NATIONAL HEART, LUNG, AND BLOOD ADVISORY COUNCIL

MEETING MINUTES
October 30, 2007

I. CALL TO ORDER AND OPENING REMARKS - Dr. Elizabeth G. Nabel

Dr. Elizabeth G. Nabel, Director of the National Heart, Lung, and Blood Institute, welcomed members to the 228th meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC).

Member Updates:

Dr. Nabel announced three new Council nominees (final clearance of nominations expected soon):

• Dr. Andrew Marks, Chair of the Department of Physiology and Cellular Biophysics and Clyde and Helen Wu Professor of Molecular Cardiology, College of Physicians and Surgeons, Columbia University
• Dr. C. Noel Bairey Merz, Medical Director, Women's Health Program, Preventive and Rehabilitative Cardiac Center, Cedar-Sinai Medical Center
• Dr. Marlene Rabinovitch, Research Director, Vera Moulton Wall Center for Pulmonary Vascular Diseases, Stanford University School of Medicine

Dr. Nabel welcomed representatives of NHLBI Advisory Committees:

• Dr. Gary Owens and Dr. Ivor Benjamin, representing the NHLBI Board of Scientific Counselors
• Dr. F. Daniel Armstrong, Chair of the Sickle Cell Disease Advisory Committee
• Dr. Phyllis Zee, Chair of the Sleep Disorders Research Advisory Board
• Dr. Louis Dell'Italia, representing the Heart, Lung, and Blood Program Project Review Committee
• Dr. David Guidot, representing the NHLBI Institutional Training Mechanism Review Committee

Dr. Nabel recognized three Council members who are retiring:

• Dr. Roberto Bolli
• Dr. Richard Boucher
• Dr. Robert Lemanske

New Staff:

Dr. Marvin Konstam will join the Institute (on January 1, 2008) as Senior Advisor to the Director, NHLBI, for Cardiovascular Diseases. Dr. Konstam is currently the Chief of Cardiology at Tufts-New England Medical Center and Professor of Medicine and Professor of Radiology at Tufts University School of Medicine.

Invited Guests:

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II. REVIEW OF CONFIDENTIALITY AND CONFLICT OF INTEREST - Dr. Elizabeth G. Nabel

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. A notice of this meeting was published in the Federal Register indicating that it would not be open to the public. Dr. Nabel also reminded the Council members that they are Special Government Employees and are subject to D epartmental conduct regulations.

The session included a discussion of procedures and policies regarding voting and confidentiality of application materials, committee discussions, and recommendations. Members were not present 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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lII. REPORT OF THE DIRECTOR - Dr. Elizabeth G. Nabel

Budget Report:

Despite austere budgetary times, the NHLBI continues to maintain its commitment to new investigators and those in the early stages of their research careers. To this end, in Fiscal Year (FY) 2007, the Institute awarded 182 Research Project Grants (R01 mechanism) to new investigators; 7 first-time R01 renewals to new investigators; 1 NIH Director's New Innovator Award; 18 NIH High Priority, Short-Term Project Awards (Bridge Awards; R56 mechanism); and 24 NIH Pathway to Independence Awards (K99/R00 mechanism).

The Institute is currently operating under a Continuing Resolution, effective through November 16, 2007. Although the Institute's FY 2008 payline is conservative at this time, it is expected to improve as the year progresses. The NHLBI FY 2008 President's Budget (which the Institute developed a year ago and defended to the Congress last Spring) is $2,925,413,000 — a 0.11 percent increase over the Institute's actual FY 2007 budget. Research project grants (RPGs) represent 67.0 percent of the total NHLBI FY 2008 President's Budget. Within that category, the number of noncompeting RPGs is expected to decrease slightly from the FY 2007 level, while the number of competing RPGs is expected to increase slightly.

Updates:

NHLBI Strategic Plan:

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IV. ENHANCING PEER REVIEW AT THE NIH – Dr. Lawrence Tabak

Dr. Lawrence Tabak, Director of the National Institute of Dental and Craniofacial Research and Co-Chair of two NIH Working Groups on Peer Review, summarized recent NIH-led efforts, conducted in partnership with the scientific community, to study the NIH peer review system and determine ways to enhance it. Initially, the NIH issued a Request for Information (RFI) to the scientific community and the public for creative, concrete suggestions on ways to strengthen the system used by the NIH to support research, emphasizing ways to improve the peer review process. A strong response to the RFI was received, and the NIH has since gathered additional information by holding dean's teleconferences and conducting town meetings, soliciting input from NIH staff, and analyzing approaches used by other agencies in the U.S. and abroad. NIH leadership will determine the next steps, which are likely to include pilot studies and associated evaluations of promising approaches.

Many ideas emerged from the study, including innovative ways to improve review criteria, incorporate new models of review, enhance the quality of review and reviewers, modify review mechanics and improve feedback to applicants, modify approaches for scoring applications, and improve other aspects of the system used to support research.

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V. INTEGRATING CELLULAR SYSTEMS IN DIRECTED CELL MIGRATION – Dr. Clare Waterman

Dr. Clare Waterman, Senior Investigator, Cell Biology and Physiology Center, NHLBI Intramural Program, discussed her research related to cell migration. (Cell migration is important in normal biological processes such as development and activities of the immune system, and in pathological conditions such as metastatic cancer and vascular disease.) While at The Scripps Research Institute (prior to joining the NHLBI), Dr. Waterman oversaw the development of a quantitative imaging technology called Fluorescent Speckle Microscopy (FSM), which she is using to investigate the temporal/spatial aspects of cell migration. Dr. Waterman showed data from several experiments using FSM technology to detect and track molecules involved in cell migration. She looks forward to continuing her research at the NIH.

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VI. MEETING OF THE BOARD OF EXTERNAL EXPERTS – Dr. Elizabeth G. Nabel

NHLBI staff presented 11 new initiatives and 5 renewals, all of which had been reviewed in September by the Board of External Experts (BEE). Initiative development at the NHLBI is a two-cycle process. First, staff within each extramural Division develops ideas and potential initiatives, which they present to the trans-NHLBI Idea Forum. Sufficiently developed initiatives are subsequently considered by the BEE, which ranks each and provides accompanying advice.

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VII. PRESENTATION OF INITIATIVES – Dr. Elizabeth G. Nabel

(RFA=Request for Applications) - (RFP=Request for Proposals)

New Initiatives

Asthma Therapy Research Network , RFA

To develop and conduct multiple clinical trials that address the most important management and new treatment questions in asthma.

Council recommended this initiative.

Cardiovascular and Pulmonary Progenitor Cell Biology Consortium , RFA

To establish a consortium of multi-disciplinary hubs to identify and characterize the optimal cardiovascular and pulmonary progenitor cell lineages for basic science, translational, and clinical studies.

Council recommended this initiative .

Translating Discoveries in the Behavioral Sciences to Reduce Obesity and Promote Cardiovascular Health , RFA

To translate findings from basic research on human behavior into more effective clinical, community, and population interventions to reduce obesity and promote cardiovascular health.

Council recommended this initiative.

Integrative Analytical Methods for Large-scale Multi-dimensional Biomarker, Phenotype, and Genotype Data from the Framingham Biomarkers Project (Broad Agency Announcement) , RFP

To build upon the Framingham Biomarkers Project by supporting the design of novel data integration and analysis methods for extensive heterogeneous biological data, and the application of these methods to large population studies. These innovative analytical approaches will seek to model biological mechanisms and disease development processes relevant to the NHLBI mission.

Council recommended this initiative.

 Developmental Origins of Altered Lung Physiology and Immune Function , RFA

To increase understanding about how the pre- and post-natal environments affect the developing lung and immune system at the molecular and cellular levels, resulting in sustained changes in lung physiology and immune function, and in sub-optimal respiratory health and outcomes.

Council recommended this initiative.

 Development and Application of New Technologies to Targeted Genome-wide Resequencing in NHLBI's Well-phenotyped Populations , RFA

To develop and validate efficient, accessible large-scale genome-wide targeted resequencing technology, drawing upon available massively parallel single-molecule DNA sequencing technologies. If successful, the new technology would be applied to NHLBI's well-phenotyped populations in a future phase.

 Council recommended this initiative.

 Circadian-coupled Cellular Function in Heart, Lung, and Blood: Translational Applications to Disease , RFA

To elucidate the molecular basis of self-sustaining daily cycles (circadian) in cellular function and gene expression, define the role of circadian timing in the organization of cellular pathways, and establish a knowledge platform from which new avenues of translational research can be derived on heart, lung, and blood disease pathogenesis.

Council recommended this initiative.

 Immunomodulatory, Inflammatory, and Vasoregulatory Properties of Transfused Red Blood Cells as a Function of Storage Time , RFA

To improve red blood cell transfusion therapies by supporting basic and translational research to identify the molecular and cellular changes that occur during red blood cell unit preparation and storage, and to evaluate the immunomodulatory, inflammatory, and vasoregulatory effects of storage lesion elements on the blood vessel wall, host cells such as pulmonary, endothelial, and hematopoietic cells, and tissue oxygenation.

Council recommended this initiative.

 Multiple-births and Twins Connecting Heredity, Environment, and Disease (MATCHED) Cohort Study , RFA

To establish a cohort of multiple-birth siblings for a rapid-response study of genotype/phenotype correlations, gene-gene and gene-environment interactions, age-specific effects, epigenetic effects, gene copy number effects, and gene expression effects with sufficient phenotype, age, race, sex, geographic, environmental, and lifestyle diversity to support a wide range of scientific inquiry.

 Council recommended this initiative.

 Lung Tissue-based Research Program , RFA

To promote the use of biospecimens and clinical data collected by the Lung Tissue Research Consortium in studies that will correlate lung molecular characteristics with histopathology and the presence, severity, and phenotypic manifestations of interstitial lung diseases and chronic obstructive pulmonary disease (COPD).

 Council recommended this initiative.

 Sodium Nitrite Infusion to Reduce Reperfusion Injury accompanying Percutaneous Coronary Intervention to Treat Acute Anterior Myocardial Infarction , RFP

To conduct a phase II clinical trial to evaluate the effects of intravenous sodium nitrite administration on infarct size and left ventricular remodeling in patients with acute anterior myocardial infarction who undergo percutaneous coronary intervention (PCI).

 Council recommended this initiative.

Initiatives for Renewal

Medical Education for K-12 Teachers and Students (MKITS II) , RFP

To support science education programs in grades K through 12 designed to: (1) provide students with scientific and research experience while they are still undecided about their future education and career choices, and (2) enable teachers to improve exposure to scientific and research experiences in their schools. The program targets minority and disadvantaged students.

Council recommended this initiative.

NHLBI Ancillary Studies in Genetics, Genomics, and Proteomics , RFA or PA

To conduct genetic, genomic, or proteomic studies in ongoing or completed clinical studies related to heart, lung, blood, and sleep diseases and disorders. The initiative expands upon the NHLBI Ancillary Studies in Pharmacogenetics initiative (which ends in FY 2007). Investigators will use samples collected from study participants to examine genetic, genomic, or proteomic influences on complex diseases, psychosocial factors, and individual differences in response to medication treatment.

Council recommended this initiative.

 NHLBI DNA Resequencing and Genotyping Service , RFP

To provide high-volume resequencing and genotyping services to facilitate the identification of genetic components involved in the initiation, progression, and variable outcome of heart, lung, blood, and sleep diseases and disorders.

Council recommended this initiative.

Renewal of the Women's Health Initiative Memory Study (WHIMS) , RFP

To continue the WHIMS Extension study (ancillary study to the Women's Health Initiative trials of hormone therapy) to: (1) enhance statistical power necessary to identify predictors of cognitive health and decline by increasing the total number of cases of cognitive impairment and probable dementia by about 40 percent; (2) perform repeat brain MRI scans; (3) assess the durability of the adverse effects of postmenopausal hormone therapy on cognition observed during the active intervention phase; and (4) serve as a national resource upon which to build ancillary studies in collaboration with the scientific community.

Council recommended this initiative.

The National Health and Nutrition Examination Survey (NHANES), Cardiovascular, Pulmonary, and Sleep Component , RFP

To gather nationally representative data on the prevalence of heart, lung, blood, and sleep disorders and disease, and their risk factors.

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VIII. 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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IX. INTRAMURAL REVIEW

The Council then reviewed reports prepared by the Board of Scientific Counselors, NHLBI, which reviewed the NHLBI intramural laboratories during FY 2007.

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X. REVIEW OF APPLICATIONS

The Council considered 876 applications requesting $1,032,668,750 in total direct costs. The Council recommended 876 applications with total direct costs of $1,031,847,751. A summary of applications by activity code may be found in Attachment B.

ADJOURNMENT

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