exciting
visualization tools and approaches to improve diagnosis of oral
cancer. One such tool being tested is called the VELscope®. It is a
simple hand-held device that emits a cone of blue light into the mouth,
which excites various molecules within the tissue, causing the tissue
to absorb the light’s energy and re-emit it as visible fluorescence.
Because changes in the natural fluorescence of healthy tissue generally
are different from those indicative of developing tumor cells, the
VELscope® allows dentists to observe telltale differences.
In a recent follow-up study, the scientists reported that the
VELscope® performed extremely well in accurately and rapidly
delineating the real borders between tumor and healthy oral tissue
during biopsies in the clinic. Intriguingly, 19 of the 20 examined
tumors in the study had fluorescence changes that extended in at least
one direction beyond the clinically visible tumor. These extensions,
which are undetectable to the unaided eye and thus would likely not be
excised, extended up to an inch beyond the visible lesion. Leaving
these abnormal cells in the mouth increases the chance of other tumors
arising over time. The instrument was developed as one component of an
integrative approach to oral cancer detection and treatment that
combines cytology, molecular biology, and staining to improve early
detection. This finding and others will allow practitioners to gain a
better molecular characterization of developing tumors, providing the
intellectual basis for more personalized treatment and a future in
which fewer people will undergo disfiguring surgery to fight the
disease and/or die from these cancers.
SALIVARY DIAGNOSTICS
Other diagnostic tools are under development as well. The NIDCR is
a national leader in development of the use of saliva as a diagnostic
fluid. Several Institute grantees are working to develop tiny
automated machines, which can rapidly and precisely perform many
diagnostic functions that previously required painful needle sticks.
One group recently fabricated the first disposable, low-cost,
miniaturized diagnostic platform that can process small amounts of
saliva, amplify its DNA and detect the levels of genetic sequences of
interest. Work is proceeding to ultimately create a fully functional
hand-held instrument for everyday use to detect conditions ranging from
oral cancer to cardiovascular disease to AIDS.
TEMPOROMANDIBULAR MUSCLE AND JOINT DISORDERS
Integrative approaches are proving productive in our ongoing efforts
to understand temporomandibular muscle and joint disorders, or TMJDs.
Previously, NIDCR-supported scientists found that different sets of
common sequence variations in the COMT gene correlate with low,
moderate, and high susceptibility to chronic pain. This finding makes
good biological sense. The COMT gene encodes an enzyme that helps to
inactivate nerve signaling compounds and stop the transmission of an
unpleasant sensation. The scientists recently showed that each of
these sets of sequence variations changes the resulting structure of
the corresponding messenger RNA. When a gene is expressed, it is
copied into messenger RNA which, like an order form, contains the
information to produce a specific protein. The scientists determined
that the genetic variations that correlate with high sensitivity to
pain produce messenger RNA with long, rigid loops in their structure,
which reduces the rate of COMT protein synthesis and thus slows the
nerve’s ability to turn off an unpleasant sensory signal. The likely
result: those with the “sensitive” variations will personally
experience the sensation of pain longer and possibly more intensely.
Such
findings are particularly exciting because these studies could not have
been conducted just a generation ago. Not enough was known about the
basic mechanisms of pain. But as more of the biochemical pieces to the
puzzle are found in the years ahead, great progress in controlling pain
will be possible, and the NIDCR will help in leading the way for all
those battling chronic pain conditions, including TMJDs, to find relief
through a more accurate diagnosis and more personalized care.
DENTAL DISPARITIES: RIGOROUS SCIENCE, PRACTICAL RESULTS
It now has been seven years since the U. S. Surgeon General issued the report Oral Health in America.
As many will recall, that report pulled together for the first time the
stark statistics of the Nation’s “silent epidemic” of tooth decay and
other oral diseases among its minority and underserved populations.
The reasons for these disparities are complex, but two facts were
indisputable in the report: Many oral diseases are either preventable
or easily controlled, and new strategies are needed to ensure that all
Americans are aware of and ultimately benefit from the latest research
advances.
To meet this need, the Institute established five Centers for
Research to Reduce Oral Health Disparities in 2001. This approach
allows scientists to assemble multi-disciplinary research teams that
lend a greater wealth of expertise to understand and address the
complex elements underlying oral health disparities at the community
level. Building on the knowledge and evidence amassed by the initial
health disparities centers, the Institute has begun preparations to
re-compete its center grants with a specific public health aim. That
aim is to assemble a more seamless investigative team structure that
can take a well-defined clinical issue and with the participation of a
community-based population, test the effectiveness of promising
interventions on a wider scale. This approach holds considerable
promise to yield rigorous science, participatory research with those in
underserved communities, and a significant reduction in oral health
disparities.
PRACTICE-BASED RESEARCH NETWORKS
The Institute awarded grants in early 2005 that established three
regional practice-based research networks, or PBRNs. Their mission is
to create networks of practicing dentists and dental hygienists with
their patient populations to participate in clinical studies on a
variety of pressing everyday issues in oral healthcare. In 2006, the
PBRNs were enlisted to investigate an important emerging health issue.
Millions of Americans currently take a type of drug called
bisphosphonates, typically to ease cancer-related pain or to prevent
osteoporosis. But recent reports indicate that newly formulated
bisphosphonates can cause in some people a debilitating thinning of the
jawbone called osteonecrosis. What remains unclear is the prevalence
of this unwanted side effect and, more importantly, who precisely is at
risk. A few years ago, NIDCR would have lacked the clinical
infrastructure in place to investigate these and other related
questions. The PBRNs have changed the equation. The NIDCR has rapidly
organized the needed studies to investigate the problem and will
provide in the near future more meaningful data for the millions of
Americans at risk.
Traditional research approaches have
produced extraordinary benefits to the Nation’s public health. But we
now face a new scientific frontier, and new possibilities confront our
researchers. These opportunities require novel approaches that fall
under the rubric of integrative science. From this coordinated
approach to science, the biological complexity before us will give way
to simplicity and once unimaginable public health advances in which
personalized health and medicine become a reality.
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Biographical Sketch
NAME Lawrence A. Tabak
POSITION Director, National Institute of Dental and Craniofacial Research
BIRTHPLACE Brooklyn, New York
DATE December 15, 1951
EDUCATION B.S., Biology and Chemistry, City College of CUNY, 1972
D.D.S., Dentistry, Columbia University, 1977
Ph.D., Oral Biology, SUNY at Buffalo, 1981
Certificate of Proficiency in Endodontics, SUNY at Buffalo, 1985
EXPERIENCE
2000-present Director, National Institute of Dental and Craniofacial Research, NIH
2000-present Adjunct,
Senior (2006) Investigator, Section of Biological Chemistry National
Institute of Diabetes and Digestive and Kidney Diseases, NIH
2000 Adjunct Professor of Dentistry and of Biochemistry and
Biophysics, University of Rochester
1998-2000 Senior Associate Dean for Research, School of Medicine and
Dentistry, University of Rochester
1998-2000 Co-Director, Institutional Medical Scientist Training Program
(MSTP)
1998-2000 Professor of Dentistry and of Biochemistry and Biophysics
1998-2000 Director, Center for Oral Biology, Aab Institute of Biomedical
Sciences, University of Rochester
1996-2000 Director, Institutional Dentist Scientist Program
1996-1997 Professor, Dental Research and Biochemistry and Biophysics,
University of Rochester
1995-1997 Chair, Department of Dental Research, University of Rochester
1992-1996 Professor, Dental Research and Biochemistry, University of
Rochester
1988-1994 Director, Graduate Study, Department of Dental Research,
University of Rochester
1986-1992 Associate Professor, Dental Research and Biochemistry,
University of Rochester
1985-1986 Associate Professor, Endodontics and Oral Biology, SUNY/
Buffalo
1985-1986 Director, Graduate Study (Ph.D.), Oral Biology, SUNY/
Buffalo
1982-1983 Visiting Scientist, NIDR, Bethesda, MD
1981-1985 Assistant Professor, Endodontics and Oral Biology, SUNY/
Buffalo
1980-1981 Research Assistant Professor, Oral Biology, SUNY/Buffalo
HONORS AND AWARDS
2006 Honorary Doctorate, University of Medicine and Dentistry of NJ
2004 Named a Columbia University Alumnus “Ahead of the Times”
2002 Elected Member of the Institute of Medicine
1998 Elected Fellow of AAAS
1997-2000 USPHS MERIT Award (R37)
1997 Alumnus of the Year, School of Dental and Oral Surgery,
Columbia University
1996 IADR Distinguished Scientist Award – Salivary Research
1994 Manuel D. Goldman Prize for Excellence in First Year Teaching,
School of Medicine and Dentistry, University of Rochester
1994-1997 Dean’s Senior Teaching Fellow, School of Medicine and
Dentistry, University of Rochester
1993 Alumni Award for Excellence in Graduate Education, University
of Rochester
1991 Salivary Research Award (Salivary Research Group, IADR)
1987 IADR Young Investigator Award
1984-1989 USPHS Career Development Award (K04)
1984 Student Research Association Award (SUNYAB)