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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II. REVIEW OF CONFIDENTIALITY AND CONFLICT OF INTEREST - Dr. Susan B. Shurin

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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III. REPORT OF THE DIRECTOR - Dr. Susan B. Shurin

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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IV. UPDATE ON FINANCIAL CONFLICT OF INTEREST NOTICE OF PROPOSED RULE MAKING - Dr. Susan B. Shurin

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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V. NHLBI PUBLIC INTEREST ORGANIZATION (PIO) MEETING - Ms. Paula Y. Polite

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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VI. PLURIPOTENT STEM CELLS: ARE iPS CELLS EQUAL TO ES CELLS - Dr. George Q. Daley

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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VII. REPORT ON ENHANCING THE NHLBI'S RETURN OF THE SBIR/STTR INVESTMENT TEAM - Dr. Stephen C. Mockrin

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.

VIII. REPORT OF THE BOARD OF EXTERNAL EXPERTS - Dr. Susan B. Shurin

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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IX. PRESENTATION OF INITIATIVES

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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X. REVIEW OF APPLICATIONS

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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