National Heart, Lung, and Blood Advisory Council June 2019 Meeting Summary

Bethesda, MD


The 282nd meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) was convened on Tuesday, June 4, 2019 in Building 35A, the Porter Neuroscience Center Conference Center, National Institutes of Health (NIH), Bethesda, Maryland. It was open to the public from 8:10 a.m. until 12:20 p.m. Closed session began at 12:45 p.m. and ended at 2:15 p.m. Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI), presided as Chair.




June 4, 2019

The 282nd meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) was convened on Tuesday, June 4, 2019 in Building 35A, the Porter Neuroscience Center Conference Center, National Institutes of Health (NIH), Bethesda, Maryland. It was open to the public from 8:10 a.m. until 12:20 p.m. Closed session began at 12:45 p.m. and ended at 2:15 p.m. Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI), presided as Chair.

Council Members attending

Dr. Donna K. Arnett
Dr. Jennifer DeVoe
Ms. Grace A. Dorney Koppel
Dr. Martha Gillette
Dr. Karen Glanz
Dr. Garth Graham
Dr. M. Luisa Iruela-Arispe
Dr. Monica Kraft
Dr. Mohandas Narla
Dr. Robert C. Robbins
Dr. Dean Sheppard
Dr. Kim M. Smith-Whitley
Dr. Kevin Thomas
Dr. Sally E. Wenzel

Council Members attending via Teleconference

Dr. Diane J. Nugent
Dr. Andrew S. Weyrich

Council Members unable to attend

Dr. E. Dale Abel
Dr. Richard S. Schofield (ex officio)

NHLBI employees attending

A number of NHLBI staff members were in attendance.

Other NIH Institute employees attending

Dr. Linda Kupfer, Fogarty International Center, NIH

Public attenting

Dr. Paul Avillach, Harvard
Dr. Kira Bradford, Renaissance Computing Institute
Mr. Steve Cox, Renaissance Computing Institute
Dr. Anthony Cristillo, Social & Scientific Systems
Dr. Brandi Davis-Dusenbery, Seven Bridges Genomics
Dr. Zac Flamig, University of Chicago
Ms. Abby George, University of Chicago
Dr. John Greene, Booz Allen Hamilton
Mr. Robert Grossman, University of Chicago
Ms. Sheila Harley, Betah Associates
Dr. Melissa A. Haendel, Oregon State University
Ms. Julie Hayes, University of North Carolina at Chapel Hill
Ms. Melissa King, Westat
Dr. Ashok Krishnamurthy, University of North Carolina at Chapel Hill
Dr. Alison Leaf, Seven Bridges Genomics
Mr. W. Christopher Lenhardt, University of North Carolina at Chapel Hill
Dr. David Mendelson, Mount Sinai
Ms. Joanna Mieczkowska, University of North Carolina at Chapel Hill
Dr. Anthony Philippakis, The Broad Institute
Mr. Andrew Rula, The Broad Institute
Mr. Garrett Rupp, University of Chicago
Ms. Maria Ryan, Decision Lens
Ms. Danielle Troyer, University of Chicago
Mr. Jason Williams, Cold Spring Harbor Laboratory


Dr. Gary H. Gibbons, Director of the National Heart, Lung, and Blood Institute (NHLBI), called the 282nd meeting of the National Heart, Lung, and Blood Advisory Council (NHLBAC) to order and welcomed members and other attendees.


Dr. Laura K. Moen, Director, Division of Extramural Research Activities, NHLBI, made the required announcements for the Council meeting, including the publication of a notice in the Federal Register as well as reminders to Council members regarding conflict of interest and lobbying activities.


NHLBI's Division of Lung Diseases Celebrates 50th Anniversary. Dr. Gibbons recognized this important milestone, which has been celebrated on Capitol Hill and at a National Institutes of Health (NIH) symposium. The NHLBI is building on this legacy by identifying the molecular pathways that drive lung disease progression or promote resilience and repair. Understanding the natural history of lung disease is a key part of the Institute’s portfolio, as are basic and clinical science.

Fiscal Year (FY) 2019 Budget. Because Congress appropriated funds for NIH at the beginning of the current fiscal year, the NHLBI was able to make the transition from FY 2018 to FY 2019 seamlessly. The NHLBI received an increase of approximately $200 million this year. During hearings, congressional appropriations committees discussed several topics that are relevant to the NHLBI’s portfolio, including e-cigarettes, maternal mortality, and health disparities. Negotiations are still underway about the FY 2020 budget for the NIH.

The FY 2019 appropriations has allowed the NHLBI to sustain its R01 success rate, which is 24.2%. Dr. Gibbons explained that although the NHLBI budget has increased by approximately 30% over the last few years, the number of R01 grants the Institute has issued has risen more slowly. The main reason is that the average costs of awards are increasing.

Diversity and Inclusion. Although women account for half of mentored career awardees, only one-third of R01 recipients are women. Some evidence suggests that women have slightly lower NIH award rates than men, but the difference is modest. More striking is that many more men than women submit research program grant (RPG) applications, and fewer women than men apply for R01 renewals. This evidence suggests that the NHLBI may need to do more to support women between their first career development awards and their first R01 award renewals.

However, addressing this gap is not only an NHLBI responsibility, but also requires effort from the entire scientific community. Investigators are only eligible to apply for R01s if they have a faculty position. Although many women have a Ph.D., fewer women hold assistant professor positions than men. The NIH Intramural Research Program has a similar challenge, with gaps in the numbers of female investigators who obtain tenure compared with men. Institutions that conduct research must be diverse and inclusive, especially with the next generation of tenure-track faculty.

Nurturing the Next Generation. The R01 success rate, at almost 33% for early-stage investigators (ESIs) at the NHLBI, has risen steadily in the last few years. The NHLBI is committed to sustaining the robust success rate. ESIs with NHLBI funding include more women and members of underrepresented minority groups than the overall applicant and established investigator pools.

Maternal Morbidity and Mortality. The maternal mortality rate in the United States is higher than in other developed countries and might be rising. Some of the primary drivers of maternal morbidity and mortality are in the NHLBI portfolio, including thromboses, cardiovascular disease, and sleep disorders. The NHLBI is taking a multidisciplinary team science approach to this problem by, for example, leveraging initiatives focused on women’s health, conducting sex- and gender-specific studies, and using existing resources for further discovery.

Data Storage, Toolspace, Access, and analytics for biG-data Empowerment (DataSTAGE). DataSTAGE, the subject of a presentation later in this meeting, will provide a communal, global discovery platform for multidisciplinary open science.


Dr. Jonathan Kaltman, Branch Chief, Heart Development & Structural Diseases Branch, and Director, DataSTAGE Program, at the NHLBI, introduced Dr. Ingrid Borecki, Adjunct Pofessor of Genetics at Washington University School of Medicine in St. Louis and Chair of the DataSTAGE Steering Committee. Dr. Borecki explained that the DataSTAGE mission is to develop and integrate advanced cyberinfrastructure; leading-edge tools; and findable, accessible, interoperable, and reproducible (FAIR) data to support the NHLBI research community. This cloud-based platform provides tools, applications, and workflows that provide these capabilities. Authenticated researchers will be authorized to obtain access to certain data in DataSTAGE based on their research use statement and informed consent from research participants.

Dr. Borecki showed several videos to demonstrate how researchers might interact with DataSTAGE to obtain and analyze data from Chronic Obstructive Pulmonary Disease Genetic Epidemiology (COPDGene), a component of TOPMed. COPDGene’s wealth of lung computed tomography images could be useful for understanding the biological mechanisms influencing COPD heterogeneity and progression. DataSTAGE solutions that can be used to achieve this goal include:

  • Cloud technology that supports big-data storage, computation, and sharing
  • Centralized storage and documentation of data assets with streamlined authorization and access procedures to democratize access
  • Data and platform access and interoperability across data resources and other systems
  • Access to sophisticated tools through point-and-click tools
  • Team science and ability for investigators to bring their own data and tools

DataSTAGE is collecting feedback from a group of alpha users, primarily COPDGene researchers, to refine and expand DataSTAGE. TOPMed researchers will become DataSTAGE beta testers starting in the fall of 2019. Although the program will collect feedback from these investigators, they will be able to conduct analyses that they can use for publications.


Dr. Robert Balaban, Director of NHLBI’s Division of Intramural Research (DIR) introduced this session’s speaker, Dr. Nihal Altan-Bonnet, Senior Investigator and Head of the Laboratory of Host-Pathogen Dynamics at DIR.

Dr. Altan-Bonnet described her laboratory’s discovery of a new form of viral transmission. According to the old paradigm, viral transmission is mediated by freely moving, single virus particles. This paradigm also holds that viral progeny leave cells through a lytic process and travel to other hosts as independent infectious units. The theory is that this form of viral transmission is a very efficient way for viruses to spread to many hosts quickly.

Dr. Altan-Bonnet and her colleagues re-examined this paradigm with several RNA viruses (including poliovirus, enterovirus D68, rhinovirus, and norovirus) using electron microscopy. They found that many large vesicles containing up to 100 poliovirus particles emerged from infected cells. Studies in Dr. Altan-Bonnet’s laboratory and those of others have shown that many RNA and some DNA viruses, including rotaviruses, hepatitis A and C, West Nile, and dengue, travel in clusters inside extracellular vesicles (EVs). In vitro studies showed that the EVs could transfer viruses to other cells. Subsequent studies confirmed that EVs could transfer viruses to other cells from animals and humans.

Dr. Altan-Bonnet’s in vitro studies also showed that the viruses contained in EVs could replicate more efficiently than free viruses. Possible reasons include that while a virus translates and replicates itself in a new cell, the host immune response has time to degrade and dismiss the virus. In addition, viral particles carry many mutations, including some that can slow down translation or replication or make the viruses more vulnerable to host defense.

Dr. Altan-Bonnet and her colleagues are now studying the host immune response to vesicle-cloaked viruses, cellular mechanisms of infection, and the stability of EVs containing virus in treated wastewater.


Title: Generate a Precision Medicine Intergenerational Resource for the Study of Factor VIII Immunogenicity in Severe Hemophilia A (N01)

Objectives: This research initiative has three major aims: 1) to establish a unique, robustly annotated data and biospecimen resource, prospectively derived from a de novo antenatal/neonatal/pediatric cohort with severe hemophilia A, which is immediately accessible to the broader research community at maturity using NIH and NHLBI data and biorepository resources; 2) to use this resource (designed to leverage trans-omics, demographics, phenotypic data, and the potential of in silico modeling) to elucidate novel and targetable mechanisms of immunogenicity and tolerance to factor VIII (FVIII) exposure and to use the mechanistic data to inform robust precision medicine-based models for identifying those at significant risk for developing anti-FVIII antibodies (inhibitors); and 3) to serve the broader NHLBI mission by developing a unique intergenerational biorepository and database interoperable with NHLBI data infrastructure to allow for public use interrogation of other priority DOHaD (Developmental Origins of Health and Disease) questions related to HLBS and developmental disorders.

Title: Sickle Cell Disease in Sub-Saharan Africa Network (SCD in SSA Net) Awards (U24, U01)

Objectives: The proposed initiative will support the continuation and expansion of the Sickle Pan-African Research Consortium (SPARCO) and the Sickle Africa Coordinating Center (SADaCC). It will also provide funding for the development of three new Consortium sites located in additional sub-Saharan African nations. Together, these entities will constitute the Sickle Cell Disease in Sub-Saharan Africa Network (SCD in SSA Net).

Title: Increasing National Awareness of Sickle Cell Disease Challenge (N01)

Objectives: To develop innovative information dissemination tools, instruments, or devices that may be used to increase the public’s awareness of Sickle Cell Disease (SCD). The Challenge also aims to advance the field of implementation science research through training, mentoring, and highlighting the contributions of a new generation of researchers.

Title: Implementation Research to Determine Optimal and Sustainable Strategies to Improve Case Finding, Cascade Screening and Treatment for Familial Hypercholesterolemia (CASCADE-FH) (R61/R33)

Objectives: The objective of this initiative is to develop and test innovative strategies for accelerating the uptake and sustainment of evidence-based detection, diagnosis, and treatment of adults with familial hypercholesterolemia (FH). This initiative will support research studies that explore barriers and facilitators to implementing cascade screening; utilize implementation science methodologies and frameworks to study adoption, sustainability, and scalability of cascade screening programs, and develop innovative approaches to identify high-risk individuals.

Title: Stimulating T4 Implementation Research to Optimize Integration of Proven-effective Interventions for Heart, Lung, and Blood Diseases and Sleep Disorders into Practice (STIMULATE-2) (R61/R33 Clinical Trial Required)

Objectives: The proposed STIMULATE-2, R61/R33 RFA (with clinical trials required) would replace STIMULATE-1, HL-19-014, R01 RFA (clinical trials not allowed). The STIMULATE-2 FOA will enable the applicant community to select high-priority HLBS conditions and feasible evidence-based interventions for the purposes of conducting late-stage T4 translational research (T4TR) to prevent or better manage heart, lung, and blood diseases and sleep disorders (HLBS conditions). This RFA, in part, builds upon NHLBI and NIH supported clinical discoveries, as we extend and enhance the likelihood that evidence-based practices realize their positive impact on health, as needed.

Title: Circadian Patterns of Gene Expression Associated with Disease (R01)

Objectives: Elucidate circadian and rhythmic gene expression profiles associated with disease risk and phenotypes.

Title: Lung Transplant Clinical Research Consortium (LTCRC) (U01)

Objectives: To create a cooperative multi-site clinical research consortium that supports observational studies evaluating lung transplant selection criteria and early clinical management strategies as they relate to the development of primary and acute lung allograft dysfunction. Beyond improving our understanding of factors that influence the incidence of these important post-transplant complications, the harmonization of clinical data and biospecimen collection across lung transplant centers will serve as a critical first step towards standardizing early clinical management and assessment practices in lung transplantation and facilitating future clinical trials to optimize donor lung utilization and improve short- and long-term outcomes for lung transplant recipients.

Title: NHLBI's participation in Methods to Improve Reproducibility of iPSC Derivation, Growth and Differentiation (SBIR) (R44 – Clinical Trial Not Allowed)

Objectives: A variety of issues may affect derivation of the iPSCs and their growth, stability and differentiation, including the specific characteristics of the starting cell or tissue sample (e.g., age of donor, tissue type and anatomical location, physiological and disease state), the methods and protocols used to induce pluripotency (e.g., transcription factors, small molecules, cell fusion), the choice of growth factors and other culture conditions, method of storage of cell lines, etc. Further challenges include growing and maintaining sufficient quantities of iPSC lines in culture without changes in their properties, as well as the ability of multiple investigators to identify and authenticate iPSC lines as part of their research. This FOA addresses the needs of the biomedical research community to improve reproducibility of iPSC derivation, growth and differentiation.

Title: Limited Competition: Small Grant Program for NHLBI K01/K08/K23 Recipients (R03 Clinical Trial Optional)

Objectives: This renewal is for the limited competition Small Grant Research Program (R03) intended to support NHLBI K01, K08, and K23 awardees near the end of their K award to expand their current research objectives and aid them in their transition to independence. The R03 supports research projects that can be carried out in a short period of time with limited resources and that provide or strengthen preliminary data to enhance the capability of mentored K award recipients to conduct research as they strive to complete their transition to independent investigator status.

Title: Secondary Analysis of Existing Datasets in Heart, Lung, and Blood Diseases and Sleep Disorders (R21)

Objectives: This funding opportunity aims to stimulate the use of existing human datasets for well-focused secondary analyses to test innovative hypotheses concerning the epidemiology, pathophysiology, prevention or treatment, and implementation of evidence-base interventions for HLBS diseases/conditions relevant to the NHLBI mission. Analyzing existing datasets provides a cost-effective method to address research questions and generate preliminary data for subsequent research proposals.

Title: Small Research Grants for Analyses of Gabriella Miller Kids First Pediatric Research Data (R03)

Objectives: Catalyze discovery of new genetic variants underlying structural birth defects or childhood cancer by supporting analyses of whole genome sequence datasets that are being generated as part of the Gabriella Miller Kids (Kids First) Pediatric Research Program. Another important goal of the initiative is to generate preliminary data that can be used to support larger, investigator-initiated projects focused on functional studies. This initiative is a renewal of a trans-NIH funding announcement (PAR-16-348), led by NICHD, and involves a partnership of multiple Institutes.

Title: Leveraging the Adolescent Brain and Cognitive Development Cohort (U24)

Objectives: The intent of this proposal is to support novel epidemiologic heart, lung, blood, and sleep (HLBS) research by continuing to co-fund the National Institute of Drug Abuse (NIDA)’s Adolescent Brain Cognitive Development (ABCD) Study during the fourth ABCD cohort examination (2020-2022), at which time participants will be 13-14 years of age. Specifically, this initiative will provide further support for measures relevant to HLBS developmental processes, underlying mechanisms of NHLBI disorders, and relationships with cognitive and brain functioning. Examples include: blood pressure, laboratory studies (total cholesterol, HDL cholesterol, hemoglobin AIC, complete blood count, ferritin, lead level) and survey data (dietary, respiratory, and second-hand smoke). In order to expedite NHLBI related objectives, the proposal will also provide funding for pediatric HLBS epidemiologists.

Title: Secondary participation to the Human Health Exposure Analysis Resource (HHEAR) (U2C)

Objectives: The goal of the Human Health Exposure Analysis Resource is to provide infrastructure for adding or expanding exposure analysis to advance understanding of the impact of environmental exposures on human health throughout the lifecourse.


This portion of the meeting was closed to the public in accordance with the determination that it concerned matters exempt from mandatory disclosures 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.


A report prepared by the Board of Scientific Counselors (BSC), NHLBI, on the NHLBI staff and intramural laboratories was presented to the Council by Dr. Robert Bonow (BSC Member), Northwestern University.


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. The Council considered and recommended 3,082 applications requesting $6,414,719,977 in total costs. For the record, it is noted that secondary applications were also considered en bloc. There were applications considered by early concurrence.


The meeting was adjourned at 2:15 p.m.