NATIONAL HEART, LUNG, AND BLOOD ADVISORY COUNCIL
MEETING MINUTES
May 26, 2010
I. CALL TO ORDER AND OPENING REMARKS -
Dr. Susan B. Shurin
Dr. Susan Shurin, Acting Director of the National Heart, Lung, and Blood
Institute (NHLBI), welcomed members to the 238th meeting of the National
Heart, Lung, and Blood Advisory Council (NHLBAC).
Council Updates:
Dr. Shurin welcomed four new Council members:
• Dr. Gary Gibbons, Director, Cardiovascular Research Institute,
Morehouse School of
Medicine (Atlanta, Georgia)
•Dr. Lanetta Jordan, Director, Sickle Cell Services, Memorial
Healthcare System (Miami, Florida)
• Dr. Talmadge King, Chair, Department of Medicine, University
of California (San Francisco, California)
• Dr. Leslee Shaw, Professor of Medicine, Emory University School
of Medicine (Atlanta, Georgia)
Staff Updates:
Dr. Shurin updated the Council on several leadership appointments:
• Dr. Harold Varmus — Director, National Cancer Institute
(NCI). Dr. Varmus, a former Director of the NIH and co-recipient of
the 1989 Nobel Prize in Physiology or Medicine for studies of the genetic
basis of cancer, is expected to assume his duties this summer after
Senate confirmation.
• Dr. Arun Chockalingam — Director, NHLBI Office of Global
Health
• Dr. Cristina Rabadan-Diehl — Deputy Director, NHLBI Office
of Global Health
• Ms. Susan Dambrauskas— Deputy Director, NHLBI Office
of Communications
The Search Committee for the new NHLBI Director is currently reviewing
applications (application deadline was April 30) and will send a list
of candidates to the Director, NIH, within a few months.
Invited Guests:
Dr. Shurin introduced Dr. George Daley, Professor of Hematology, Director
of the Stem Cell Transplantation Program (Howard Hughes Medical Institute/Children's
Hospital, Boston), and Professor of Biological Chemistry/Molecular Pharmacology
of Pediatrics at the Harvard Medical School.
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The Council was reminded that under Public Law 92-463, the Federal Advisory
Committee Act, a portion of the meeting would be closed to the public,
for the consideration of grant applications. Dr. Shurin also reminded
the Council members that they are Special Government Employees and are
subject to Departmental conduct regulations.
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Budget Update:
Dr. Shurin reviewed the Institute's FY 2011 President's Budget, which
totals $3,187,516,000, a 3.0 percent increase over FY 2010 (which approximates
the rate of inflation). The allocation between funding mechanisms is about
the same as in FY 2010. The Institute's ability to increase the success
rate for competing Research Project Grant (RPG) applications in FY 2011
is severely limited by its substantial commitment to noncompeting RPGs.
It is likely to be further limited because of the anticipated large increase
in the number of competing applications from the pool of unfunded applications
originally submitted in response to the American Recovery and Reinvestment
Act (ARRA).
The ARRA was signed into law by President Obama on February 17, 2009.
It provides $10.4 billion to the NIH (available for 2 years—through
September 2010) to support programs to stimulate the economy, create and
preserve jobs, and advance biomedical research.
The NHLBI's funding plan for its $763 million ARRA allocation strikes
a balance between increasing the number of investigator-initiated research
grants and supporting signature projects. The plan comprises participation
in NIH-wide ARRA initiatives ($372 million), expansion of the FY 2008
and FY 2009 NHLBI paylines ($292 million), participation in NIH-wide administrative
supplements ($91 million), and other support ($10 million).
Global Health:
Global health is receiving increased attention as worldwide patterns
of disease burden shift from acute infectious diseases to chronic diseases.
In March, 2010, the Institute of Medicine released a report entitled "Promoting
Cardiovascular Health in the Developing World: A Critical Challenge to
Achieve Global Health." A new era of global health research is unfolding.
In the global health arena, the NHLBI is guided by the following principles:
• Basic, clinical, and population-based research inform each
other.
• Priorities are always driven by the science.
• As more is learned about gene-environment interactions, we
need to bring observational and population-based studies closer to the
basic science.
• As global citizens, we learn from and partner with colleagues
throughout the world.
Major opportunities for the NHLBI in global health research lie primarily
in areas of chronic diseases (especially cardiovascular and pulmonary
disease and diabetes/obesity), genetic diseases (especially hemoglobinopathies
and bleeding and clotting disorders), and blood safety.
Dr. Shurin reviewed demographic and other data pertinent to the current
global disease burden and relevant research opportunities.
The network of 11 Collaborating Centers to help combat chronic diseases
in developing countries—a partnership between the NHLBI and UnitedHealth
Group—is an example of the Institute's global health activities.
Each Center includes a research institution in a developing country paired
with at least one partner academic institution in a developed country.
The Centers are developing infrastructures for research and training to
enhance their capacity to conduct population-based or clinical research
to monitor, prevent, or control chronic diseases, focusing on cardiovascular
and pulmonary diseases.
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Dr. Shurin summarized a recent Notice of Proposed Rule Making (published
in the Federal Register on May 21, 2010), which proposes changes to existing
regulations on the responsibility of applicants for promoting objectivity
in research for which Public Health Service (which includes the NIH) funding
is sought. The Proposal is open for public comment until July 20. See
NIH News Advisory (http://www.nih.gov/news/health/may2010/od-20.htm) for
more information.
Key elements of the Proposal include:
• Investigators and key personnel must disclose to their institutions
all financial interests (> $5,000) relevant to professional activities.
This removes the issue of Public Health Service relevance and gives
institutions more information. The requirement applies to anyone responsible
for the design, conduct, or reporting of results.
• The institutions must provide the NIH with more information
than currently required about the value and nature (e.g., equity, travel,
research support) of interests of the principal investigators and key
personnel, and elements of the institution's plan for management of
financial conflicts of interest.
• Institutions must post significant financial conflicts of interest
on a publicly accessible Web site.
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Ms. Paula Polite, Council member and founder and past president of the
Sarcoidosis Research Institute, reported on the 11th Annual NHLBI Public
Interest Organization Meeting held May 24-25, 2010. Ms. Polite thanked
the NHLBI for its continued effort and commitment to the PIOs. She noted
that this year's meeting was exceptional. Representatives from 57 PIO
groups spanning disease areas within the NHLBI mission attended the meeting.
Ms. Polite reported results from an informal survey of meeting participants.
Aspects of the meeting that participants found especially helpful include
opportunities for networking; scientific presentations; information on
NHLBI/NIH process and operation; information about how groups can work
together to increase awareness and promote research; opportunities for
collaborating and exchanging ideas; and opportunities to meet with NHLBI
scientific staff.
Dr. Shurin thanked Dr. Carl Roth, Acting Deputy Director of the NHLBI
and Associate Director for Scientific Program Operation, and his staff
for organizing the meeting each year.
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Dr. George Daley, Professor of Hematology, Director of the Stem Cell
Transplantation Program (Howard Hughes Medical Institute/Children's Hospital,
Boston), and Professor of Biological Chemistry/Molecular Pharmacology
and of Pediatrics at the Harvard Medical School, discussed issues related
to developing and using induced pluripotent stem cells (iPS cells) and
compared them with embryonic stem cells (ES cells).
Stem cells have the remarkable potential to develop into many different
cell types in the body. Moreover, pluripotent stem cells have the ability
to give rise to all the various cell types of the body. For a number of
years, scientists have known how to derive stem cells from human embryos
and grow the cells in the laboratory. More recently, researchers were
able to develop iPS cells by genetically reprogramming adult cells to
an embryonic stem cell–like state. Although such cells meet the
defining criteria for pluripotent stem cells, it is not known if iPS cells
and ES cells differ in significant ways.
Dr. Daley explained the tremendous potential of pluripotent stem cells
in basic research studies of development and gene control; in drug development
and toxicity tests; and for the development of tissues/cells for understanding
and treating disease. A major goal of stem cell research is the ability
to produce customized, patient-specific stem cells.
Dr. Daley is the Principal Investigator on a Recovery Act Grand Opportunities
award to perform functional and molecular comparisons of iPS and ES cells,
comparisons that are essential if the cells are ever to be used to model
disease or as therapies in people. He summarized current knowledge about
iPS cells compared with ES cells:
• iPS and ES cells appear to be functionally similar, but epigenetically
distinct. (Epigenetics refers to changes in the regulation of gene activity
and expression that are not dependent on DNA sequence and can be passed
on during cell division.)
• Many questions remain about the relationship of epigenome variation
to cell behavior.
• Both iPS and ES cells are helpful for modeling disease.
• Improved protocols for reprogramming adult cells into stem
cells are needed.
• Safety issues remain to be defined.
Dr. Daley emphasized that despite the great promise of iPS cells, ES
cells remain extremely valuable research tools.
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Dr. Stephen Mockrin, Director, Division of Extramural Research Activities,
NHLBI, reviewed the Small Business Innovation Research (SBIR) and Small
Business Technology Transfer (STTR) programs. He explained that the SBIR/STTR
set-aside is an underused source of funds for targeted initiatives that
offers substantial opportunities for translating basic science discoveries
into new and better diagnostics and treatments (one of the research opportunities
highlighted by Dr. Francis Collins, Director of the NIH, in Science, January
1, 2010) and also offers economic benefits, such as creating jobs. Congress
is considering phasing in an increase to the SBIR/STTR set-aside.
An NHLBI team, chaired by Dr. Mockrin and Dr. Roth, was charged with
evaluating current best practices and developing strategic approaches
to enhance return on the NHLBI SBIR/STTR investment. Team recommendations
include:
• Develop a dedicated SBIR/STTR office to provide, in a cost-effective
way, critical specialized expertise outside the standard scope of scientific
grant management. (The office will organize and coordinate the recommended
activities itemized below.)
• Increase the NHLBI presence and awareness of its SBIR/STTR
programs within the small business community through strategic outreach
and partnerships.
o Increase the NHLBI SBIR presence at small business and scientific
meetings.
o Partner with state economic development organizations.
o Leverage relevant federal program outreach activities.
• Develop strategic Funding Opportunity Announcements (FOAs).
o Organize working groups to identify medical and scientific opportunities
for commercialization.
o Develop targeted FOAs and small business assistance mechanisms,
including those focused on intramural discoveries.
o Develop strategies to address pre- and post-SBIR funding gaps.
• Enable program outcome evaluations.
Dr. Mockrin provided examples of cutting-edge technologies that could
benefit from targeted initiatives—novel power sources for mechanical
circulatory support devices; early imaging technologies for pulmonary
fibrosis; and point-of-care microassays for blood tests for children and
neonates.
Council members were enthusiastic about the recommendations and offered
several observations and suggestions.
NHLBI staff presented 18 initiatives, all of which had been
reviewed in April by the Board of External Experts (BEE). Initiative development
at the NHLBI is a two-cycle process. Staff within each extramural Division
developed ideas and potential initiatives, which they presented to the
trans-NHLBI Idea Forum. Sufficiently developed initiatives are subsequently
considered by the BEE, which ranks each and provides accompanying advice.
The Council was mostly supportive of the initiatives presented,
but made a number of specific recommendations for consideration prior
to their release. The Acting Director, NHLBI, will consider the recommendations
of the BEE and the Council and other budgetary and programmatic issues
in determining which of the proposed initiatives, if any, to implement.
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Strategic Plan Goal I: To improve understanding of the molecular
and physiological basis of health and disease, and to use that understanding
to develop improved approaches to disease diagnosis, treatment, and prevention:
Anchoring Metabolomic Changes to Phenotype (R01),
RFA
To facilitate metabolomic phenotyping of existing cohorts
and improve understanding about the role of metabolites in the functional
pathways and molecular mechanisms that contribute to the observed phenotype.
Council recommended this initiative.
Etiology and Pathophysiology of Sleep Disordered
Breathing in Pregnancy (R01), PA
To elucidate mechanisms underlying the etiology of sleep
disordered breathing in pregnancy and its pathophysiological association
with gestational heart, lung, and blood diseases.
Council recommended this initiative.
Getting from Genes to Function in Lung Disease (R01),
RFA
To characterize the biological functions of genetic variants
that have been associated with lung diseases.
Council recommended this initiative.
Life After Linkage: The Next Generation of Family
Studies (R01), RFA
To localize and identify rare genetic variants that contribute
to complex heart, lung, blood, and sleep diseases using existing family
studies. Researchers will integrate new, state-of-the-art molecular measures
(such as next-generation sequencing, gene expression, metabolomics, deep
phenotyping, methylation, or copy number variation measures) with existing
genotype and phenotype data to provide a resource for gene discovery and
characterization.
Council recommended this initiative.
Maximizing the Scientific Value of the NHLBI Biologic
Specimen Repository: Scientific Opportunities for Early Stage Investigators
(R21), RFA
To provide early stage investigators with funding, human
biospecimens (housed in the NHLBI Biologic Specimen Repository), and associated
data to conduct research in heart, lung, and blood diseases and blood
resources.
Council recommended this initiative.
Ribosomal Disorders and Their Role in Inherited
Bone Marrow Failure Syndromes (R01), RFA
To extend understanding of the molecular
and cellular mechanisms underlying human disorders of ribosome dysfunction,
their effects on hematopoiesis, and their role in bone marrow failure
syndromes.
Council recommended this initiative.
Sickle Cell Disease: Inflammation, Thrombosis and Vascular Dysfunction
(R01), RFA
To improve understanding of the role of the immune and coagulation systems
in the vaso-occlusive pathologies associated with sickle cell disease
(SCD); to attract cell biologists and vascular biologists to SCD research;
and to identify new targets to improve the therapeutic options for SCD
patients.
Council recommended this initiative.
Sleep Disordered Breathing During Pregnancy and Risks to Cardiovascular
Health (U10), Interagency Agreement
To elucidate the significance of sleep disordered breathing during pregnancy
as a risk to maternal cardiovascular health and related pregnancy outcomes.
The initiative will add measurements of sleep disordered breathing to
an existing large-scale community-based study of cardiovascular disease
risk during pregnancy.
Council recommended this initiative.
Toward an Improved Understanding of HDL Function (R01), RFA
To develop and validate methods to assess high-density lipoprotein (HDL)
function, including identifying and validating biomarkers of HDL function;
and to elucidate HDL functional pathways, including their genetic substrates.
Council recommended this initiative.
Translational Research Centers in Thrombotic and Hemostatic Disorders
(U50), RFA
To accelerate the translation of basic research discoveries to improve
prevention, diagnosis, and treatment of thrombotic and hemostatic disorders.
Each Center will be required to support early-stage translational research
to integrate applied and basic science to move research discoveries toward
clinical application, and to collaborate with the Clinical and Translational
Science Award (CTSA) programs at their institutions (or institutional
programs with similar capabilities) to leverage resources and assist in
navigating regulatory obstacles.
Council recommended this initiative.
Utilization of a Human Lung Tissue Resource for Vascular Research
(R03), RFA
To promote the use of human biospecimens and clinical
data collected by the Pulmonary Hypertension Breakthrough Initiative in
studies to advance knowledge of pulmonary arterial hypertension and other
vascular diseases.
Council recommended this initiative.
Strategic Plan Goal II: To improve understanding
of the clinical mechanisms of disease and thereby enable better prevention,
diagnosis, and treatment:
Consortium of Lung Repair and Regeneration: Building the Foundation
(U01), RFA
To identify molecular and cellular mechanisms of lung repair and regeneration,
and support development of tools, reagents, and model systems to enhance
investigations of such mechanisms.
Council recommended this initiative.
Effects of Secondhand Smoke on Cardiovascular and Pulmonary
Disease Mechanisms (R01), PAR
To improve characterization of the dose-response relationship between
secondhand smoke exposure and cardiovascular and pulmonary diseases by
elucidating the mechanisms by which secondhand smoke contributes to these
diseases. The initiative will support a wide range of research including
laboratory studies, cohort and case-control studies, and natural experiments
resulting from home, workplace, and/or community changes in secondhand
smoke exposure.
Council recommended this initiative.
Pediatric Hydroxyurea Phase III Clinical Trial (Baby HUG): Evaluation
of a Long Term Cohort Treated with Hydroxyurea Early in Life (N01), RFP
To investigate the effects of early intervention with hydroxyurea on
very young children (ages 9-17 months) with sickle cell disease through
the first decade of life; and to evaluate organ function, growth and psychosocial
development, and predictive value of biomarkers in this cohort of children.
The initiative is for a 5-year extension of follow-up (and an additional
9-month data analysis period) of participants in the original BABY HUG
treatment study.)
Council recommended this initiative.
Translation of Pluripotent Stem Cell Therapy for Blood Diseases
(R01), PAR
To encourage development of new technologies that enable the translation
of recent stem cell advances to the treatment of sickle cell disease and
other blood disorders. The initiative focuses on two promising areas:
(1) Development of efficient methods to differentiate human pluripotent
stem cells to hematopoietic stem cells in sufficient numbers and of suitable
quality for clinical evaluation (or, as an alternate strategy, to reprogram
somatic cells to hematopoietic stem cells); (2) Development of protocols
that enable efficient engraftment of hematopoietic stem cells derived
from pluripotent stem cells or from somatic cells and that result in functional
regeneration all blood cell lineages.
Council recommended this initiative.
Strategic Plan Goal III: To generate an improved understanding
of the processes involved in translating research into practice and use
that understanding to enable improvements in public health and to stimulate
further scientific discovery:
Clinical Hematology Research Career Development Program (K12),
RFA
To develop and maintain multidisciplinary career development programs
in clinical hematology research to equip new academic researchers with
the knowledge and skills to address complex problems in blood diseases,
transfusion medicine, and cellular therapies.
Council recommended this initiative.
Development and Testing of a Case Finding Methodology in COPD
(U01), RFA
To design and test a strategy for finding cases of moderate-to-severe
chronic obstructive pulmonary disease (COPD).
Council recommended this initiative.
Research Education in Sleep and Circadian Biology (R25), PAR
To accelerate the transfer of recent scientific advances and health
knowledge in sleep and circadian biology using innovative educational
tools and programs. Individual programs may facilitate team science partnerships;
enhance evidence-based practice among providers; or advance community
awareness through broader public health initiatives.
Council recommended this initiative.
CLOSED PORTION
This portion of the meeting was closed to the public
in accordance with the determination that it concerned matters exempt
from mandatory disclosure under Sections 552b(c)(4) and 552b(c)(6), Title
5, U.S. Code and Section 10(d) of the Federal Advisory Committee Act,
as amended (5 U.S.C. appendix 2).
The session included a discussion of procedures and policies regarding
voting and confidentiality of application materials, committee discussions
and recommendations. Members absented themselves from the meeting during
discussion of and voting on applications from their own institutions,
or other applications in which there was a potential conflict of interest,
real or apparent. Members were asked to sign a statement to this effect.
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The Council considered 1292 applications requesting $1,738,353,922
in total direct costs. The Council recommended 1292 applications with
total direct costs of $1,738,353,922.
The meeting was adjourned at 2:40 p.m.
on May 26, 2010.
ADJOURNMENT
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